Frequent downregulation of BTB and CNC homology 2 expression in Epstein-Barr virus-positive diffuse large B-cell lymphoma.

PubMed

Noujima-Harada, Mai; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Sakurai, Hiroaki; Igarashi, Kazuhiko; Ito, Etsuro; Nagakita, Keina; Taniguchi, Kohei; Ohnishi, Nobuhiko; Omote, Shizuma; Tabata, Tetsuya; Sato, Yasuharu; Yoshino, Tadashi

2017-05-01

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma subtype, and the Epstein-Barr virus (EBV)-positive subtype of DLBCL is known to show a more aggressive clinical behavior than the EBV-negative one. BTB and CNC homology 2 (BACH2) has been highlighted as a tumor suppressor in hematopoietic malignancies; however, the role of BACH2 in EBV-positive DLBCL is unclear. In the present study, BACH2 expression and its significance were studied in 23 EBV-positive and 43 EBV-negative patient samples. Immunohistochemistry revealed BACH2 downregulation in EBV-positive cases (P < 0.0001), although biallelic deletion of BACH2 was not detected by FISH. Next, we analyzed the contribution of BACH2 negativity to aggressiveness in EBV-positive B-cell lymphomas using FL-18 (EBV-negative) and FL-18-EB cells (FL-18 sister cell line, EBV-positive). In BACH2-transfected FL-18-EB cells, downregulation of phosphorylated transforming growth factor-β-activated kinase 1 (pTAK1) and suppression in p65 nuclear fractions were observed by Western blot analysis contrary to non-transfected FL-18-EB cells. In patient samples, pTAK1 expression and significant nuclear p65, p50, and p52 localization were detected immunohistochemically in BACH2-negative DLBCL (P < 0.0001, P = 0.006, and P = 0.001, respectively), suggesting that BACH2 downregulation contributes to constitutive activation of the nuclear factor-κB pathway through TAK1 phosphorylation in BACH2-negative DLBCL (most EBV-positive cases). Although further molecular and pathological studies are warranted to clarify the detailed mechanisms, downregulation of BACH2 may contribute to constitutive activation of the nuclear factor-κB pathway through TAK1 activation. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

ClinicalTrials.gov

2018-06-11

ALK-Positive Large B-Cell Lymphoma; Atypical Burkitt/Burkitt-Like Lymphoma; Burkitt-Like Lymphoma With 11q Aberration; Diffuse Large B-Cell Lymphoma Activated B-Cell Type; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; EBV-Positive Mucocutaneous Ulcer; High-Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; Human Herpesvirus 8-Positive Neoplastic Cells Present; Intravascular Large B-Cell Lymphoma; Large B-Cell Lymphoma With IRF4 Rearrangement; Plasmablastic Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Primary Effusion Lymphoma; Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Lymphomatoid Granulomatosis; Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Small Intestinal High Grade B-Cell Lymphoma, Not Otherwise Specified; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus.

PubMed

Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S

2016-12-01

We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients. © The Author(s) 2016.

Avelumab, Utomilumab, Rituximab, Ibrutinib, and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma

ClinicalTrials.gov

2018-06-13

CCND1 Positive; CD20 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Inhibition of ZEB1 by miR-200 characterizes Helicobacter pylori-positive gastric diffuse large B-cell lymphoma with a less aggressive behavior.

PubMed

Huang, Wei-Ting; Kuo, Sung-Hsin; Cheng, Ann-Lii; Lin, Chung-Wu

2014-08-01

Primary gastric diffuse large B-cell lymphomas may or may not have a concurrent component of mucosa-associated lymphoid tissue lymphoma. Diffuse large B-cell lymphoma/mucosa-associated lymphoid tissue lymphomas are often associated with Helicobacter pylori (H. pylori) infection, suggesting that the large cells are transformed from mucosa-associated lymphoid tissue lymphomas. In contrast, only limited data are available on the clinical and molecular features of pure gastric diffuse large B-cell lymphomas. In 102 pure gastric diffuse large B-cell lymphomas, we found H. pylori infection in 53% of the cases. H. pylori-positive gastric diffuse large B-cell lymphomas were more likely to present at an earlier stage (73% vs 52% at stage I/II, P=0.03), to achieve complete remission (75% vs 43%, P=0.001), and had a better 5-year disease-free survival rate (73% vs 29%, P<0.001) than H. pylori-negative gastric diffuse large B-cell lymphomas. Through genome-wide expression profiles of both miRNAs and mRNAs in nine H. pylori-positive and nine H. pylori-negative gastric diffuse large B-cell lymphomas, we identified inhibition of ZEB1 (zinc-finger E-box-binding homeobox 1) by miR-200 in H. pylori-positive gastric diffuse large B-cell lymphomas. ZEB1, a transcription factor for marginal zone B cells, can suppress BCL6, the master transcription factor for germinal center B cells. In 30 H. pylori-positive and 30 H. pylori-negative gastric diffuse large B-cell lymphomas, we confirmed that H. pylori-positive gastric diffuse large B-cell lymphomas had higher levels of miR-200 by qRT-PCR, and lower levels of ZEB1 and higher levels of BCL6 using immunohistochemistry. As BCL6 is a known predictor of a better prognosis in gastric diffuse large B-cell lymphomas, our data demonstrate that inhibition of ZEB1 by miR-200, with secondary increase in BCL6, is a molecular event that characterizes H. pylori-positive gastric diffuse large B-cell lymphomas with a less aggressive behavior.

Onalespib in Treating Patients With Relapsed or Refractory Anaplastic Large Cell Lymphoma, Mantle Cell Lymphoma, or Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2018-05-23

ALK Positive; BCL6 Positive; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma

Carfilzomib, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Stage I-IV Diffuse Large B-cell Lymphoma

ClinicalTrials.gov

2018-03-28

CD20 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Stage I Diffuse Large B-Cell Lymphoma; Stage II Diffuse Large B-Cell Lymphoma; Stage III Diffuse Large B-Cell Lymphoma; Stage IV Diffuse Large B-Cell Lymphoma

Correlation of human papilloma virus status with quantitative perfusion/diffusion/metabolic imaging parameters in the oral cavity and oropharyngeal squamous cell carcinoma: comparison of primary tumour sites and metastatic lymph nodes.

PubMed

Han, M; Lee, S J; Lee, D; Kim, S Y; Choi, J W

2018-05-17

To investigate the differences in perfusion/diffusion/metabolic imaging parameters according to human papilloma virus (HPV) status in the oral cavity and oropharyngeal squamous cell carcinoma (OC-OPSCC), separately in primary tumour sites and metastatic lymph nodes. This retrospective study comprised 41 patients with primary OC-OPSCCs and 29 patients with metastatic lymph nodes. The perfusion/diffusion/metabolic imaging parameters were measured at the primary tumour and the largest ipsilateral metastatic lymph node. The quantitative parameters were compared between the HPV-positive and -negative groups. The HPV-positivity was 39% (16 patients) for the primary tumours and 51.7% (15 patients) for the metastatic lymph nodes. Patients with HPV-positive tumours had a lower T stage (p=0.034). The metastatic lymph nodes for the HPV-positive patients were bulkier (p=0.016) and more frequently had cystic morphology (p=0.005). The perfusion parameters were not different, regardless of HPV status. The diffusion parameter (ADC min , p=0.011) of the metastatic lymph nodes in the HPV-positive groups was lower and metabolic parameter (metabolic tumour volume p=0.035 and total lesion glycolysis p=0.037) were higher than those in HPV-negative groups. The diffusion and metabolic parameters of metastatic lymph nodes from OC-OPSCC were different according to HPV status. The perfusion parameters did not clearly represent HPV status. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Purification and crystallization of Kokobera virus helicase

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Colibus, Luigi; Speroni, Silvia; Coutard, Bruno

2007-03-01

Kokobera virus is a mosquito-borne flavivirus belonging, like West Nile virus, to the Japanese encephalitis virus serocomplex. Crystals of the Kokobera virus helicase domain were obtained by the hanging-drop vapour-diffusion method and exhibit a diffraction limit of 2.3 Å. Kokobera virus is a mosquito-borne flavivirus belonging, like West Nile virus, to the Japanese encephalitis virus serocomplex. The flavivirus genus is characterized by a positive-sense single-stranded RNA genome. The unique open reading frame of the viral RNA is transcribed and translated as a single polyprotein which is post-translationally cleaved to yield three structural and seven nonstructural proteins, one of which ismore » the NS3 gene that encodes a C-terminal helicase domain consisting of 431 amino acids. Helicase inhibitors are potential antiviral drugs as the helicase is essential to viral replication. Crystals of the Kokobera virus helicase domain were obtained by the hanging-drop vapour-diffusion method. The crystals belong to space group P3{sub 1}21 (or P3{sub 2}21), with unit-cell parameters a = 88.6, c = 138.6 Å, and exhibit a diffraction limit of 2.3 Å.« less

Epstein–Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8–9 September 2008

PubMed Central

Cohen, J. I.; Kimura, H.; Nakamura, S.; Ko, Y.-H.; Jaffe, E. S.

2009-01-01

Background: Recently novel Epstein–Barr virus (EBV) lymphoproliferative diseases (LPDs) have been identified in non-immunocompromised hosts, both in Asia and Western countries. These include aggressive T-cell and NK-cell LPDs often subsumed under the heading of chronic active Epstein–Barr virus (CAEBV) infection and EBV-driven B-cell LPDs mainly affecting the elderly. Design: To better define the pathogenesis, classification, and treatment of these disorders, participants from Asia, The Americas, Europe, and Australia presented clinical and experimental data at an international meeting. Results: The term systemic EBV-positive T-cell LPD, as adopted by the WHO classification, is preferred as a pathological classification over CAEBV (the favored clinical term) for those cases that are clonal. The disease has an aggressive clinical course, but may arise in the background of CAEBV. Hydroa vacciniforme (HV) and HV-like lymphoma represent a spectrum of clonal EBV-positive T-cell LPDs, which have a more protracted clinical course; spontaneous regression may occur in adult life. Severe mosquito bite allergy is a related syndrome usually of NK cell origin. Immune senescence in the elderly is associated with both reactive and neoplastic EBV-driven LPDs, including EBV-positive diffuse large B-cell lymphomas. Conclusion: The participants proposed an international consortium to facilitate further clinical and biological studies of novel EBV-driven LPDs. PMID:19515747

Epstein-Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8-9 September 2008.

PubMed

Cohen, J I; Kimura, H; Nakamura, S; Ko, Y-H; Jaffe, E S

2009-09-01

Recently novel Epstein-Barr virus (EBV) lymphoproliferative diseases (LPDs) have been identified in non-immunocompromised hosts, both in Asia and Western countries. These include aggressive T-cell and NK-cell LPDs often subsumed under the heading of chronic active Epstein-Barr virus (CAEBV) infection and EBV-driven B-cell LPDs mainly affecting the elderly. To better define the pathogenesis, classification, and treatment of these disorders, participants from Asia, The Americas, Europe, and Australia presented clinical and experimental data at an international meeting. The term systemic EBV-positive T-cell LPD, as adopted by the WHO classification, is preferred as a pathological classification over CAEBV (the favored clinical term) for those cases that are clonal. The disease has an aggressive clinical course, but may arise in the background of CAEBV. Hydroa vacciniforme (HV) and HV-like lymphoma represent a spectrum of clonal EBV-positive T-cell LPDs, which have a more protracted clinical course; spontaneous regression may occur in adult life. Severe mosquito bite allergy is a related syndrome usually of NK cell origin. Immune senescence in the elderly is associated with both reactive and neoplastic EBV-driven LPDs, including EBV-positive diffuse large B-cell lymphomas. The participants proposed an international consortium to facilitate further clinical and biological studies of novel EBV-driven LPDs.

Association between simian virus 40 and non-Hodgkin lymphoma

NASA Technical Reports Server (NTRS)

Vilchez, Regis A.; Madden, Charles R.; Kozinetz, Claudia A.; Halvorson, Steven J.; White, Zoe S.; Jorgensen, Jeffrey L.; Finch, Chris J.; Butel, Janet S.

2002-01-01

BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.

BK-virus nephropathy and simultaneous C4d positive staining in renal allografts.

PubMed

Honsová, E; Lodererová, A; Viklický, O; Boucek, P

2005-10-01

The role of antibodies in rejection of transplanted kidneys was the subject of debate at the last two Banff meetings and in medical journals. Diffuse C4d positive staining of peritubular capillaries (PTCs) was recognized as a marker of antibody-mediated rejection and this morphological feature was included in the updated Banff schema. At the same time polyomavirus infection of the renal allografts has been reported more frequently and is emerging as an important cause of renal allograft dysfunction and graft loss. At the present time, BK-virus nephropathy (BKN) represents the most common viral disease affecting renal allografts. BKN was identified in 6 patients in 12 biopsies and 2 graft nephrectomy specimens of 1115 biopsies between September 2000 and December 2003. Definite virus identification was done by immunohistochemistry. The reason for graft nephrectomies was graft failure due to BKN in a recipient after kidney-pancreas transplantation with good function of his pancreas graft and the necessity of continuing immunosuppression. Detection of C4d deposits was performed by immunofluorescence or by immunohistochemistry. In graftectomy samples C4d detection was performed by immunohistochemistry and retrospectively in all cases of BKN. Focal C4d positive PTCs and BKN were found simultaneously in 9 of 12 needle biopsies and in both graft nephrectomy samples. Detection of C4d by immunohistochemistry disclosed focal C4d positive staining in kidney tissue but diffuse in the sites where BK-virus inclusions in tubular epithelial cells were found. The complement system is part of the host defense response and is crucial to our natural ability to ward off infection. In cases of BKN, virus likely gains access to the bloodstream through injured tubular walls and via PTCs. Vascular endothelium in the PTCs represents a potential target antigen for alloresponse, and simultaneously possibly represents an imprint of complement activation or complement production in the places with BK-virus infection.

L-asparaginase induced complete remission in Epstein-Barr virus positive, multidrug resistant, cutaneous T-cell lymphoma.

PubMed

Obama, K; Tara, M; Niina, K

1999-06-01

A 30-year-old man was admitted to our hospital with subcutaneous tumors and a high fever. Based on biomicroscopic findings of the tumor, the patient was diagnosed as having diffuse, medium, well-differentiated malignant lymphoma. Immunochemical analysis showed that CD3, CD4, CD25, and TCR beta were positive, and in situ hybridization revealed Epstein-Barr virus-encoded small RNAs in the nuclei of the lymphoma cells. Despite the patient's resistance to multidrug therapy, complete remission was achieved using L-asparaginase. This case is unique because of its peculiar clinical course and a possible association with the Epstein-Barr virus. L-asparaginase may be an important treatment in other patients who exhibit some of these characteristics.

Prevalence and clinicopathologic features of CD30-positive de novo diffuse large B-cell lymphoma in Chinese patients: a retrospective study of 232 cases

PubMed Central

Gong, Qi-Xing; Lu, Ting-Xun; Liu, Chong; Wang, Zhen; Liang, Jin-Hua; Xu, Wei; Li, Jian-Yong; Zhang, Zhi-Hong; Chen, Qi

2015-01-01

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease that great efforts had been made in to build up molecular and immunophenotypic subgroups that could relatively accurate indicate prognosis and give clue to therapy. Recently, CD30 was reported as a useful predictor with favorable clinical outcome. However, CD30 expression patterns and the clinicopathologic features of CD30 positive DLBCL are not well described thus far, especially in Asian patients. Here, we studied 232 cases of de novo DLBCL in East China to investigate the prevalence and clinicopathological features of CD30-positive DLBCL using a panel of immunohistochemical markers. Applying a >0% threshold, CD30 was expressed in approximately 12% patients with Epstein-Barr virus (EBV) negative DLBCL, affecting younger people and showing a lower frequency of BCL2 expression and MYC/BCL2 co-expression. Patients with CD30-positive DLBCLs showed better progression-free survival and overall survival compared with patients with CD30-negative DLBCLs, although the superior outcome of CD30 positivity had minimal effects on BCL2+ DLBCL or DLBCL with MYC/BCL2 co-expression. Moreover, CD30 could express in CD5+ DLBCL. We concluded that CD30 may be useful as a prognostic marker in rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treated DLBCLs, indicating favorable outcomes in a Chinese population. Further studies with larger samples should be performed to investigate the function of CD30 expression in BCL2+ DLBCLs, DLBCLs with MYC/BCL2 co-expression, and CD5+ DLBCLs, and to evaluate the feasibility of anti-CD30 targeted treatment in DLBCL therapy. PMID:26884853

R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2018-06-25

CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

Chromatin organization regulates viral egress dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aho, Vesa; Myllys, Markko; Ruokolainen, Visa

Various types of DNA viruses are known to elicit the formation of a large nuclear viral replication compartment and marginalization of the cell chromatin. We used three-dimensional soft x-ray tomography, confocal and electron microscopy, combined with numerical modelling of capsid diffusion to analyse the molecular organization of chromatin in herpes simplex virus 1 infection and its effect on the transport of progeny viral capsids to the nuclear envelope. Our data showed that the formation of the viral replication compartment at late infection resulted in the enrichment of heterochromatin in the nuclear periphery accompanied by the compaction of chromatin. Random walkmore » modelling of herpes simplex virus 1–sized particles in a three-dimensional soft x-ray tomography reconstruction of an infected cell nucleus demonstrated that the peripheral, compacted chromatin restricts viral capsid diffusion, but due to interchromatin channels capsids are able to reach the nuclear envelope, the site of their nuclear egress.« less

Chromatin organization regulates viral egress dynamics

DOE PAGES

Aho, Vesa; Myllys, Markko; Ruokolainen, Visa; ...

2017-06-16

Various types of DNA viruses are known to elicit the formation of a large nuclear viral replication compartment and marginalization of the cell chromatin. We used three-dimensional soft x-ray tomography, confocal and electron microscopy, combined with numerical modelling of capsid diffusion to analyse the molecular organization of chromatin in herpes simplex virus 1 infection and its effect on the transport of progeny viral capsids to the nuclear envelope. Our data showed that the formation of the viral replication compartment at late infection resulted in the enrichment of heterochromatin in the nuclear periphery accompanied by the compaction of chromatin. Random walkmore » modelling of herpes simplex virus 1–sized particles in a three-dimensional soft x-ray tomography reconstruction of an infected cell nucleus demonstrated that the peripheral, compacted chromatin restricts viral capsid diffusion, but due to interchromatin channels capsids are able to reach the nuclear envelope, the site of their nuclear egress.« less

Vorinostat and Combination Chemotherapy With Rituximab in Treating Patients With HIV-Related Diffuse Large B-Cell Non-Hodgkin Lymphoma or Other Aggressive B-Cell Lymphomas

ClinicalTrials.gov

2018-06-07

AIDS-Related Plasmablastic Lymphoma; AIDS-Related Primary Effusion Lymphoma; CD20 Positive; HIV Infection; Plasmablastic Lymphoma; Primary Effusion Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Stage I Diffuse Large B-Cell Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage II Diffuse Large B-Cell Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage III Diffuse Large B-Cell Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Diffuse Large B-Cell Lymphoma; Stage IV Grade 3 Follicular Lymphoma

Intracellular Transport of Plant Viruses: Finding the Door out of the Cell

PubMed Central

Schoelz, James E.; Harries, Phillip A.; Nelson, Richard S.

2011-01-01

Plant viruses are a class of plant pathogens that specialize in movement from cell to cell. As part of their arsenal for infection of plants, every virus encodes a movement protein (MP), a protein dedicated to enlarging the pore size of plasmodesmata (PD) and actively transporting the viral nucleic acid into the adjacent cell. As our knowledge of intercellular transport has increased, it has become apparent that viruses must also use an active mechanism to target the virus from their site of replication within the cell to the PD. Just as viruses are too large to fit through an unmodified plasmodesma, they are also too large to be freely diffused through the cytoplasm of the cell. Evidence has accumulated now for the involvement of other categories of viral proteins in intracellular movement in addition to the MP, including viral proteins originally associated with replication or gene expression. In this review, we will discuss the strategies that viruses use for intracellular movement from the replication site to the PD, in particular focusing on the role of host membranes for intracellular transport and the coordinated interactions between virus proteins within cells that are necessary for successful virus spread. PMID:21896501

JCAR014 and Durvalumab in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-02

BCL2 Gene Rearrangement; BCL6 Gene Rearrangement; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; High-Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; MYC Gene Rearrangement; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

DETECTION BY PCR OF HUMAN ENTERIC VIRUSES CONCENTRATED FROM LARGE VOLUMES OF WATER

EPA Science Inventory

Viruses are recovered and concentrated from water by passage through a positively charged cartridge filter. Following virus elution from the cartridge filter with beef extract and concentration of the beef extract solution, viruses are usually assayed by cell culture. However...

Using tobacco mosaic virus to probe enhanced surface diffusion of molecular glasses.

PubMed

Zhang, Yue; Potter, Richard; Zhang, William; Fakhraai, Zahra

2016-11-09

Recent studies have shown that diffusion on the surface of organic glasses can be many orders of magnitude faster than bulk diffusion. Developing new probes that can readily measure surface diffusion can help study the effect of parameters such as chemical structure, intermolecular interaction, molecules' shape and size on the enhanced surface diffusion. In this study, we develop a novel probe that significantly simplifies these types of studies. Tobacco mosaic virus (TMV) is used as probe particle to measure surface diffusion coefficient of molecular glass N,N'-bis(3-methylphenyl)-N,N'-diphenylbenzidine (TPD). The evolution of the meniscus formed around TMV is probed as a function of time at various temperatures. TMV has a well-defined, mono-dispersed, cylindrical shape, with a large aspect-ratio (average diameter of 16.6 nm, length of 300 nm). As such, the shape of the meniscus around the center of TMV is semi-two dimensional, which compared to using a nanosphere as probe, increases the driving force for meniscus formation and simplifies the analysis of surface diffusion. We show that under these conditions, after a short transient time the shape of the meniscus is self-similar, allowing accurate determination of the surface diffusion coefficient. Measurements at various temperatures are then performed to investigate the temperature dependence of the surface diffusion coefficient. It is found that surface diffusion is greatly enhanced in TPD and has a lower activation barrier compared to the bulk counterpart. These observations are consistent with previous studies of surface diffusion on molecular glasses, demonstrating the accuracy of this method.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reiss, T.F.; Golden, J.

Pneumocystis carinii pneumonia was suggested by a diffuse, bilateral pulmonary uptake of gallium-67 in an asymptomatic, homosexual male with the antibody to the immunodeficiency virus (HIV) who was undergoing staging evaluation for lymphoma clinically localized to a left inguinal lymph node. Chest radiograph and pulmonary function evaluation, including lung volumes, diffusing capacity and arterial blood gases, were within normal limits. Bronchoalveolar lavage revealed Pneumocystis carinii organisms. In this asymptomatic, HIV-positive patient, active alveolar infection, evidenced by abnormal gallium-67 scanning, predated pulmonary physiologic abnormalities. This observation raises questions concerning the natural history of this disease process and the specificity of physiologicmore » tests for excluding disease. It also has implications for the treatment of neoplasia in the HIV-positive patient population.« less

Lack of detection of feline leukemia and feline sarcoma viruses in diffuse iris melanomas of cats by immunohistochemistry and polymerase chain reaction.

PubMed

Cullen, Cheryl L; Haines, Deborah M; Jackson, Marion L; Grahn, Bruce H

2002-07-01

Diffuse iris melanoma was confirmed by light-microscopic examination in 10 formalin-fixed, paraffin-embedded globes from 10 cats. To determine if feline leukemia virus or a replication defective feline leukemia virus, feline sarcoma virus, was present in these anterior uveal melanomas, immunohistochemistry and polymerase chain reaction for feline leukemia virus were utilized. Immunohistochemical staining for feline leukemia virus glycoprotein 70 was performed on all 10 tumors using an avidin-biotin complex technique. The DNA was extracted from each specimen and a 166-base pair region of the feline leukemia virus long terminal repeat was targeted by polymerase chain reaction. Immunohistochemical staining for feline leukemia virus glycoprotein 70 and polymerase chain reaction amplification of a feline leukemia virus long terminal repeat region were negative in all cases. Feline leukemia virus/feline sarcoma virus was not detected in any neoplasms and therefore was unlikely to play a role in the tumorigenesis of these feline diffuse iris melanomas.

Tyzzer's disease in a red panda (Ailurus fulgens fulgens).

PubMed

Langan, J; Bemis, D; Harbo, S; Pollock, C; Schumacher, J

2000-12-01

A debilitated 9-yr-old female red panda (Ailurus fulgens fulgens) with a recent history of corticosteroid administration displayed anorexia, depression, and diarrhea for 2 days. Blood work revealed a moderate nonregenerative anemia, leukocytosis, hypokalemia, hyperbilirubinemia, and mildly elevated alanine aminotransferase and aspartate aminotransferase. Serology was negative for occult heartworm, Toxoplasma gondii, feline leukemia virus, feline infectious peritonitis, feline immunodeficiency virus, and canine distemper virus. Electron microscopy of the feces demonstrated corona-like virus particles. The panda died 3 days after initial presentation. Histologic findings included multifocal, acute, hepatic necrosis and diffuse, necrotizing colitis. Liver and colon lesions contained intracellular, curved, spore-forming, gram-negative, silver-positive rods morphologically consistent with Clostridium piliforme. This panda most likely contracted Tyzzer's disease subsequent to having a compromised immune system after corticosteroid administration and concurrent disease.

From human behavior to the spread of mobile phone viruses

NASA Astrophysics Data System (ADS)

Wang, Pu

Percolation theory was initiated some 50 years ago as a mathematical framework for the study of random physical processes such as the flow of a fluid through a disordered porous medium. It has been proved to be a remarkably rich theory, with applications from thermodynamic phase transitions to complex networks. In this dissertation percolation theory is used to study the diffusion process of mobile phone viruses. Some methodologies widely used in statistical physics are also applied to uncover the underlying statistical laws of human behavior and simulate the spread of mobile phone viruses in a large population. I find that while Bluetooth viruses can reach all susceptible handsets with time, they spread slowly due to human mobility, offering ample opportunities to deploy antiviral software. In contrast, viruses utilizing multimedia messaging services (MMS) could infect all users in hours, but currently a phase transition on the underlying call graph limits them to only a small fraction of the susceptible users. These results explain the lack of a major mobile virus breakout so far and predict that once a mobile operating system's market share reaches the phase transition point, viruses will pose a serious threat to mobile communications. These studies show how the large datasets and tools of statistical physics can be used to study some specific and important problems, such as the spread of mobile phone viruses.

Concurrent detection of herpes simplex and varicella-zoster viruses by polymerase chain reaction from the same anatomic location.

PubMed

Dhiman, Neelam; Wright, Patricia A; Espy, Mark J; Schneider, Susan K; Smith, Thomas F; Pritt, Bobbi S

2011-08-01

Herpes simplex virus (HSV) and varicella-zoster virus (VZV) may cause latent infection of the same peripheral nerve ganglia. However, there are no large studies addressing the frequency of concurrent HSV/VZV PCR positivity from the same anatomic location. In an eight-year retrospective study, we observed 1.3% dual positivity from dermal, genital, and oral mucosal sources. Copyright © 2011 Elsevier Inc. All rights reserved.

Varieties of charge distributions in coat proteins of ssRNA+  viruses

NASA Astrophysics Data System (ADS)

Lošdorfer Božič, Anže; Podgornik, Rudolf

2018-01-01

A major part of the interactions involved in the assembly and stability of icosahedral, positive-sense single-stranded RNA (ssRNA+) viruses is electrostatic in nature, as can be inferred from the strong pH- and salt-dependence of their assembly phase diagrams. Electrostatic interactions do not act only between the capsid coat proteins (CPs), but just as often provide a significant contribution to the interactions of the CPs with the genomic RNA, mediated to a large extent by positively charged, flexible N-terminal tails of the CPs. In this work, we provide two clear and complementary definitions of an N-terminal tail of a protein, and use them to extract the tail sequences of a large number of CPs of ssRNA+  viruses. We examine the pH-dependent interplay of charge on both tails and CPs alike, and show that—in contrast to the charge on the CPs—the net positive charge on the N-tails persists even to very basic pH values. In addition, we note a limit to the length of the wild-type genomes of those viruses which utilize positively charged tails, when compared to viruses without charged tails and similar capsid size. At the same time, we observe no clear connection between the charge on the N-tails and the genome lengths of the viruses included in our study.

Lenalidomide and Blinatumomab in Treating Patients With Relapsed Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-06-11

CD19 Positive; Mediastinal Lymphoma; Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Small Lymphocytic Lymphoma

Lymphomas in Ile-Ife, Nigeria: Immunohistochemical Characterization and Detection of Epstein-Barr virus Encoded RNA.

PubMed

Onwubuya, Ifeyinwa M; Adelusola, Kayode A; Durosinmi, Muheez A; Sabageh, Donatus; Ezike, Kevin N

2015-06-01

The proper histopathological characterization of malignant lymphomas requires the use of immunohistochemistry along with other molecular pathology techniques. Malignant lymphomas histologically diagnosed in our hospital were reclassified according to the WHO scheme using immunohistochemistry while in-situ hybridization was performed for the detection of Epstein-Barr virus encoded RNA. There were 83 cases of lymphoma. The male to female ratio was 1.9:1 while the overall mean age was 41.7 years. Non-Hodgkin lymphomas (NHL) constituted about 79.5% of cases. The majority of cases (98.8%) were B-cell lymphomas. Nine subtypes of lymphomas were identified with diffuse large B-cell lymphomas (56.4% of which were of the germinal centre type) constituting the largest group (47.0%). Intermediate and high grade subtypes were more common. The majority of cases (72.3%) were nodal lymphomas with cervical lymph node being the commonest site (48.2%). Only classical Hodgkin lymphoma (HL) (20.5%) was seen of which the mixed cellularity subtype was the most common. Epstein Barr virus (EBV) encoded ribonucleic acid was detected in 7 cases (8.4%) including 4 cases of HL, 2 cases of Burkitt lymphoma and the only case of plasmablastic lymphoma. About five cases were reclassified as non-lymphoid malignant lesions. Immunohistochemistry is vital to the proper classification of lymphomas even in a resource poor environment. Although nine subtypes of lymphomas were identified, diffuse large B-cell lymphomas formed the largest single group. Epstein-Barr virus probably plays an important role in lymphomatogenesis in this environment. A larger multicentre study is required to prove this.

Mathematical Modeling of Herpes Simplex Virus Distribution in Solid Tumors: Implications for Cancer Gene Therapy

PubMed Central

Mok, Wilson; Stylianopoulos, Triantafyllos; Boucher, Yves; Jain, Rakesh K.

2010-01-01

Purpose Although oncolytic viral vectors show promise for the treatment of various cancers, ineffective initial distribution and propagation throughout the tumor mass often limit the therapeutic response. A mathematical model is developed to describe the spread of herpes simplex virus from the initial injection site. Experimental Design The tumor is modeled as a sphere of radius R. The model incorporates reversible binding, interstitial diffusion, viral degradation, and internalization and physiologic parameters. Three species are considered as follows: free interstitial virus, virus bound to cell surfaces, and internalized virus. Results This analysis reveals that both rapid binding and internalization as well as hindered diffusion contain the virus to the initial injection volume, with negligible spread to the surrounding tissue. Unfortunately, increasing the dose to saturate receptors and promote diffusion throughout the tumor is not a viable option: the concentration necessary would likely compromise safety. However, targeted modifications to the virus that decrease the binding affinity have the potential to increase the number of infected cells by 1.5-fold or more. An increase in the effective diffusion coefficient can result in similar gains. Conclusions This analysis suggests criteria by which the potential response of a tumor to oncolytic herpes simplex virus therapy can be assessed. Furthermore, it reveals the potential of modifications to the vector delivery method, physicochemical properties of the virus, and tumor extracellular matrix composition to enhance efficacy. PMID:19318482

The School's Response to the HIV/AIDS Epidemic: One State's Data.

ERIC Educational Resources Information Center

Newman, Ian M.

The diffusion and adoption of new knowledge is an important outcome of education. This study used the results of two annual cross sectional surveys in a largely rural state, Nebraska, one of school administrators and one of students. The purpose of the survey was to identify how widespread Human Immunodeficiency Virus (HIV)/Acquired Immune…

huJCAR014 CAR-T Cells in Treating Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2018-05-25

Adult B Acute Lymphoblastic Leukemia; BCL2 Gene Rearrangement; BCL6 Gene Rearrangement; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; MYC Gene Rearrangement; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Adult Acute Lymphoblastic Leukemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

Analysis of human papilloma virus in oral squamous cell carcinoma using p16: An immunohistochemical study

PubMed Central

Patil, S.; Rao, R. S.; Amrutha, N.; Sanketh, D. S.

2014-01-01

Aims: The aim of this study is to evaluate the expression of human papilloma virus (HPV) in oral squamous cell carcinoma (OSCC) and to correlate the association of HPV in histological grades of OSCC using p16 (p16INK4a) immunohistochemistry (IHC). Subjects and Methods: This study consists of 30 histological diagnosed cases of OSCC (10-well-differentiated oral squamous cell carcinoma [WDOSCC], 10-moderately differentiated oral squamous cell carcinoma [MDOSCC] and 10-poorly differentiated oral squamous cell carcinoma [PDOSCC]). The sections were subjected to IHC procedure using p16. Two parameters in immunohistochemical p16 expression were evaluated by 3 observers based on the criteria by Galgano M. Tetal (2010) (a) percentage of p16 positive cases (b) pattern of p16 staining in various grades of OSCC. Statistical Analysis Used: Kappa test. Results: Totally, 30 samples of 0SCC, p16 positivity was noted in 26/30 (86.66%). Of 26 positive cases, p16 staining was positive in 7/10 (70%) of WDOSCC, 9/10 (90%) in MDOSCC and, 10/10 (100%) PDOSCC. Incidentally, we also found single dispersed cell staining in WDOSCC, patchy staining in MDOSCC and more diffuse staining pattern predominant in PDOSCC. Conclusions: Our study revealed an association between HPV and OSCC. Diffuse staining pattern was noted in PDOSCC, which in turn depicts the increase viral overload, which might have an influence on its aggressive behavior. PMID:24818098

Clinical report: Detection and management of bovine viral diarrhea virus Type 1b in a large dairy herd

USDA-ARS?s Scientific Manuscript database

Case Description: 1,081 newborn calves from a commercial dairy were tested for bovine viral diarrhea virus antigen by pooled RT-PCR as part of a screening program. Ear tissue from twenty six calves initially tested positive and 14 confirmed positive with antigen capture ELISA two weeks later (1.3...

EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts

PubMed Central

Fend, Falko

2018-01-01

The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders (LPD) of B, T or natural killer (NK) cell type has resulted in the recognition of new entities like EBV+ mucocutaneous ulcer or the addition of chronic active EBV (CAEBV) infection in the revised 2016 World Health Organization (WHO) lymphoma classification. In this article, we review the definitions, morphology, pathogenesis, and evolving concepts of the various EBV-associated disorders including EBV+ diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), EBV+ mucocutaneous ulcer, DLBCL associated with chronic inflammation, fibrin-associated DLBCL, lymphomatoid granulomatosis, the EBV+ T and NK-cell LPD of childhood, aggressive NK leukaemia, extranodal NK/T-cell lymphoma, nasal type, and the new provisional entity of primary EBV+ nodal T- or NK-cell lymphoma. The current knowledge regarding the pathogenesis of B-cell lymphomas that can be EBV-associated including Burkitt lymphoma, plasmablastic lymphoma and classic Hodgkin lymphoma will be also explored. PMID:29518976

An Aggressive Plasmablastic Lymphoma of the Oral Cavity as Primary Manifestation of Acquired Immunodeficiency Syndrome: Case Report and Literature Review

PubMed Central

Corti, Marcelo; Minué, Gonzalo; Campitelli, Ana; Narbaitz, Marina; Gilardi, Leonardo

2015-01-01

Introduction Plasmablastic lymphoma is a rare entity that was first described in the jaws and the oral cavity of patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Plasmablastic lymphoma is considered as a diffuse, large, B-cell lymphoma with a unique phenotype and a predilection for the oral cavity. Objective The authors describe a case of an aggressive plasmablastic lymphoma of the oral cavity as the primary manifestation of AIDS. Resumed Report We report a case of plasmablastic lymphoma involving only the oral cavity as the first manifestation of AIDS. Diagnosis was confirmed by the oral lesion biopsy and the histopathologic examination that showed a dense infiltrate composed of atypical lymphocytes with numerous plasmocytes that expressed the plasma cell markers MUM-1 and CD138 and that were negative for the B-cell markers CD3, CD20, and CD45. Immunohistochemical and in situ hybridization revealed the Epstein-Barr virus genome in the atypical cells. Polymerase chain reaction was also positive for human herpesvirus-8 RNA. Conclusion The HIV serologic status should be evaluated in all patients with plasmablastic lymphoma of the oral cavity or extraoral sites. PMID:26491484

Fluorescence in situ hybridization and qPCR to detect Merkel cell polyomavirus physical status and load in Merkel cell carcinomas.

PubMed

Haugg, Anke M; Rennspiess, Dorit; zur Hausen, Axel; Speel, Ernst-Jan M; Cathomas, Gieri; Becker, Jürgen C; Schrama, David

2014-12-15

The Merkel cell polyomavirus (MCPyV) is detected in 80% of Merkel cell carcinomas (MCC). Clonal integration and tumor-specific mutations in the large T antigen are strong arguments that MCPyV is a human tumor virus. However, the relationship between viral presence and cancer induction remains discussed controversially. Since almost all studies on virus prevalence are based on PCR techniques, we performed MCPyV fluorescence in situ hybridization (FISH) on MCC to gain information about the quality of the viral presence on the single cell level. MCPyV-FISH was performed on tissue microarrays containing 62 formalin-fixed and paraffin-embedded tissue samples including all tumor grades of 42 patients. The hybridization patterns were correlated to the qPCR data determined on corresponding whole tissue sections. Indeed, MCPyV-FISH and qPCR data were highly correlated, i.e. 83% for FISH-positive and 93% for FISH-negative cores. Accordingly, the mean of the qPCR values of all MCPyV-positive cores differed significantly from the mean of the negative cores (p = 0.0076). Importantly, two hybridization patterns were definable in the MCPyV-FISH: a punctate pattern (85%) indicating viral integration, which correlated with a moderate viral abundance and a combination of the punctate with a diffuse pattern (15%), suggesting a possible coexistence of integrated and episomal virus which was associated with very high viral load and VP1 expression. Thus, MCPyV-FISH adds important information on the single cell level within the histomorphological context and could therefore be an important tool to further elucidate MCPyV related carcinogenesis. © 2014 UICC.

Definition of MYC genetic heteroclonality in diffuse large B-cell lymphoma with 8q24 rearrangement and its impact on protein expression.

PubMed

Valera, Alexandra; Epistolio, Samantha; Colomo, Lluis; Riva, Alice; Balagué, Olga; Dlouhy, Ivan; Tzankov, Alexandar; Bühler, Marco; Haralambieva, Eugenia; Campo, Elias; Soldini, Davide; Mazzucchelli, Luca; Martin, Vittoria

2016-08-01

MYC rearrangement can be detected in a subgroup of diffuse large B-cell lymphoma characterized by unfavorable prognosis. In contrast to Burkitt lymphoma, the correlation between MYC rearrangement and MYC protein expression in diffuse large B-cell lymphoma is less clear, as approximately one-third of rearranged cases show negative or low expression by immunohistochemistry. To better understand whether specific characteristics of the MYC rearrangement may influence its protein expression, we investigated 43 de novo diffuse large B-cell lymphoma positive for 8q24 rearrangement by FISH, using 14 Burkitt lymphoma for comparison. Different cell populations (clones), breakpoints (classical vs non-classical FISH patterns), partner genes (IGH vs non-IGH) and immunostaining were detected and analyzed using computerized image systems. In a subgroup of diffuse large B-cell lymphoma, we observed different clones within the same tumor distinguishing the founder clone with MYC rearrangement alone from other subclones, carrying MYC rearrangement coupled with loss/extra copies of derivatives/normal alleles. This picture, which we defined MYC genetic heteroclonality, was found in 42% of cases and correlated to negative MYC expression (P=0.026). Non-classical FISH breakpoints were detected in 16% of diffuse large B-cell lymphoma without affecting expression (P=0.040). Non-IGH gene was the preferential partner of rearrangement in those diffuse large B-cell lymphoma showing MYC heteroclonality (P=0.016) and/or non-classical FISH breakpoints (P=0.058). MYC heteroclonality was not observed in Burkitt lymphoma and all cases had positive MYC expression. Non-classical FISH MYC breakpoint and non-IGH partner were found in 29 and 20% of Burkitt lymphoma, respectively. In conclusion, MYC genetic heteroclonality is a frequent event in diffuse large B-cell lymphoma and may have a relevant role in modulating MYC expression.

Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

ClinicalTrials.gov

2018-02-08

Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndrome; Refractory Chronic Lymphocytic Leukemia; Refractory Plasma Cell Myeloma; Waldenstrom Macroglobulinemia; Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Lymphoma; Childhood Myelodysplastic Syndrome; Stage II Contiguous Adult Burkitt Lymphoma; Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Contiguous Adult Diffuse Mixed Cell Lymphoma; Stage II Contiguous Adult Diffuse Small Cleaved Cell Lymphoma; Stage II Adult Contiguous Immunoblastic Lymphoma; Stage II Contiguous Adult Lymphoblastic Lymphoma; Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Contiguous Mantle Cell Lymphoma; Stage II Non-Contiguous Adult Burkitt Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Mixed Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Small Cleaved Cell Lymphoma; Stage II Adult Non-Contiguous Immunoblastic Lymphoma; Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage II Non-Contiguous Mantle Cell Lymphoma; Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Burkitt Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Myelodysplastic Syndrome; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Immunoblastic Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Burkitt Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Childhood Burkitt Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage III Childhood Burkitt Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Childhood Burkitt Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

Lymphomas in Ile-Ife, Nigeria: Immunohistochemical Characterization and Detection of Epstein-Barr virus Encoded RNA

PubMed Central

Onwubuya, Ifeyinwa M.; Adelusola, Kayode A.; Durosinmi, Muheez A.; Ezike, Kevin N.

2015-01-01

Background The proper histopathological characterization of malignant lymphomas requires the use of immunohistochemistry along with other molecular pathology techniques. Materials and Methods Malignant lymphomas histologically diagnosed in our hospital were reclassified according to the WHO scheme using immunohistochemistry while in-situ hybridization was performed for the detection of Epstein-Barr virus encoded RNA. Results There were 83 cases of lymphoma. The male to female ratio was 1.9:1 while the overall mean age was 41.7 years. Non-Hodgkin lymphomas (NHL) constituted about 79.5% of cases. The majority of cases (98.8%) were B-cell lymphomas. Nine subtypes of lymphomas were identified with diffuse large B-cell lymphomas (56.4% of which were of the germinal centre type) constituting the largest group (47.0%). Intermediate and high grade subtypes were more common. The majority of cases (72.3%) were nodal lymphomas with cervical lymph node being the commonest site (48.2%). Only classical Hodgkin lymphoma (HL) (20.5%) was seen of which the mixed cellularity subtype was the most common. Epstein Barr virus (EBV) encoded ribonucleic acid was detected in 7 cases (8.4%) including 4 cases of HL, 2 cases of Burkitt lymphoma and the only case of plasmablastic lymphoma. About five cases were reclassified as non-lymphoid malignant lesions. Conclusion Immunohistochemistry is vital to the proper classification of lymphomas even in a resource poor environment. Although nine subtypes of lymphomas were identified, diffuse large B-cell lymphomas formed the largest single group. Epstein-Barr virus probably plays an important role in lymphomatogenesis in this environment. A larger multicentre study is required to prove this. PMID:26266128

Towards a minimal stochastic model for a large class of diffusion-reactions on biological membranes.

PubMed

Chevalier, Michael W; El-Samad, Hana

2012-08-28

Diffusion of biological molecules on 2D biological membranes can play an important role in the behavior of stochastic biochemical reaction systems. Yet, we still lack a fundamental understanding of circumstances where explicit accounting of the diffusion and spatial coordinates of molecules is necessary. In this work, we illustrate how time-dependent, non-exponential reaction probabilities naturally arise when explicitly accounting for the diffusion of molecules. We use the analytical expression of these probabilities to derive a novel algorithm which, while ignoring the exact position of the molecules, can still accurately capture diffusion effects. We investigate the regions of validity of the algorithm and show that for most parameter regimes, it constitutes an accurate framework for studying these systems. We also document scenarios where large spatial fluctuation effects mandate explicit consideration of all the molecules and their positions. Taken together, our results derive a fundamental understanding of the role of diffusion and spatial fluctuations in these systems. Simultaneously, they provide a general computational methodology for analyzing a broad class of biological networks whose behavior is influenced by diffusion on membranes.

Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

PubMed Central

dos Santos, G.C.; Parra, E.R.; Stegun, F.W.; Cirqueira, C.S.; Capelozzi, V.L.

2013-01-01

Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures. PMID:24270907

Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of radiation therapy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Shang, Yu; Li, Xingzhe; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

2016-03-01

Radiation therapy is a principal modality for head and neck cancers and its efficacy depends on tumor hemodynamics. Our laboratory developed a hybrid diffuse optical instrument allowing for simultaneous measurements of tumor blood flow and oxygenation. In this study, the clinically involved cervical lymph node was monitored by the hybrid instrument once a week over the treatment period of seven weeks. Based on treatment outcomes within one year, patients were classified into a complete response group (CR) and an incomplete response group (IR) with remote metastasis and/or local recurrence. A linear mixed models was used to compare tumor hemodynamic responses to the treatment between the two groups. Interestingly, we found that human papilloma virus (HPV-16) status largely affected tumor hemodynamic responses. For HPV-16 negative tumors, significant differences in blood flow index (BFI, p = 0.007) and reduced scattering coefficient (μs', p = 0.0005) were observed between the two groups; IR tumors exhibited higher μs' values and a continuous increase in BFI over the treatment period. For HPV-16 positive tumors, oxygenated hemoglobin concentration ([HbO2]) and blood oxygen saturation (StO2) were significant different (p = 0.003 and 0.01, respectively); IR group showed lower [HbO2] and StO2. Our results imply HPV-16 negative tumors with higher density of vasculature (μs') and higher blood flow show poor responses to radiotherapy and HPV-16 positive tumors with lower tissue oxygenation level (lower StO2 and [HbO2]) exhibit poor treatment outcomes. Our diffuse optical measurements show the great potential for early prediction of radiotherapy in head and neck cancers.

CD20-Positive nodal natural killer/T-cell lymphoma with cutaneous involvement.

PubMed

Tsai, Yi-Chiun; Chen, Chi-Kuan; Wu, Yu-Hung

2015-09-01

CD20-positive natural killer (NK)/T-cell lymphoma is extremely rare. We describe a case of a CD20-positive nodal NK/T-cell lymphoma with cutaneous involvement in a 32-year-old man. The patient presented with fever, night sweats, right inguinal lymphadenopathy and multiple violaceous to erythematous nodules and plaques on the back and bilateral legs. Immunohistochemical analysis showed diffusely and strongly positive staining for CD3, CD3 epsilon, CD43, CD56, TIA-1 and CD20 but negative staining for other B-cell markers, including CD79a and PAX-5 and T-cell markers CD5 and CD7. The tumor cell nuclei were diffusely positive for Epstein-Barr virus-encoded RNA in situ hybridization. A partial clinical response was observed after chemotherapy, indicated by the decreased size of the lymph nodes and skin lesions. It is a diagnostic challenge to deal with lymphoma cells that present with the surface proteins of both T- and B-cells. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Whole Transcriptome Sequencing Enables Discovery and Analysis of Viruses in Archived Primary Central Nervous System Lymphomas

PubMed Central

DeBoever, Christopher; Reid, Erin G.; Smith, Erin N.; Wang, Xiaoyun; Dumaop, Wilmar; Harismendy, Olivier; Carson, Dennis; Richman, Douglas; Masliah, Eliezer; Frazer, Kelly A.

2013-01-01

Primary central nervous system lymphomas (PCNSL) have a dramatically increased prevalence among persons living with AIDS and are known to be associated with human Epstein Barr virus (EBV) infection. Previous work suggests that in some cases, co-infection with other viruses may be important for PCNSL pathogenesis. Viral transcription in tumor samples can be measured using next generation transcriptome sequencing. We demonstrate the ability of transcriptome sequencing to identify viruses, characterize viral expression, and identify viral variants by sequencing four archived AIDS-related PCNSL tissue samples and analyzing raw sequencing reads. EBV was detected in all four PCNSL samples and cytomegalovirus (CMV), JC polyomavirus (JCV), and HIV were also discovered, consistent with clinical diagnoses. CMV was found to express three long non-coding RNAs recently reported as expressed during active infection. Single nucleotide variants were observed in each of the viruses observed and three indels were found in CMV. No viruses were found in several control tumor types including 32 diffuse large B-cell lymphoma samples. This study demonstrates the ability of next generation transcriptome sequencing to accurately identify viruses, including DNA viruses, in solid human cancer tissue samples. PMID:24023918

Unrecognized Emergence of Chikungunya Virus during a Zika Virus Outbreak in Salvador, Brazil

PubMed Central

Prates, Ana Paula P. B.; Paploski, Igor A. D.; Tauro, Laura B.; Silva, Monaise M. O.; Santana, Perla; Rego, Marta F. S.; Reis, Mitermayer G.; Kitron, Uriel

2017-01-01

Background Chikungunya virus (CHIKV) entered Brazil in 2014, causing a large outbreak in Feira de Santana, state of Bahia. Although cases have been recorded in Salvador, the capital of Bahia, located ~100 km of Feira de Santana, CHIKV transmission has not been perceived to occur epidemically, largely contrasting with the Zika virus (ZIKV) outbreak and ensuing complications reaching the city in 2015. Methodology/Principal Findings This study aimed to determine the intensity of CHIKV transmission in Salvador between November 2014 and April 2016. Results of all the CHIKV laboratory tests performed in the public sector were obtained and the frequency of positivity was analyzed by epidemiological week. Of the 2,736 tests analyzed, 456 (16.7%) were positive. An increasing in the positivity rate was observed, starting in January/2015, and peaking at 68% in August, shortly after the exanthematous illness outbreak attributed to ZIKV. Conclusions/Significance Public health authorities and health professionals did not immediately detect the increase in CHIKV cases, likely because all the attention was directed to the ZIKV outbreak and ensuing complications. It is important that regions in the world that harbor arbovirus vectors and did not experience intense ZIKV and CHIKV transmission be prepared for the potential co-emergence of these two viruses. PMID:28114414

Knockout of Epstein-Barr virus BPLF1 retards B-cell transformation and lymphoma formation in humanized mice.

PubMed

Whitehurst, Christopher B; Li, Guangming; Montgomery, Stephanie A; Montgomery, Nathan D; Su, Lishan; Pagano, Joseph S

2015-10-20

BPLF1 of Epstein-Barr virus (EBV) is classified as a late lytic cycle protein but is also found in the viral tegument, suggesting its potential involvement at both initial and late stages of viral infection. BPLF1 possesses both deubiquitinating and deneddylating activity located in its N-terminal domain and is involved in processes that affect viral infectivity, viral DNA replication, DNA repair, and immune evasion. A recently constructed EBV BPLF1-knockout (KO) virus was used in conjunction with a humanized mouse model that can be infected with EBV, enabling the first characterization of BPLF1 function in vivo. Results demonstrate that the BPLF1-knockout virus is approximately 90% less infectious than wild-type (WT) virus. Transformation of human B cells, a hallmark of EBV infection, was delayed and reduced with BPLF1-knockout virus. Humanized mice infected with EBV BPLF1-knockout virus showed less weight loss and survived longer than mice infected with equivalent infectious units of WT virus. Additionally, splenic tumors formed in 100% of mice infected with WT EBV but in only 25% of mice infected with BPLF1-KO virus. Morphological features of spleens containing tumors were similar to those in EBV-induced posttransplant lymphoproliferative disease (PTLD) and were almost identical to cases seen in human diffuse large B-cell lymphoma. The presence of EBV genomes was detected in all mice that developed tumors. The results implicate BPLF1 in human B-cell transformation and tumor formation in humanized mice. Epstein-Barr virus infects approximately 90% of the world's population and is the causative agent of infectious mononucleosis. EBV also causes aggressive lymphomas in individuals with acquired and innate immune disorders and is strongly associated with diffuse large B-cell lymphomas, classical Hodgkin lymphoma, Burkitt lymphoma, and nasopharyngeal carcinoma (NPC). Typically, EBV initially infects epithelial cells in the oropharynx, followed by a lifelong persistent latent infection in B-cells, which may develop into lymphomas in immunocompromised individuals. This work is the first of its kind in evaluating the effects of EBV's BPLF1 in terms of pathogenesis and lymphomagenesis in humanized mice and implicates BPLF1 in B-cell transformation and tumor development. Currently, there is no efficacious treatment for EBV, and therapeutic targeting of BPLF1 may lead to a new path to treatment for immunocompromised individuals or transplant recipients infected with EBV. Copyright © 2015 Whitehurst et al.

An unusual case of diffuse large B-cell lymphoma involving the vulva evaluated by 18F-FDG PET/CT.

PubMed

Treglia, Giorgio; Paone, Gaetano; Perriard, Ulrike; Ceriani, Luca; Giovanella, Luca

2014-10-01

We describe an unusual case of diffuse large B-cell lymphoma involving the vulva detected and staged by F-FDG PET/CT. An 83-year-old female patient with history of endometrial carcinoma underwent F-FDG PET/CT for follow-up. PET/CT detected an area of increased F-FDG uptake corresponding to a vulvar nodule; moderate and diffuse F-FDG uptake in the bone marrow was also evident. Based on these PET/CT findings, the patient underwent biopsy of the vulvar nodule. Histology demonstrated the presence of a diffuse large B-cell lymphoma of the vulva. Bone marrow biopsy was positive for lymphoid infiltration.

Hypomyelination associated with bovine viral diarrhea virus type 2 infection in a longhorn calf.

PubMed

Porter, B F; Ridpath, J F; Calise, D V; Payne, H R; Janke, J J; Baxter, D G; Edwards, J F

2010-07-01

A newborn Longhorn heifer calf presented with generalized tremors, muscle fasciculations, ataxia, and nystagmus. At necropsy, no gross central nervous system lesions were observed. Histologically, the brain and spinal cord had mild to moderate diffuse microgliosis and astrocytosis, minimal nonsuppurative encephalitis, and decreased myelin staining. Ultrastructural examination revealed thinning and absence of myelin sheaths. Various cell types were immunohistochemically positive for bovine viral diarrhea virus (BVDV). Noncytopathogenic BVDV was isolated from the brain and identified as BVDV type 2 by phylogenetic analysis. BVDV-induced hypomyelination is rare and analogous to lesions in neonates infected with border disease and classical swine fever viruses. This is the first documented case of hypomyelination in a calf specifically attributed to BVDV type 2 and the first description of the ultrastructural appearance of BVDV-induced hypomyelination.

Increasing airline travel may facilitate co-circulation of multiple dengue virus serotypes in Asia.

PubMed

Tian, Huaiyu; Sun, Zhe; Faria, Nuno Rodrigues; Yang, Jing; Cazelles, Bernard; Huang, Shanqian; Xu, Bo; Yang, Qiqi; Pybus, Oliver G; Xu, Bing

2017-08-01

The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014-2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV) serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1-3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation.

Increasing airline travel may facilitate co-circulation of multiple dengue virus serotypes in Asia

PubMed Central

Sun, Zhe; Faria, Nuno Rodrigues; Yang, Jing; Cazelles, Bernard; Huang, Shanqian; Xu, Bo; Yang, Qiqi; Pybus, Oliver G.; Xu, Bing

2017-01-01

The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014–2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV) serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1–3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation. PMID:28771468

Rumor spreading model with noise interference in complex social networks

NASA Astrophysics Data System (ADS)

Zhu, Liang; Wang, Youguo

2017-03-01

In this paper, a modified susceptible-infected-removed (SIR) model has been proposed to explore rumor diffusion on complex social networks. We take variation of connectivity into consideration and assume the variation as noise. On the basis of related literature on virus networks, the noise is described as standard Brownian motion while stochastic differential equations (SDE) have been derived to characterize dynamics of rumor diffusion both on homogeneous networks and heterogeneous networks. Then, theoretical analysis on homogeneous networks has been demonstrated to investigate the solution of SDE model and the steady state of rumor diffusion. Simulations both on Barabási-Albert (BA) network and Watts-Strogatz (WS) network display that the addition of noise accelerates rumor diffusion and expands diffusion size, meanwhile, the spreading speed on BA network is much faster than on WS network under the same noise intensity. In addition, there exists a rumor diffusion threshold in statistical average meaning on homogeneous network which is absent on heterogeneous network. Finally, we find a positive correlation between peak value of infected individuals and noise intensity while a negative correlation between rumor lifecycle and noise intensity overall.

Detection and classification of virus from electron micrograms

NASA Astrophysics Data System (ADS)

Strömberg, Jan-Olov

2010-04-01

I will present a PhD project were Diffusion Geometry is used in classification of virus particles in cell kernels from electron micrograms. I will give a very short introduction to Diffusion Geometry and discuss the main classification steps. Some preliminary result from a Master Thesis will be presented.

West Nile Virus Activity in a Winter Roost of American Crows (Corvus brachyrhynchos): Is Bird-To-Bird Transmission Important in Persistence and Amplification?

PubMed

Hinton, M G; Reisen, W K; Wheeler, S S; Townsend, A K

2015-07-01

Since its emergence in North America, West Nile virus (WNV) has had a large impact on equines, humans, and wild bird communities, yet gaps remain in our understanding of how the virus persists at temperate latitudes when winter temperatures preclude virus replication and host-seeking activity by mosquito vectors. Bird-to-bird transmission at large communal American Crow roosts could provide one mechanism for WNV persistence. Herein, we describe seasonal patterns of crow and Culex mosquito abundance, WNV infection rates, and the prevalence of WNV-positive fecal samples at a winter crow roost to test the hypothesis that bird-to-bird transmission allows WNV to persist at winter crow roosts. Samples were collected from large winter crow roosts in the Sacramento Valley of California from January 2013 until August 2014, encompassing two overwintering roost periods. West Nile virus RNA was detected in local crow carcasses in both summer [13/18 (72% WNV positive)] and winter [18/44 (41% WNV positive)] 2013-2014. Winter infections were unlikely to have arisen by recent bites from infected mosquitoes because Culex host-seeking activity was very low in winter and all Culex mosquitoes collected during winter months tested negative for WNV. Opportunities existed for fecal-oral transfer at the overwintering roost: most carcasses that tested positive for WNV had detectable viral RNA in both kidney and cloacal swabs, suggesting that infected crows were shedding virus in their feces, and >50% of crows at the roost were stained with feces by mid-winter. Moreover, 2.3% of fecal samples collected in late summer, when mosquitoes were active, tested positive for WNV RNA. Nevertheless, none of the 1,119 feces collected from three roosts over two winters contained detectable WNV RNA. This study provided evidence of WNV infection in overwintering American crows without mosquito vector activity, but did not elucidate a mechanism of WNV transmission during winter. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Systematic Epstein-Barr virus-positive T-cell lymphoproliferative disease presenting as a persistent fever and cough: a case report.

PubMed

Ameli, Fereshteh; Ghafourian, Firouzeh; Masir, Noraidah

2014-08-27

Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is an extremely rare disorder and classically arises following primary acute or chronic active Epstein-Barr virus infection. It is characterized by clonal proliferation of Epstein-Barr virus-infected T-cells with an activated cytotoxic phenotype. This disease has a rapid clinical course and is more frequent in Asia and South America, with relatively few cases being reported in Western countries. The clinical and pathological features of the disease overlap with other conditions including infectious mononucleosis, chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis and natural killer cell malignancies. We describe the rare case of systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease in a 16-year-old Malay boy. He presented with a six-month history of fever and cough, with pulmonary and mediastinal lymphadenopathy and severe pancytopenia. Medium- to large-sized, CD8+ and Epstein-Barr virus-encoded RNA-positive atypical lymphoid cells were present in the bone marrow aspirate. He subsequently developed fatal virus-associated hemophagocytic syndrome and died due to sepsis and multiorgan failure. Although systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is a disorder which is rarely encountered in clinical practice, our case report underlines the importance of a comprehensive diagnostic approach in the management of this disease. A high level of awareness of the disease throughout the diagnosis process for young patients who present with systemic illness and hemophagocytic syndrome may be of great help for the clinical diagnosis of this disease.

A reaction-diffusion within-host HIV model with cell-to-cell transmission.

PubMed

Ren, Xinzhi; Tian, Yanni; Liu, Lili; Liu, Xianning

2018-06-01

In this paper, a reaction-diffusion within-host HIV model is proposed. It incorporates cell mobility, spatial heterogeneity and cell-to-cell transmission, which depends on the diffusion ability of the infected cells. In the case of a bounded domain, the basic reproduction number [Formula: see text] is established and shown as a threshold: the virus-free steady state is globally asymptotically stable if [Formula: see text] and the virus is uniformly persistent if [Formula: see text]. The explicit formula for [Formula: see text] and the global asymptotic stability of the constant positive steady state are obtained for the case of homogeneous space. In the case of an unbounded domain and [Formula: see text], the existence of the traveling wave solutions is proved and the minimum wave speed [Formula: see text] is obtained, providing the mobility of infected cells does not exceed that of the virus. These results are obtained by using Schauder fixed point theorem, limiting argument, LaSalle's invariance principle and one-side Laplace transform. It is found that the asymptotic spreading speed may be larger than the minimum wave speed via numerical simulations. However, our simulations show that it is possible either to underestimate or overestimate the spread risk [Formula: see text] if the spatial averaged system is used rather than one that is spatially explicit. The spread risk may also be overestimated if we ignore the mobility of the cells. It turns out that the minimum wave speed could be either underestimated or overestimated as long as the mobility of infected cells is ignored.

Block effect on HCV infection by HMGB1 released from virus-infected cells: An insight from mathematical modeling

NASA Astrophysics Data System (ADS)

Wang, Wei; Ma, Wanbiao

2018-06-01

The nuclear protein high-mobility group box 1 (HMGB1) can have an active role in deoxyribonucleic acid (DNA) organization and the regulation of transcription. Based on the new findings from a recent experimental study, the blocking effect on HCV infection by HMGB1 released from virus-infected cells is investigated using a diffusive model for viral infection dynamics. In the model, the diffusion of the virus depends not only on its concentration gradient, but also on the concentration of HMGB1. The basic reproduction number, threshold dynamics, stability properties of the steady states, travelling wave solutions, and spreading speed for the proposed model are studied. We show that the HMGB1-induced blocking of HCV infection slows the spread of virus compared with random diffusion only. Numerically, it is shown that a high concentration of HMGB1 can block the spread of virus and this confirms, not only qualitatively but also quantitatively, the experimental result.

Sleep EEG of Microcephaly in Zika Outbreak.

PubMed

Kanda, Paulo Afonso Medeiros; Aguiar, Aline de Almeida Xavier; Miranda, Jose Lucivan; Falcao, Alexandre Loverde; Andrade, Claudia Suenia; Reis, Luigi Neves Dos Santos; Almeida, Ellen White R Bacelar; Bello, Yanes Brum; Monfredinho, Arthur; Kanda, Rafael Guimaraes

2018-01-01

Microcephaly (MC), previously considered rare, is now a health emergency of international concern because of the devastating Zika virus pandemic outbreak of 2015. The authors describe the electroencephalogram (EEG) findings in sleep EEG of epileptic children who were born with microcephaly in areas of Brazil with active Zika virus transmission between 2014 and 2017. The authors reviewed EEGs from 23 children. Nine were females (39.2%), and the age distribution varied from 4 to 48 months. MC was associated with mother positive serology to toxoplasmosis (toxo), rubella (rub), herpes, and dengue (1 case); toxo (1 case); chikungunya virus (CHIKV) (1 case); syphilis (1 case); and Zika virus (ZIKV) (10 cases). In addition, 1 case was associated with perinatal hypoxia and causes of 9 cases remain unknown. The main background EEG abnormality was diffuse slowing (10 cases), followed by classic (3 cases) and modified (5 cases) hypsarrhythmia. A distinct EEG pattern was seen in ZIKV (5 cases), toxo (2 cases), and undetermined cause (1 case). It was characterized by runs of frontocentrotemporal 4.5-13 Hz activity (7 cases) or diffuse and bilateral runs of 18-24 Hz (1 case). In ZIKV, this rhythmic activity was associated with hypsarrhythmia or slow background. Further studies are necessary to determine if this association is suggestive of ZIKV infection. The authors believe that EEG should be included in the investigation of all newly diagnosed congenital MC, especially those occurring in areas of autochthonous transmission of ZIKV.

Origins and evolution of viruses of eukaryotes: The ultimate modularity

PubMed Central

Koonin, Eugene V.; Dolja, Valerian V.; Krupovic, Mart

2018-01-01

Viruses and other selfish genetic elements are dominant entities in the biosphere, with respect to both physical abundance and genetic diversity. Various selfish elements parasitize on all cellular life forms. The relative abundances of different classes of viruses are dramatically different between prokaryotes and eukaryotes. In prokaryotes, the great majority of viruses possess double-stranded (ds) DNA genomes, with a substantial minority of single-stranded (ss) DNA viruses and only limited presence of RNA viruses. In contrast, in eukaryotes, RNA viruses account for the majority of the virome diversity although ssDNA and dsDNA viruses are common as well. Phylogenomic analysis yields tangible clues for the origins of major classes of eukaryotic viruses and in particular their likely roots in prokaryotes. Specifically, the ancestral genome of positive-strand RNA viruses of eukaryotes might have been assembled de novo from genes derived from prokaryotic retroelements and bacteria although a primordial origin of this class of viruses cannot be ruled out. Different groups of double-stranded RNA viruses derive either from dsRNA bacteriophages or from positive-strand RNA viruses. The eukaryotic ssDNA viruses apparently evolved via a fusion of genes from prokaryotic rolling circle-replicating plasmids and positive-strand RNA viruses. Different families of eukaryotic dsDNA viruses appear to have originated from specific groups of bacteriophages on at least two independent occasions. Polintons, the largest known eukaryotic transposons, predicted to also form virus particles, most likely, were the evolutionary intermediates between bacterial tectiviruses and several groups of eukaryotic dsDNA viruses including the proposed order “Megavirales” that unites diverse families of large and giant viruses. Strikingly, evolution of all classes of eukaryotic viruses appears to have involved fusion between structural and replicative gene modules derived from different sources along with additional acquisitions of diverse genes. PMID:25771806

Recent progress in West Nile virus diagnosis and vaccination

PubMed Central

2012-01-01

West Nile virus (WNV) is a positive-stranded RNA virus belonging to the Flaviviridae family, a large family with 3 main genera (flavivirus, hepacivirus and pestivirus). Among these viruses, there are several globally relevant human pathogens including the mosquito-borne dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV) and West Nile virus (WNV), as well as tick-borne viruses such as tick-borne encephalitis virus (TBEV). Since the mid-1990s, outbreaks of WN fever and encephalitis have occurred throughout the world and WNV is now endemic in Africa, Asia, Australia, the Middle East, Europe and the Unites States. This review describes the molecular virology, epidemiology, pathogenesis, and highlights recent progress regarding diagnosis and vaccination against WNV infections. PMID:22380523

Discovery of the first insect nidovirus, a missing evolutionary link in the emergence of the largest RNA virus genomes.

PubMed

Nga, Phan Thi; Parquet, Maria del Carmen; Lauber, Chris; Parida, Manmohan; Nabeshima, Takeshi; Yu, Fuxun; Thuy, Nguyen Thanh; Inoue, Shingo; Ito, Takashi; Okamoto, Kenta; Ichinose, Akitoyo; Snijder, Eric J; Morita, Kouichi; Gorbalenya, Alexander E

2011-09-01

Nidoviruses with large genomes (26.3-31.7 kb; 'large nidoviruses'), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7-15.7 kb; 'small nidoviruses'). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3'-5'exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60-80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3'-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3'-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2'-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that - in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses.

Detection of viruses in used ventilation filters from two large public buildings.

PubMed

Goyal, Sagar M; Anantharaman, Senthilvelan; Ramakrishnan, M A; Sajja, Suchitra; Kim, Seung Won; Stanley, Nicholas J; Farnsworth, James E; Kuehn, Thomas H; Raynor, Peter C

2011-09-01

Viral and bacterial pathogens may be present in the air after being released from infected individuals and animals. Filters are installed in the heating, ventilation, and air-conditioning (HVAC) systems of buildings to protect ventilation equipment and maintain healthy indoor air quality. These filters process enormous volumes of air. This study was undertaken to determine the utility of sampling used ventilation filters to assess the types and concentrations of virus aerosols present in buildings. The HVAC filters from 2 large public buildings in Minneapolis and Seattle were sampled to determine the presence of human respiratory viruses and viruses with bioterrorism potential. Four air-handling units were selected from each building, and a total of 64 prefilters and final filters were tested for the presence of influenza A, influenza B, respiratory syncytial, corona, parainfluenza 1-3, adeno, orthopox, entero, Ebola, Marburg, Lassa fever, Machupo, eastern equine encephalitis, western equine encephalitis, and Venezuelan equine encephalitis viruses. Representative pieces of each filter were cut and eluted with a buffer solution. Attempts were made to detect viruses by inoculation of these eluates in cell cultures (Vero, MDCK, and RK-13) and specific pathogen-free embryonated chicken eggs. Two passages of eluates in cell cultures or these eggs did not reveal the presence of any live virus. The eluates were also examined by polymerase chain reaction or reverse-transcription polymerase chain reaction to detect the presence of viral DNA or RNA, respectively. Nine of the 64 filters tested were positive for influenza A virus, 2 filters were positive for influenza B virus, and 1 filter was positive for parainfluenza virus 1. These findings indicate that existing building HVAC filters may be used as a method of detection for airborne viruses. As integrated long-term bioaerosol sampling devices, they may yield valuable information on the epidemiology and aerobiology of viruses in air that can inform the development of methods to prevent airborne transmission of viruses and possible deterrents against the spread of bioterrorism agents. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Visualizing interactions between Sindbis virus and cells by single particle tracking

NASA Astrophysics Data System (ADS)

Williard, Mary

2005-03-01

Sindbis virus infects both mammalian and insect cells. Though not pathogenic in humans, Sindbis is a model for many mosquito- borne viruses that cause human disease, such as West Nile virus. We have used real-time single particle fluorescence microscopy to observe individual Sindbis virus particles as they infect living cells. Fluorescent labels were incorporated into both the viral coat proteins and the lipid envelope of the virus. Kinetics characteristic of free diffusion in solution, slower diffusion inside cells, attachment to spots on the cell surface, and motor protein transport inside cells have been observed. Dequenching of the membrane label is used to report membrane fusion events during the infection process. Tracking individual viral particles allows multiple pathways to be determined without the requirement of synchronicity.

Infection of Polarized Cultures of Human Intestinal Epithelial Cells with Hepatitis A Virus: Vectorial Release of Progeny Virions through Apical Cellular Membranes

PubMed Central

Blank, Christian A.; Anderson, David A.; Beard, Michael; Lemon, Stanley M.

2000-01-01

Although hepatitis A virus (HAV) is typically transmitted by the fecal-oral route, little is known of its interactions with cells of the gastrointestinal tract. We studied the replication of HAV in polarized cultures of Caco-2 cells, a human cell line which retains many differentiated functions of small intestinal epithelial cells. Virus uptake was 30- to 40-fold more efficient when the inoculum was placed on the apical rather than the basolateral surface of these cells, suggesting a greater abundance of the cellular receptor for HAV on the apical surface. Infection proceeded without cytopathic effect and did not influence transepithelial resistance or the diffusion of inulin across cell monolayers. Nonetheless, there was extensive release of progeny virus, which occurred almost exclusively into apical supernatant fluids (36.4% ± 12.5% of the total virus yield compared with 0.23% ± 0.13% release into basolateral fluids). Brefeldin A caused a profound inhibition of HAV replication, but also selectively reduced apical release of virus. These results indicate that polarized human epithelial cell cultures undergo vectorial infection with HAV and that virus release is largely restricted to the apical membrane. Virus release occurs in the absence of cytopathic effect and may involve cellular vesicular transport mechanisms. PMID:10864660

An Adult Case of Chronic Active Epstein-Barr Virus Infection with Interstitial Pneumonitis

PubMed Central

Joo, Eun-Jeong; Ha, Young Eun; Jung, Dong Sik; Cheong, Hae Suk; Wi, Yu Mi; Song, Jae-Hoon

2011-01-01

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment. PMID:22205850

An adult case of chronic active Epstein-Barr virus infection with interstitial pneumonitis.

PubMed

Joo, Eun-Jeong; Ha, Young Eun; Jung, Dong Sik; Cheong, Hae Suk; Wi, Yu Mi; Song, Jae-Hoon; Peck, Kyong Ran

2011-12-01

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment.

New emergence pattern with variant porcine epidemic diarrhea viruses, South Korea, 2012-2015.

PubMed

Chung, Hee-Chun; Lee, Jee-Hoon; Nguyen, Van Giap; Huynh, Thi My Le; Lee, Ga-Eun; Moon, Hyoung-Joon; Park, Seong-Jun; Kim, Hye-Kwon; Park, Bong Kyun

2016-12-02

Since outbreaks of porcine epidemic diarrhea virus (PEDV) in the United States in 2013, explosive outbreaks of PED in South Korea have infected all age groups of pigs in 2014-2015year. This study analyzed a large collection of the Spike protein coding gene to infer the spatial-temporal diffusion history of PEDV. The studying results suggested that PEDVs in Korea belonged to different genogroups. While classical G1 was continuingly circulating between provinces of Korea, the pandemic G2a were recently introduced from China and USA. By the application of Bayesian phylogeographical analysis, this study demonstrated the spatial-temporal transmission of PEDVs within Korea. Of the recent emerged G2a viruses, J3142 strains showed potential recombination breakpoint (376-2,143nt) of S1 gene between KNU1303_Korea strain_G2a (KJ451046) and 45RWVCF0712_Thailand strain_G2b (KF724935). The pandemic G2a virus was partial neutralized by the antibodies invoked by the G1- based PED vaccine virus. Copyright © 2016. Published by Elsevier B.V.

A cross-diffusion system derived from a Fokker-Planck equation with partial averaging

NASA Astrophysics Data System (ADS)

Jüngel, Ansgar; Zamponi, Nicola

2017-02-01

A cross-diffusion system for two components with a Laplacian structure is analyzed on the multi-dimensional torus. This system, which was recently suggested by P.-L. Lions, is formally derived from a Fokker-Planck equation for the probability density associated with a multi-dimensional Itō process, assuming that the diffusion coefficients depend on partial averages of the probability density with exponential weights. A main feature is that the diffusion matrix of the limiting cross-diffusion system is generally neither symmetric nor positive definite, but its structure allows for the use of entropy methods. The global-in-time existence of positive weak solutions is proved and, under a simplifying assumption, the large-time asymptotics is investigated.

Interplay between translational diffusion and large-amplitude angular jumps of water molecules

NASA Astrophysics Data System (ADS)

Liu, Chao; Zhang, Yangyang; Zhang, Jian; Wang, Jun; Li, Wenfei; Wang, Wei

2018-05-01

Understanding the microscopic mechanism of water molecular translational diffusion is a challenging topic in both physics and chemistry. Here, we report an investigation on the interplay between the translational diffusion and the large-amplitude angular jumps of water molecules in bulk water using molecular dynamics simulations. We found that large-amplitude angular jumps are tightly coupled to the translational diffusions. Particularly, we revealed that concurrent rotational jumps of spatially neighboring water molecules induce inter-basin translational jumps, which contributes to the fast component of the water translational diffusion. Consequently, the translational diffusion shows positional heterogeneity; i.e., the neighbors of the water molecules with inter-basin translational jumps have larger probability to diffuse by inter-basin translational jumps. Our control simulations showed that a model water molecule with moderate hydrogen bond strength can diffuse much faster than a simple Lennard-Jones particle in bulk water due to the capability of disturbing the hydrogen bond network of the surrounding water molecules. Our results added to the understanding of the microscopic picture of the water translational diffusion and demonstrated the unique features of water diffusion arising from their hydrogen bond network structure compared with those of the simple liquids.

Pinpointing retrovirus entry sites in cells expressing alternatively spliced receptor isoforms by single virus imaging.

PubMed

Padilla-Parra, Sergi; Marin, Mariana; Kondo, Naoyuki; Melikyan, Gregory B

2014-06-16

The majority of viruses enter host cells via endocytosis. Current knowledge of viral entry pathways is largely based upon infectivity measurements following genetic and/or pharmacological interventions that disrupt vesicular trafficking and maturation. Imaging of single virus entry in living cells provides a powerful means to delineate viral trafficking pathways and entry sites under physiological conditions. Here, we visualized single avian retrovirus co-trafficking with markers for early (Rab5) and late (Rab7) endosomes, acidification of endosomal lumen and the resulting viral fusion measured by the viral content release into the cytoplasm. Virus-carrying vesicles either merged with the existing Rab5-positive early endosomes or slowly accumulated Rab5. The Rab5 recruitment to virus-carrying endosomes correlated with acidification of their lumen. Viral fusion occurred either in early (Rab5-positive) or intermediate (Rab5- and Rab7-positive) compartments. Interestingly, different isoforms of the cognate receptor directed virus entry from distinct endosomes. In cells expressing the transmembrane receptor, viruses preferentially entered and fused with slowly maturing early endosomes prior to accumulation of Rab7. By comparison, in cells expressing the GPI-anchored receptor, viruses entered both slowly and quickly maturing endosomes and fused with early (Rab5-positive) and intermediate (Rab5- and Rab7-positive) compartments. Since the rate of low pH-triggered fusion was independent of the receptor isoform, we concluded that the sites of virus entry are determined by the kinetic competition between endosome maturation and viral fusion. Our findings demonstrate the ability of this retrovirus to enter cells via alternative endocytic pathways and establish infection by releasing its content from distinct endosomal compartments.

A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus.

PubMed

Cheng, Han; Koning, Katie; O'Hearn, Aileen; Wang, Minxiu; Rumschlag-Booms, Emily; Varhegyi, Elizabeth; Rong, Lijun

2015-11-24

Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.

A Case of Primary Central Nervous System Lymphoma Located at Brain Stem in a Child.

PubMed

Kim, Jinho; Kim, Young Zoon

2016-10-01

Primary central nervous system lymphoma (PCNSL) is an extranodal Non-Hodgkin's lymphoma that is confined to the brain, eyes, and/or leptomeninges without evidence of a systemic primary tumor. Although the tumor can affect all age groups, it is rare in childhood; thus, its incidence and prognosis in children have not been well defined and the best treatment strategy remains unclear. A nine-year old presented at our department with complaints of diplopia, dizziness, dysarthria, and right side hemiparesis. Magnetic resonance image suggested a diffuse brain stem glioma with infiltration into the right cerebellar peduncle. The patient was surgically treated by craniotomy and frameless stereotactic-guided biopsy, and unexpectedly, the histopathology of the mass was consistent with diffuse large B cell lymphoma, and immunohistochemical staining revealed positivity for CD20 and CD79a. Accordingly, we performed a staging work-up for systemic lymphoma, but no evidence of lymphoma elsewhere in the body was obtained. In addition, she had a negative serologic finding for human immunodeficient virus, which confirmed the histopathological diagnosis of PCNSL. She was treated by radiosurgery at 12 Gy and subsequent adjuvant combination chemotherapy based on high dose methotrexate. Unfortunately, 10 months after the tissue-based diagnosis, she succumbed due to an acute hydrocephalic crisis.

Genomic analysis of influenza A virus from captive wild boars in Brazil reveals a human-like H1N2 influenza virus.

PubMed

Biondo, Natalha; Schaefer, Rejane; Gava, Danielle; Cantão, Mauricio E; Silveira, Simone; Mores, Marcos A Z; Ciacci-Zanella, Janice R; Barcellos, David E S N

2014-01-10

Influenza is a viral disease that affects human and several animal species. In Brazil, H1N1, H3N2 and 2009 pandemic H1N1 A(H1N1)pdm09 influenza A viruses (IAV) circulate in domestic swine herds. Wild boars are also susceptible to IAV infection but in Brazil until this moment there are no reports of IAV infection in wild boars or in captive wild boars populations. Herein the occurrence of IAV in captive wild boars with the presence of lung consolidation lesions during slaughter was investigated. Lung samples were screened by RT-PCR for IAV detection. IAV positive samples were further analyzed by quantitative real-time PCR (qRRT-PCR), virus isolation, genomic sequencing, histopathology and immunohistochemistry (IHC). Eleven out of 60 lungs (18.3%) were positive for IAV by RT-PCR and seven out of the eleven were also positive for A(H1N1)pdm09 by qRRT-PCR. Chronic diffuse bronchopneumonia was observed in all samples and IHC analysis was negative for influenza A antigen. Full genes segments of H1N2 IAV were sequenced using Illumina's genome analyzer platform (MiSeq). The genomic analysis revealed that the HA and NA genes clustered with IAVs of the human lineage and the six internal genes were derived from the H1N1pdm09 IAV. This is the first report of a reassortant human-like H1N2 influenza virus infection in captive wild boars in Brazil and indicates the need to monitor IAV evolution in Suidae populations. Copyright © 2013 Elsevier B.V. All rights reserved.

RNA interference inhibits herpes simplex virus type 1 isolated from saliva samples and mucocutaneous lesions.

PubMed

Silva, Amanda Perse da; Lopes, Juliana Freitas; Paula, Vanessa Salete de

2014-01-01

The aim of this study was to evaluate the use of RNA interference to inhibit herpes simplex virus type-1 replication in vitro. For herpes simplex virus type-1 gene silencing, three different small interfering RNAs (siRNAs) targeting the herpes simplex virus type-1 UL39 gene (sequence si-UL 39-1, si-UL 39-2, and si-UL 39-3) were used, which encode the large subunit of ribonucleotide reductase, an essential enzyme for DNA synthesis. Herpes simplex virus type-1 was isolated from saliva samples and mucocutaneous lesions from infected patients. All mucocutaneous lesions' samples were positive for herpes simplex virus type-1 by real-time PCR and by virus isolation; all herpes simplex virus type-1 from saliva samples were positive by real-time PCR and 50% were positive by virus isolation. The levels of herpes simplex virus type-1 DNA remaining after siRNA treatment were assessed by real-time PCR, whose results demonstrated that the effect of siRNAs on gene expression depends on siRNA concentration. The three siRNA sequences used were able to inhibit viral replication, assessed by real-time PCR and plaque assays and among them, the sequence si-UL 39-1 was the most effective. This sequence inhibited 99% of herpes simplex virus type-1 replication. The results demonstrate that silencing herpes simplex virus type-1 UL39 expression by siRNAs effectively inhibits herpes simplex virus type-1 replication, suggesting that siRNA based antiviral strategy may be a potential therapeutic alternative. Copyright © 2014. Published by Elsevier Editora Ltda.

In silico mutation analysis of non-structural protein-5 (NS5) dengue virus

NASA Astrophysics Data System (ADS)

Puspitasari, R. D.; Tambunan, U. S. F.

2017-04-01

Dengue fever is a world disease. It is endemic in more than 100 countries. Information about the effect of mutations in the virus is important in drug design and development. In this research, we studied the effect of mutation on NS5 dengue virus. NS5 is the large protein containing 67% amino acid similarity in DENV 1-4 and has multifunctional enzymatic activities. Dengue virus is an RNA virus that has very high mutation frequency with an average of 100 times higher than DNA mutations, and the accumulation of mutations will be possible to generate the new serotype. In this study, we report that mutation occurs in NS5 of DENV serotype 3, glutamine mutates into methionine at position 10 and threonine mutates into isoleucine at position 55. These residues are part of the domain named S-Adenosyl-L-Methionine-Dependent Methyltransferase (IPR029063).

New MYC IHC Classifier Integrating Quantitative Architecture Parameters to Predict MYC Gene Translocation in Diffuse Large B-Cell Lymphoma

PubMed Central

Dong, Wei-Feng; Canil, Sarah; Lai, Raymond; Morel, Didier; Swanson, Paul E.; Izevbaye, Iyare

2018-01-01

A new automated MYC IHC classifier based on bivariate logistic regression is presented. The predictor relies on image analysis developed with the open-source ImageJ platform. From a histologic section immunostained for MYC protein, 2 dimensionless quantitative variables are extracted: (a) relative distance between nuclei positive for MYC IHC based on euclidean minimum spanning tree graph and (b) coefficient of variation of the MYC IHC stain intensity among MYC IHC-positive nuclei. Distance between positive nuclei is suggested to inversely correlate MYC gene rearrangement status, whereas coefficient of variation is suggested to inversely correlate physiological regulation of MYC protein expression. The bivariate classifier was compared with 2 other MYC IHC classifiers (based on percentage of MYC IHC positive nuclei), all tested on 113 lymphomas including mostly diffuse large B-cell lymphomas with known MYC fluorescent in situ hybridization (FISH) status. The bivariate classifier strongly outperformed the “percentage of MYC IHC-positive nuclei” methods to predict MYC+ FISH status with 100% sensitivity (95% confidence interval, 94-100) associated with 80% specificity. The test is rapidly performed and might at a minimum provide primary IHC screening for MYC gene rearrangement status in diffuse large B-cell lymphomas. Furthermore, as this bivariate classifier actually predicts “permanent overexpressed MYC protein status,” it might identify nontranslocation-related chromosomal anomalies missed by FISH. PMID:27093450

De novo CD5-positive primary cardiac diffuse large B-cell lymphoma diagnosed by pleural fluid cytology.

PubMed

Cioc, Adina M; Jessurun, José; Vercellotti, Gregory M; Pambuccian, Stefan E

2014-03-01

Primary cardiac lymphomas are exceedingly rare. The presence and extent of the intracardiac mass is determined by echocardiography, computed tomography (CT), or magnetic resonance imaging (MRI); however, the diagnosis is established by endomyocardial biopsy or by pericardial or pleural effusion cytology. We describe the pleural effusion cytologic features of a primary cardiac lymphoma in a 55-year-old woman who presented with progressive shortness of breath, fatigue, mild dizziness, dull chest ache, and lower extremity edema. Transthoracic echocardiography, CT, and MRI showed a large mass centered in the right atrium and extending into the right ventricle, associated with pericardial effusion and bilateral pleural effusions. Cytologic examination of the pleural fluid showed very large pleomorphic malignant cell, some of which were binucleated and multinucleated and had anaplastic features. Flow cytometry showed a kappa monotypic population of large cells coexpressing CD5, CD19, and CD20; and immunoperoxidase stains performed on the cell block sections showed that the large neoplastic cells were positive for CD20, PAX5, CD5, and MUM1 and showed a very high proliferation rate (over 90%) by Ki67 staining. The cytologic, flow cytometry, and immunohistochemistry findings established the diagnosis of de novo CD5-positive primary cardiac diffuse large B-cell lymphoma (DLBCL), anaplastic variant, which was confirmed by the subsequent endomyocardial biopsy. This is, to the best of our knowledge, the first report of de novo CD5-positive primary cardiac diffuse large B-cell lymphoma, and the first report of the anaplastic variant of DLBCL diagnosed by effusion cytology. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Integrating Models of Diffusion and Behavior to Predict Innovation Adoption, Maintenance, and Social Diffusion.

PubMed

Smith, Rachel A; Kim, Youllee; Zhu, Xun; Doudou, Dimi Théodore; Sternberg, Eleanore D; Thomas, Matthew B

2018-01-01

This study documents an investigation into the adoption and diffusion of eave tubes, a novel mosquito vector control, during a large-scale scientific field trial in West Africa. The diffusion of innovations (DOI) and the integrated model of behavior (IMB) were integrated (i.e., innovation attributes with attitudes and social pressures with norms) to predict participants' (N = 329) diffusion intentions. The findings showed that positive attitudes about the innovation's attributes were a consistent positive predictor of diffusion intentions: adopting it, maintaining it, and talking with others about it. As expected by the DOI and the IMB, the social pressure created by a descriptive norm positively predicted intentions to adopt and maintain the innovation. Drawing upon sharing research, we argued that the descriptive norm may dampen future talk about the innovation, because it may no longer be seen as a novel, useful topic to discuss. As predicted, the results showed that as the descriptive norm increased, the intention to talk about the innovation decreased. These results provide broad support for integrating the DOI and the IMB to predict diffusion and for efforts to draw on other research to understand motivations for social diffusion.

Sirolimus, Cyclosporine, and Mycophenolate Mofetil in Preventing Graft-versus-Host Disease in Treating Patients With Blood Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant

ClinicalTrials.gov

2017-10-30

Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloid Leukemia; Adult Diffuse Large B-Cell Lymphoma; Adult Myelodysplastic Syndrome; Adult Non-Hodgkin Lymphoma; Aggressive Non-Hodgkin Lymphoma; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia; Childhood Diffuse Large B-Cell Lymphoma; Childhood Myelodysplastic Syndrome; Childhood Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Chronic Lymphocytic Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic and Lymphoid Cell Neoplasm; Mantle Cell Lymphoma; Plasma Cell Myeloma; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma

Bluetongue virus spread in Europe is a consequence of climatic, landscape and vertebrate host factors as revealed by phylogeographic inference

PubMed Central

Palmarini, Massimo; Mertens, Peter

2017-01-01

Spatio-temporal patterns of the spread of infectious diseases are commonly driven by environmental and ecological factors. This is particularly true for vector-borne diseases because vector populations can be strongly affected by host distribution as well as by climatic and landscape variables. Here, we aim to identify environmental drivers for bluetongue virus (BTV), the causative agent of a major vector-borne disease of ruminants that has emerged multiple times in Europe in recent decades. In order to determine the importance of climatic, landscape and host-related factors affecting BTV diffusion across Europe, we fitted different phylogeographic models to a dataset of 113 time-stamped and geo-referenced BTV genomes, representing multiple strains and serotypes. Diffusion models using continuous space revealed that terrestrial habitat below 300 m altitude, wind direction and higher livestock densities were associated with faster BTV movement. Results of discrete phylogeographic analysis involving generalized linear models broadly supported these findings, but varied considerably with the level of spatial partitioning. Contrary to common perception, we found no evidence for average temperature having a positive effect on BTV diffusion, though both methodological and biological reasons could be responsible for this result. Our study provides important insights into the drivers of BTV transmission at the landscape scale that could inform predictive models of viral spread and have implications for designing control strategies. PMID:29021180

Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes

PubMed Central

Parida, Manmohan; Nabeshima, Takeshi; Yu, Fuxun; Thuy, Nguyen Thanh; Inoue, Shingo; Ito, Takashi; Okamoto, Kenta; Ichinose, Akitoyo; Snijder, Eric J.; Morita, Kouichi; Gorbalenya, Alexander E.

2011-01-01

Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses. PMID:21931546

Biopsy-proven case of Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system.

PubMed

Kano, Kohei; Katayama, Takayuki; Takeguchi, Shiori; Asanome, Asuka; Takahashi, Kae; Saito, Tsukasa; Sawada, Jun; Saito, Masato; Anei, Ryogo; Kamada, Kyousuke; Miyokawa, Naoyuki; Nishihara, Hiroshi; Hasebe, Naoyuki

2017-06-01

A 75-year-old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7-year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2-weighted MRI showed diffuse high-intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein-Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV-encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system. High-dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy-proven EBV-positive/HIV-negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV-associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis. © 2016 Japanese Society of Neuropathology.

Continental synchronicity of human influenza virus epidemics despite climatic variation.

PubMed

Geoghegan, Jemma L; Saavedra, Aldo F; Duchêne, Sebastián; Sullivan, Sheena; Barr, Ian; Holmes, Edward C

2018-01-01

The factors that determine the pattern and rate of spread of influenza virus at a continental-scale are uncertain. Although recent work suggests that influenza epidemics in the United States exhibit a strong geographical correlation, the spatiotemporal dynamics of influenza in Australia, a country and continent of approximately similar size and climate complexity but with a far smaller population, are not known. Using a unique combination of large-scale laboratory-confirmed influenza surveillance comprising >450,000 entries and genomic sequence data we determined the local-level spatial diffusion of this important human pathogen nationwide in Australia. We used laboratory-confirmed influenza data to characterize the spread of influenza virus across Australia during 2007-2016. The onset of established epidemics varied across seasons, with highly synchronized epidemics coinciding with the emergence of antigenically distinct viruses, particularly during the 2009 A/H1N1 pandemic. The onset of epidemics was largely synchronized between the most populous cities, even those separated by distances of >3000 km and those that experience vastly diverse climates. In addition, by analyzing global phylogeographic patterns we show that the synchronized dissemination of influenza across Australian cities involved multiple introductions from the global influenza population, coupled with strong domestic connectivity, rather than through the distinct radial patterns of geographic dispersal that are driven by work-flow transmission as observed in the United States. In addition, by comparing the spatial structure of influenza A and B, we found that these viruses tended to occupy different geographic regions, and peak in different seasons, perhaps indicative of moderate cross-protective immunity or viral interference effects. The highly synchronized outbreaks of influenza virus at a continental-scale revealed here highlight the importance of coordinated public health responses in the event of the emergence of a novel, human-to-human transmissible, virus.

Mechanism of Enhancement of Virus Plaques by Cationic Polymers

PubMed Central

Wallis, Craig; Melnick, Joseph L.

1968-01-01

It has been assumed that plaque enhancement by cationic polymers is due to their binding of sulfated polysaccharides in agar. However, viruses that are enhanced by cationic polymers, diethylaminoethyl-dextran, and protamine were found not to be inhibited by polyanions in agar under the usual overlay conditions. In the case of adenovirus, enhancement by protamine seems to be due to the protamine serving as a source of arginine; enzymes released from the cultured cells digest the protamine and provide a reservoir of arginine for the cells. Other viruses (herpes and echovirus types 3, 4, 5, and 6) known to be susceptible to agar inhibitors were found to be enhanced by cationic polymers even under starch gel and methylcellulose overlays, which are free of polyanions. Since cationic polymers enhance the diffusion of virus through agar or starch gel, plaque enhancement seems to be the result of the gel becoming positively charged so that viruses can move effectively through them. The observation that starch gel and methylcellulose enhance plaque formation with viruses known to be inhibited under agar was also reinvestigated. When the consistency of the agar gel was reduced to the same viscosity of starch gel and methylcellulose overlays, the same plaque counts and sizes were observed under all three overlays. PMID:4986901

SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells

PubMed Central

Mossel, Eric C.; Wang, Jieru; Jeffers, Scott; Edeen, Karen E.; Wang, Shuanglin; Cosgrove, Gregory P.; Funk, C. Joel; Manzer, Rizwan; Miura, Tanya A.; Pearson, Leonard D.; Holmes, Kathryn V.; Mason, Robert J.

2008-01-01

Severe acute respiratory syndrome (SARS) is a disease characterized by diffuse alveolar damage. We isolated alveolar type II cells and maintained them in a highly differentiated state. Type II cell cultures supported SARS-CoV replication as evidenced by RT-PCR detection of viral subgenomic RNA and an increase in virus titer. Virus titers were maximal by 24 hours and peaked at approximately 105 pfu/mL. Two cell types within the cultures were infected. One cell type was type II cells, which were positive for SP-A, SP-C, cytokeratin, a type II cell-specific monoclonal antibody, and Ep-CAM. The other cell type was composed of spindle-shaped cells that were positive for vimentin and collagen III and likely fibroblasts. Viral replication was not detected in type I-like cells or macrophages. Hence, differentiated adult human alveolar type II cells were infectible but alveolar type I-like cells and alveolar macrophages did not support productive infection. PMID:18022664

Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2017-10-24

CD19-Positive Neoplastic Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Acute Lymphoblastic Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

Studies on the serological relationships between avian pox, sheep pox, goat pox and vaccinia viruses

PubMed Central

Uppal, P. K.; Nilakantan, P. R.

1970-01-01

By using neutralization, complement fixation and immunogel-diffusion tests, it has been demonstrated that cross-reactions occur between various avian pox viruses and between sheep pox and goat pox viruses. No such reactions were demonstrated between avian pox viruses and vaccinia virus or between avian pox and sheep pox and goat pox viruses. Furthermore, no serological relationship was demonstrable between vaccinia virus and sheep pox and goat pox viruses. PMID:4989854

Multiple Genetic Pathways Involving Amino Acid Position 143 of HIV-1 Integrase Are Preferentially Associated with Specific Secondary Amino Acid Substitutions and Confer Resistance to Raltegravir and Cross-Resistance to Elvitegravir

PubMed Central

Frantzell, Arne; Fransen, Signe; Petropoulos, Christos J.

2013-01-01

Y143C,R substitutions in HIV-1 integrase define one of three primary raltegravir (RAL) resistance pathways. Here we describe clinical isolates with alternative substitutions at position 143 (Y143A, Y143G, Y143H, and Y143S [Y143A,G,H,S]) that emerge less frequently, and we compare the genotypic and phenotypic profiles of these viruses to Y143C,R viruses to reconcile the preferential selection of Y143C,R variants during RAL treatment. Integrase amino acid sequences and RAL susceptibility were characterized in 117 patient isolates submitted for drug resistance testing and contained Y143 amino acid changes. The influence of specific Y143 substitutions on RAL susceptibility and their preferential association with particular secondary substitutions were further defined by evaluating the composition of patient virus populations along with a large panel of site-directed mutants. Our observations demonstrate that the RAL resistance profiles of Y143A,G,H,S viruses and their association with specific secondary substitutions are similar to the well-established Y143C profile but distinct from the Y143R profile. Y143R viruses differ from Y143A,C,G,H,S viruses in that Y143R confers a greater reduction in RAL susceptibility as a single substitution, consistent with a lower resistance barrier. Among Y143A,C,G,H,S viruses, the higher prevalence of Y143C viruses is the result of a lower genetic barrier than that of the Y143A,G,S viruses and a lower resistance barrier than that of the Y143H viruses. In addition, Y143A,C,G,H,S viruses require multiple secondary substitutions to develop large reductions in RAL susceptibility. Patient-derived viruses containing Y143 substitutions exhibit cross-resistance to elvitegravir. PMID:23733474

Epidemiological Survey of Human Metapneumovirus Infection in a Large Pediatric Tertiary Care Center

PubMed Central

Chano, Frédéric; Rousseau, Céline; Laferrière, Céline; Couillard, Michel; Charest, Hugues

2005-01-01

The human metapneumovirus (hMPV) was recently identified and linked to acute respiratory tract infections (ARTI). To assess the clinical importance of this virus in infants and children, we developed a rapid and efficient reverse transcription-PCR-based screening method for a large volume of samples and tested retrospectively a collection of 1,132 respiratory specimens submitted over a full year period to the virology laboratory of a large tertiary care pediatric center in Montreal, Canada. A total of 41 samples from 37 patients were positive by this method. During the winter months of 2001, up to 8% of specimens submitted for respiratory virus testing were hMPV positive. Sequencing data of the hMPV M gene revealed that two genogroups of the virus, each of which can be divided into two subgroups, cocirculated during this time period. A case-controlled study was conducted to compare the symptoms associated with hMPV infection with those involving other etiologic agents causing ARTI. Symptoms most frequently observed in hMPV-positive patients were cough, wheezing, and dyspnea, although the symptomatology could differ substantially from patient to patient. No distinct symptom profile could be associated with hMPV. Three nosocomial cases of hMPV infection were identified. Together, our data suggest that hMPV is a significant cause of symptomatic respiratory tract infections in infants and children. The incidence of the disease and the morbidity associated with the infection justify adding hMPV to the list of common respiratory viruses routinely screened for by clinical laboratories. PMID:16272480

Detection of 12 respiratory viruses by duplex real time PCR assays in respiratory samples.

PubMed

Arvia, Rosaria; Corcioli, Fabiana; Ciccone, Nunziata; Della Malva, Nunzia; Azzi, Alberta

2015-12-01

Different viruses can be responsible for similar clinical manifestations of respiratory infections. Thus, the etiological diagnosis of respiratory viral diseases requires the detection of a large number of viruses. In this study, 6 duplex real-time PCR assays, using EvaGreen intercalating dye, were developed to detect 12 major viruses responsible for respiratory diseases: influenza A and B viruses, enteroviruses (including enterovirus spp, and rhinovirus spp), respiratory syncytial virus, human metapneumovirus, coronaviruses group I (of which CoV 229E and CoV NL63 are part) and II (including CoV OC43 and CoV HKU1), parainfluenza viruses type 1, 2, 3 and 4, human adenoviruses and human bocaviruses. The 2 target viruses of each duplex reaction were distinguishable by the melting temperatures of their amplicons. The 6 duplex real time PCR assays were applied for diagnostic purpose on 202 respiratory samples from 157 patients. One hundred fifty-seven samples were throat swabs and 45 were bronchoalveolar lavages. The results of the duplex PCR assays were confirmed by comparison with a commercial, validated, assay; in addition, the positive results were confirmed by sequencing. The analytical sensitivity of the duplex PCR assays varied from 10(3) copies/ml to 10(4) copies/ml. For parainfluenza virus 2 only it was 10(5) copies/ml. Seventy clinical samples (35%) from 55 patients (30 children and 25 adults) were positive for 1 or more viruses. In adult patients, influenza A virus was the most frequently detected respiratory virus followed by rhinoviruses. In contrast, respiratory syncytial virus was the most common virus in children, followed by enteroviruses, influenza A virus and coronavirus NL63. The small number of samples/patients does not allow us to draw any epidemiological conclusion. Altogether, the results of this study indicate that the 6 duplex PCR assays described in this study are sensitive, specific and cost-effective. Thus, this assay could be particularly useful to identify the main respiratory viruses directly from clinical samples, after nucleic acid extraction, and, also, to screen a large number of patients for epidemiological studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Viruses Infecting Reptiles

PubMed Central

Marschang, Rachel E.

2011-01-01

A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch’s postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions. PMID:22163336

Viruses infecting reptiles.

PubMed

Marschang, Rachel E

2011-11-01

A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch's postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.

Spatial spreading model and dynamics of West Nile virus in birds and mosquitoes with free boundary.

PubMed

Lin, Zhigui; Zhu, Huaiping

2017-12-01

In this paper, a reaction-diffusion system is proposed to model the spatial spreading of West Nile virus in vector mosquitoes and host birds in North America. Transmission dynamics are based on a simplified model involving mosquitoes and birds, and the free boundary is introduced to model and explore the expanding front of the infected region. The spatial-temporal risk index [Formula: see text], which involves regional characteristic and time, is defined for the simplified reaction-diffusion model with the free boundary to compare with other related threshold values, including the usual basic reproduction number [Formula: see text]. Sufficient conditions for the virus to vanish or to spread are given. Our results suggest that the virus will be in a scenario of vanishing if [Formula: see text], and will spread to the whole region if [Formula: see text] for some [Formula: see text], while if [Formula: see text], the spreading or vanishing of the virus depends on the initial number of infected individuals, the area of the infected region, the diffusion rate and other factors. Moreover, some remarks on the basic reproduction numbers and the spreading speeds are presented and compared.

Infant outcomes among women with Zika virus infection during pregnancy: results of a large prenatal Zika screening program.

PubMed

Adhikari, Emily H; Nelson, David B; Johnson, Kathryn A; Jacobs, Sara; Rogers, Vanessa L; Roberts, Scott W; Sexton, Taylor; McIntire, Donald D; Casey, Brian M

2017-03-01

Zika virus infection during pregnancy is a known cause of congenital microcephaly and other neurologic morbidities. We present the results of a large-scale prenatal screening program in place at a single-center health care system since March 14, 2016. Our aims were to report the baseline prevalence of travel-associated Zika infection in our pregnant population, determine travel characteristics of women with evidence of Zika infection, and evaluate maternal and neonatal outcomes compared to women without evidence of Zika infection. This is a prospective, observational study of prenatal Zika virus screening in our health care system. We screened all pregnant women for recent travel to a Zika-affected area, and the serum was tested for those considered at risk for infection. We compared maternal demographic and travel characteristics and perinatal outcomes among women with positive and negative Zika virus tests during pregnancy. Comprehensive neurologic evaluation was performed on all infants delivered of women with evidence of possible Zika virus infection during pregnancy. Head circumference percentiles by gestational age were compared for infants delivered of women with positive and negative Zika virus test results. From March 14 through Oct. 1, 2016, a total of 14,161 pregnant women were screened for travel to a Zika-affected country. A total of 610 (4.3%) women reported travel, and test results were available in 547. Of these, evidence of possible Zika virus infection was found in 29 (5.3%). In our population, the prevalence of asymptomatic or symptomatic Zika virus infection among pregnant women was 2/1000. Women with evidence of Zika virus infection were more likely to have traveled from Central or South America (97% vs 12%, P < .001). There were 391 deliveries available for analysis. There was no significant difference in obstetric or neonatal morbidities among women with or without evidence of possible Zika virus infection. Additionally, there was no difference in mean head circumference of infants born to women with positive vs negative Zika virus testing. No microcephalic infants born to women with Zika infection were identified, although 1 infant with hydranencephaly was born to a woman with unconfirmed possible Zika disease. Long-term outcomes for infants exposed to maternal Zika infection during pregnancy are yet unknown. Based on a large-scale prenatal Zika screening program in an area with a predominantly Hispanic population, we identified that 4% were at risk from reported travel with only 2/1000 infected. Women traveling from heavily affected areas were most at risk for infection. Neonatal head circumference percentiles among infants born to women with evidence of possible Zika virus infection during pregnancy were not reduced when compared to infants born to women without infection. Copyright © 2017 Elsevier Inc. All rights reserved.

Evolutionary characterization of hemagglutinin gene of H9N2 influenza viruses isolated from Asia.

PubMed

Shahsavandi, Shahla; Salmanian, Ali-Hatef; Ghorashi, Seyed Ali; Masoudi, Shahin; Ebrahimi, Mohammad Majid

2012-08-01

The full length hemagglutinin (HA) genes of 287 H9N2 AI strains isolated from chickens in Asia during the period 1994-2009 were genetically analyzed. Phylogenetic analysis showed that G1-like viruses circulated in the Middle East and Indian sub-continent countries, whereas other sublineages existed in Far East countries. It also revealed G1-like viruses with an average 96.7% identity clustered into two subgroups largely based on their time of isolation. The Ka/Ks ratio was calculated 0.34 for subgroup 1 and 0.57 for subgroup 2 indicates purifying/stabilizing selection, but despite this there is evidence of localized positive selection when comparing the subgroups 1 and 2 protein sequences. Five sites in HA H9N2 viruses had a posterior probability >0.5 using the Bayesian method, indicating these sites were under positive selection. These sites were found to be associated with the globular head region of HA. To identify sites under positive selection; amino acid substitution classified depends on their radicalism and neutrality. The results indicate that, although most positions in HAs were under purifying selection and can be eliminated, a few positions located in the antigenic regions and receptor binding sites were subject to positive selection. Copyright © 2011 Elsevier Ltd. All rights reserved.

Origins and evolution of viruses of eukaryotes: The ultimate modularity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koonin, Eugene V., E-mail: koonin@ncbi.nlm.nih.gov; Dolja, Valerian V., E-mail: doljav@science.oregonstate.edu; Krupovic, Mart, E-mail: krupovic@pasteur.fr

2015-05-15

Viruses and other selfish genetic elements are dominant entities in the biosphere, with respect to both physical abundance and genetic diversity. Various selfish elements parasitize on all cellular life forms. The relative abundances of different classes of viruses are dramatically different between prokaryotes and eukaryotes. In prokaryotes, the great majority of viruses possess double-stranded (ds) DNA genomes, with a substantial minority of single-stranded (ss) DNA viruses and only limited presence of RNA viruses. In contrast, in eukaryotes, RNA viruses account for the majority of the virome diversity although ssDNA and dsDNA viruses are common as well. Phylogenomic analysis yields tangiblemore » clues for the origins of major classes of eukaryotic viruses and in particular their likely roots in prokaryotes. Specifically, the ancestral genome of positive-strand RNA viruses of eukaryotes might have been assembled de novo from genes derived from prokaryotic retroelements and bacteria although a primordial origin of this class of viruses cannot be ruled out. Different groups of double-stranded RNA viruses derive either from dsRNA bacteriophages or from positive-strand RNA viruses. The eukaryotic ssDNA viruses apparently evolved via a fusion of genes from prokaryotic rolling circle-replicating plasmids and positive-strand RNA viruses. Different families of eukaryotic dsDNA viruses appear to have originated from specific groups of bacteriophages on at least two independent occasions. Polintons, the largest known eukaryotic transposons, predicted to also form virus particles, most likely, were the evolutionary intermediates between bacterial tectiviruses and several groups of eukaryotic dsDNA viruses including the proposed order “Megavirales” that unites diverse families of large and giant viruses. Strikingly, evolution of all classes of eukaryotic viruses appears to have involved fusion between structural and replicative gene modules derived from different sources along with additional acquisitions of diverse genes. - Highlights: • Eukaryotic virome dramatically differs from the viromes of bacteria and archaea. • Eukaryotic virome is dominated by RNA viruses and retroelements. • All classes of eukaryotic viruses evolved by gene module exchange. • Prokaryotic ancestry is traceable for core gene modules of most eukaryotic viruses. • Evolutionary histories of viruses and transposable elements are tightly linked.« less

Hepatitis C virus infection and the risk of cancer among elderly US adults: A registry-based case-control study.

PubMed

Mahale, Parag; Torres, Harrys A; Kramer, Jennifer R; Hwang, Lu-Yu; Li, Ruosha; Brown, Eric L; Engels, Eric A

2017-04-01

Hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC) and subtypes of non-Hodgkin lymphoma (NHL). Associations with other cancers are not established. The authors systematically assessed associations between HCV infection and cancers in the US elderly population. This was a registry-based case-control study using Surveillance, Epidemiology, and End Results (SEER)-Medicare data in US adults aged ≥66 years. Cases (n = 1,623,538) were patients who had first cancers identified in SEER registries (1993-2011). Controls (n = 200,000) were randomly selected, cancer-free individuals who were frequency-matched to cases on age, sex, race, and calendar year. Associations with HCV (documented by Medicare claims) were determined using logistic regression. HCV prevalence was higher in cases than in controls (0.7% vs 0.5%). HCV was positively associated with cancers of the liver (adjusted odds ratio [aOR] = 31.5; 95% confidence interval [CI], 29.0-34.3), intrahepatic bile duct (aOR, 3.40; 95% CI, 2.52-4.58), extrahepatic bile duct (aOR, 1.90; 95% CI, 1.41-2.57), pancreas (aOR, 1.23; 95% CI, 1.09-1.40), and anus (aOR, 1.97; 95% CI, 1.42-2.73); nonmelanoma nonepithelial skin cancer (aOR, 1.53; 95% CI, 1.15-2.04); myelodysplastic syndrome (aOR, 1.56; 95% CI, 1.33-1.83); and diffuse large B-cell lymphoma (aOR, 1.57; 95% CI, 1.34-1.84). Specific skin cancers associated with HCV were Merkel cell carcinoma (aOR, 1.92; 95% CI, 1.30-2.85) and appendageal skin cancers (aOR, 2.02; 95% CI, 1.29-3.16). Inverse associations were observed with uterine cancer (aOR, 0.64; 95% CI, 0.51-0.80) and prostate cancer (aOR, 0.73; 95% CI, 0.66-0.82). Associations were maintained in sensitivity analyses conducted among individuals without documented alcohol abuse, cirrhosis, or hepatitis B or human immunodeficiency virus infections and after adjustment for socioeconomic status. Associations of HCV with other cancers were not observed. HCV is associated with increased risk of cancers other than HCC in the US elderly population, notably bile duct cancers and diffuse large B-cell lymphoma. These results support a possible etiologic role for HCV in an expanded group of cancers. Cancer 2017;123:1202-1211. © 2016 American Cancer Society. © 2017 American Cancer Society.

How's the Flu Getting Through? Landscape genetics suggests both humans and birds spread H5N1 in Egypt.

PubMed

Young, Sean G; Carrel, Margaret; Kitchen, Andrew; Malanson, George P; Tamerius, James; Ali, Mohamad; Kayali, Ghazi

2017-04-01

First introduced to Egypt in 2006, H5N1 highly pathogenic avian influenza has resulted in the death of millions of birds and caused over 350 infections and at least 117 deaths in humans. After a decade of viral circulation, outbreaks continue to occur and diffusion mechanisms between poultry farms remain unclear. Using landscape genetics techniques, we identify the distance models most strongly correlated with the genetic relatedness of the viruses, suggesting the most likely methods of viral diffusion within Egyptian poultry. Using 73 viral genetic sequences obtained from infected birds throughout northern Egypt between 2009 and 2015, we calculated the genetic dissimilarity between H5N1 viruses for all eight gene segments. Spatial correlation was evaluated using Mantel tests and correlograms and multiple regression of distance matrices within causal modeling and relative support frameworks. These tests examine spatial patterns of genetic relatedness, and compare different models of distance. Four models were evaluated: Euclidean distance, road network distance, road network distance via intervening markets, and a least-cost path model designed to approximate wild waterbird travel using niche modeling and circuit theory. Samples from backyard farms were most strongly correlated with least cost path distances. Samples from commercial farms were most strongly correlated with road network distances. Results were largely consistent across gene segments. Results suggest wild birds play an important role in viral diffusion between backyard farms, while commercial farms experience human-mediated diffusion. These results can inform avian influenza surveillance and intervention strategies in Egypt. Copyright © 2017 Elsevier B.V. All rights reserved.

Can the RNA of the cowpea chlorotic mottle virus be released through a channel by means of free diffusion? A test in silico.

PubMed

Isea, Raul; Aponte, Carlos; Cipriani, Roberto

2004-02-01

Cowpea chlorotic mottle virus (CCMV), a plant virus which is member of the Bromoviridae family, is used as a model for the diffusion of a random, short, single stranded RNA, [5'-R(PGpGpApCpUpUpCpGpGpUpCpC)-3')], through a channel on the pseudo-three-fold axis using molecular dynamic simulations. This proposition is based the fact that CCMV undergoes a dynamic structural transition as a response to changes of pH, temperature and ionic strength. Results indicate that the RNA looses its secondary structure and moves into the capside channel by free diffusion. These results are congruent with the hypothesis suggesting that the CCMV capside does not have to dissolve in order to release the RNA into the host.

Cotransport of clay colloids and viruses through water-saturated vertically oriented columns packed with glass beads: Gravity effects.

PubMed

Syngouna, Vasiliki I; Chrysikopoulos, Constantinos V

2016-03-01

The cotransport of clay colloids and viruses in vertically oriented laboratory columns packed with glass beads was investigated. Bacteriophages MS2 and ΦX174 were used as model viruses, and kaolinite (ΚGa-1b) and montmorillonite (STx-1b) as model clay colloids. A steady flow rate of Q=1.5 mL/min was applied in both vertical up (VU) and vertical down (VD) flow directions. In the presence of KGa-1b, estimated mass recovery values for both viruses were higher for VD than VU flow direction, while in the presence of STx-1b the opposite was observed. However, for all cases examined, the produced mass of viruses attached onto suspended clay particles were higher for VD than VU flow direction, suggesting that the flow direction significantly influences virus attachment onto clays, as well as packed column retention of viruses attached onto suspended clays. KGa-1b hindered the transport of ΦX174 under VD flow, while STx-1b facilitated the transport of ΦX174 under both VU and VD flow directions. Moreover, KGa-1b and STx-1b facilitated the transport of MS2 in most of the cases examined except of the case where KGa-1b was present under VD flow. Also, the experimental data were used for the estimation of virus surface-coverages and virus surface concentrations generated by virus diffusion-limited attachment, as well as virus attachment due to sedimentation. Both sedimentation and diffusion limited virus attachment were higher for VD than VU flow, except the case of MS2 and STx-1b cotransport. The diffusion-limited attachment was higher for MS2 than ΦΧ174 for all cases examined. Copyright © 2015 Elsevier B.V. All rights reserved.

Accumulation of a 5’ proximal subgenomic RNA of Citrus tristeza virus is correlated with encapsidation by the minor coat protein

USDA-ARS?s Scientific Manuscript database

During replication, Citrus tristeza virus (CTV) produces large amounts of two unusual subgenomic (sg) RNAs that are positive-stranded and 5' -coterminal. Although these RNAs are produced in similar amounts and are similar in size, with LMT1 (~750 nt) only slightly larger than LMT2 (~650), we found ...

Rift Valley fever on the east coast of Madagascar.

PubMed

Morvan, J; Saluzzo, J F; Fontenille, D; Rollin, P E; Coulanges, P

1991-01-01

In March 1990, a Rift Valley fever virus (RVFV) outbreak was suspected in the district of Fenerive on the east coast of Madagascar after an abnormally high incidence of abortions and disease in livestock. Sera from humans and cattle were tested for RVFV antibodies by immunofluorescence assay (IFA) and ELISA-IgM capture. Sera and mosquitoes collected in the same area were tested for virus isolation by tissue culture and suckling mouse intracerebral inoculation, and for antigen detection by an ELISA antigen capture assay. Among cattle from the area, RVFV antibody prevalence was 58.6% by IFA and 29.6% by ELISA-IgM. In contrast, human populations in the same area had a lower RVFV antibody prevalence, with 8.01% IFA and 5.4% IgM-positive sera. No RVFV antigen was detected and virus isolation was unsuccessful from the sera and mosquito pools tested. Different hypotheses concerning the emergence and diffusion of RVFV in this area and the occurrence of the outbreak are discussed.

A Signature in HIV-1 Envelope Leader Peptide Associated with Transition from Acute to Chronic Infection Impacts Envelope Processing and Infectivity

PubMed Central

Asmal, Mohammed; Hellmann, Ina; Liu, Weimin; Keele, Brandon F.; Perelson, Alan S.; Bhattacharya, Tanmoy; Gnanakaran, S.; Daniels, Marcus; Haynes, Barton F.; Korber, Bette T.; Hahn, Beatrice H.; Shaw, George M.; Letvin, Norman L.

2011-01-01

Mucosal transmission of the human immunodeficiency virus (HIV) results in a bottleneck in viral genetic diversity. Gnanakaran and colleagues used a computational strategy to identify signature amino acids at particular positions in Envelope that were associated either with transmitted sequences sampled very early in infection, or sequences sampled during chronic infection. Among the strongest signatures observed was an enrichment for the stable presence of histidine at position 12 at transmission and in early infection, and a recurrent loss of histidine at position 12 in chronic infection. This amino acid lies within the leader peptide of Envelope, a region of the protein that has been shown to influence envelope glycoprotein expression and virion infectivity. We show a strong association between a positively charged amino acid like histidine at position 12 in transmitted/founder viruses with more efficient trafficking of the nascent envelope polypeptide to the endoplasmic reticulum and higher steady-state glycoprotein expression compared to viruses that have a non-basic position 12 residue, a substitution that was enriched among viruses sampled from chronically infected individuals. When expressed in the context of other viral proteins, transmitted envelopes with a basic amino acid position 12 were incorporated at higher density into the virus and exhibited higher infectious titers than did non-signature envelopes. These results support the potential utility of using a computational approach to examine large viral sequence data sets for functional signatures and indicate the importance of Envelope expression levels for efficient HIV transmission. PMID:21876761

[Effects of resting days on live poultry markets in controlling the avian influenza pollution].

PubMed

Liu, Hui; Chen, Zongqiu; Xiao, Xincai; Lu, Jianyun; Di, Biao; Li, Kuibiao; Wang, Hui; Luo, Lei; Yang, Zhicong

2014-07-01

To analyze the results of nine-round environmental specimen surveillance programs in five live poultry markets pre-, during and post the 'closing days' and to evaluate the effects of 'closing days' on live poultry markets regarding the control against avian influenza pollution. In January 2014, control measures including culling poultry, completely cleaning and disinfecting and a 'three-day-closing' measure were conducted in five live poultry markets which were found positive for H7N9 nucleic acid in the 1(st) round environmental specimen surveillance program. Second surveillance program was conducted after a thorough disinfection campaign was launched. Several times surveillance were conducted in one week, after the markets were reopened. RT-PCR was used to test the nucleic acid of HA, H5, H7 and H9 viruses. 654 specimens from the environment were collected and tested. During the first round surveillance program, positive rates for influenza A and H5/H7/H9 nucleic acid of poultry stalls appeared to be 94.44% and 61.11% respectively. The positive rates of poultry stalls reduced to 0 after the disinfection campaign but increased again after the markets reopened. The positive rate for influenza A of poultry stalls slightly increased from 50.00% in the third surveillance to 72.22% in the ninth surveillance (P > 0.05). The positive rate for H5/H7/H9 of poultry stalls showed a significantly increasing trend, from 0 in the third surveillance to 44.44% in the ninth surveillance (P < 0.01). The positive rates for influenza A and H5/H7/H9 nucleic acid of specimens were 28.89% and 17.78% respectively. The positive rate of specimens reduced to 0 after disinfection while increased again after reopening of the markets. The positive rate for influenza A of specimens slightly increased from 19.67% in the third surveillance to 27.54% in the ninth surveillance programs (P > 0.05). The positive rate for H5/H7/H9 of specimen showed a significant increasing trend, from 0 in the third surveillance to 8.70% in the ninth-round surveillance programs (P < 0.01). The positive rate for influenza A was the highest for slaughter- related specimens of 22.4% (35/156). The positive rates for influenza A from sewage and drinking water being collected on the later stage after the markets reopened (25.9%, 12.4%)were higher than those on the early stage (8.3%, 8.6%) (P > 0.05). The positive rate for influenza A of poultry stalls with overnight poultry storage (91.7%) was significant higher than that of poultry stalls without the overnight storage (33.3%). The positive rate for influenza A of poultry stalls in which simultaneously selling different kinds of poultry (85.7%) was significant higher than that of poultry stalls in which selling only one kind of poultry at one time (25.0%) (P < 0.05). Slaughter in live poultry markets posed a large risk of pollution diffusion. Sewage and drinking water showed an accumulation effect for avian influenza virus. Overnight poultry storage and selling different kinds of poultry at one time at the poultry stalls seemed the risk factors for avian influenza virus transmission. Complete cleaning, disinfecting and several 'closing days' for live poultry markets seemed effective in eliminating avian influenza virus. Once the markets were reopened, they seemed to be soon polluted again.

Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas

ClinicalTrials.gov

2015-04-28

Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Epstein-Barr Virus Infection; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Untreated Hairy Cell Leukemia; Waldenström Macroglobulinemia

Complete genome sequencing and evolutionary phylogeography analysis of Indian isolates of Dengue virus type 1.

PubMed

Dash, Paban Kumar; Sharma, Shashi; Soni, Manisha; Agarwal, Ankita; Sahni, Ajay Kumar; Parida, Manmohan

2015-01-02

Dengue is now hyper-endemic in most parts of south and southeast Asia including India. The northern India particularly national capital New Delhi witnessed major Dengue outbreaks with Dengue virus type 1 (DENV-1) as the dominant serotype since last five years. This study was initiated to decipher the complete genome information of recently circulating DENV-1 (2009-2011) along with the prototype Indian DENV-1, isolated in 1956. Further extensive ML phylogenetic and Bayesian phylogeography analysis was carried out to investigate the evolution of this virus and understand its spatiotemporal diffusion across the globe. The complete genome analysis revealed deletion of a unique 21-nucleotide stretch in the 3' un-translated region of recent Indian DENV-1. The north Indian DENV-1 revealed up to 5.2% nucleotide sequence difference compared to recent isolates from southern India. Selection pressure analysis revealed positive selection in few amino acid sites of both structural and non-structural proteins. The molecular phylogeny classified the Indian DENV-1 into genotype III, which is also known as cosmopolitan genotype. The northern and southern Indian DENV-1 were grouped into distinct clades. The molecular clock analysis estimated a mean evolutionary rate of 7.08×10(-4) substitutions/site/year for cosmopolitan genotype. The phylogeography analysis revealed that the cosmopolitan genotype DENV-1 originated ∼1938 in India and subsequently spread globally. The diffusion of virus from India to Caribbean and South America was confirmed through SPREAD analysis. This study also confirmed the temporal displacement of different clades of DENV-1 in India over last five decades. Copyright © 2014 Elsevier B.V. All rights reserved.

The Neck Region of the C-type Lectin DC-SIGN Regulates Its Surface Spatiotemporal Organization and Virus-binding Capacity on Antigen-presenting Cells*

PubMed Central

Manzo, Carlo; Torreno-Pina, Juan A.; Joosten, Ben; Reinieren-Beeren, Inge; Gualda, Emilio J.; Loza-Alvarez, Pablo; Figdor, Carl G.; Garcia-Parajo, Maria F.; Cambi, Alessandra

2012-01-01

The C-type lectin DC-SIGN expressed on dendritic cells (DCs) facilitates capture and internalization of a plethora of different pathogens. Although it is known that DC-SIGN organizes in nanoclusters at the surface of DCs, the molecular mechanisms responsible for this well defined nanopatterning and role in viral binding remain enigmatic. By combining biochemical and advanced biophysical techniques, including optical superresolution and single particle tracking, we demonstrate that DC-SIGN intrinsic nanoclustering strictly depends on its molecular structure. DC-SIGN nanoclusters exhibited free, Brownian diffusion on the cell membrane. Truncation of the extracellular neck region, known to abrogate tetramerization, significantly reduced nanoclustering and concomitantly increased lateral diffusion. Importantly, DC-SIGN nanocluster dissolution exclusively compromised binding to nanoscale size pathogens. Monte Carlo simulations revealed that heterogeneity on nanocluster density and spatial distribution confers broader binding capabilities to DC-SIGN. As such, our results underscore a direct relationship between spatial nanopatterning, driven by intermolecular interactions between the neck regions, and receptor diffusion to provide DC-SIGN with the exquisite ability to dock pathogens at the virus length scale. Insight into how virus receptors are organized prior to virus binding and how they assemble into functional platforms for virus docking is helpful to develop novel strategies to prevent virus entry and infection. PMID:23019323

Comparative Genomics of Amphibian-like Ranaviruses, Nucleocytoplasmic Large DNA Viruses of Poikilotherms

PubMed Central

Price, Stephen J.

2015-01-01

Recent research on genome evolution of large DNA viruses has highlighted a number of incredibly dynamic processes that can facilitate rapid adaptation. The genomes of amphibian-like ranaviruses – double-stranded DNA viruses infecting amphibians, reptiles, and fish (family Iridoviridae) – were examined to assess variation in genome content and evolutionary processes. The viruses studied were closely related, but their genome content varied considerably, with 29 genes identified that were not present in all of the major clades. Twenty-one genes had evidence of recombination, while a virus isolated from a captive reptile appeared to be a mosaic of two divergent parents. Positive selection was also found to be acting on more than a quarter of Ranavirus genes and was found most frequently in the Spanish common midwife toad virus, which has had a severe impact on amphibian host communities. Efforts to resolve the root of this group by inclusion of an outgroup were inconclusive, but a set of core genes were identified, which recovered a well-supported species tree. PMID:27812275

The conundrum of the Epstein-Barr virus-associated gastric carcinoma in the Americas

PubMed Central

Carrasco-Avino, Gonzalo; Riquelme, Ismael; Padilla, Oslando; Villaseca, Miguel; Aguayo, Francisco R.; Corvalan, Alejandro H.

2017-01-01

Epstein-Barr virus-associated gastric carcinoma shows a higher prevalence in the Americas than Asia. We summarize all studies of Epstein Barr virus-associated gastric carcinoma in the Americas, focusing on host characteristics, environmental associations and phylogeographic diversity of Epstein-Barr virus strains. In the Americas, the prevalence of Epstein Barr virus-associated gastric carcinoma is 11.4%, more frequent in males and portray predominantly diffuse-type histology. EBERs, EBNAs, BARTs and LMP are the highest expressed genes; their variations in healthy individuals may explain the phylogeographic diversity of Epstein-Barr virus across the region. Gastric cancer cases harbor exclusively the western genotype (subtype D and kept Xho I site), suggesting a disrupted co-evolution between the pathogen and its host. Epstein-Barr virus-associated gastric carcinoma molecular subtype cases from The Cancer Genome Atlas display PIK3CA gene mutations, amplification of JAK2, PD-L1 and PD-L2 and CpG island methylator phenotype, leading to more extensive methylation of host and viral genomes than any other subtypes from the study. Environmental conditions include negative- and positive- associations with being firstborn child and smoking, respectively. A marginal association with H. pylori has also been reported. Lymphoepithelioma-like carcinoma is associated with Epstein Barr virus in 80%–86% of cases, most of which have been included as part of Epstein Barr virus-associated gastric carcinoma series (prevalence 1.1%–7.6%). Whether these cases represent a variant of Epstein-Barr virus-associated gastric carcinoma is discussed. We propose novel research strategies to solve the conundrum of the high prevalence of Epstein-Barr virus-associated gastric carcinoma in the Americas. PMID:29088902

Febrile status epilepticus due to respiratory syncytial virus infection.

PubMed

Uda, Kazuhiro; Kitazawa, Katsuhiko

2017-08-01

Febrile status epilepticus can have neurological sequelae. The type of sequelae, however, depend on the etiology, including infection due to viral agents such as the influenza virus. Respiratory syncytial virus (RSV) infection in childhood may also contribute to this. The aim of this study was therefore to characterize febrile status epilepticus associated with RSV infection, and to determine whether this type of infection is a risk factor for neurological sequelae in febrile status epilepticus. We reviewed the medical records of children aged ≤3 years with febrile status epilepticus who were admitted to a tertiary hospital between January 2007 and December 2011. The differences between the RSV-positive and RSV-negative groups were evaluated according to the demographic and clinical data. A total of 99 patients with febrile status epilepticus who had been tested for RSV infection were identified. Three patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n = 80) presented with bronchiolitis. The incidence of intubation and anti-seizure drug treatment in the RSV-positive group was significantly higher than in the -negative group. While all of the patients in the RSV-negative group recovered completely, six patients in the RSV-positive group developed encephalopathy and profound neurological sequelae. In five of the six patients, diffusion-weighted magnetic resonance imaging showed subcortical white matter lesions. RSV infection in the absence of bronchiolitis can initially present as febrile status epilepticus and subsequently develop into acute encephalopathy with profound neurological sequelae. © 2017 Japan Pediatric Society.

Time scale of random sequential adsorption.

PubMed

Erban, Radek; Chapman, S Jonathan

2007-04-01

A simple multiscale approach to the diffusion-driven adsorption from a solution to a solid surface is presented. The model combines two important features of the adsorption process: (i) The kinetics of the chemical reaction between adsorbing molecules and the surface and (ii) geometrical constraints on the surface made by molecules which are already adsorbed. The process (i) is modeled in a diffusion-driven context, i.e., the conditional probability of adsorbing a molecule provided that the molecule hits the surface is related to the macroscopic surface reaction rate. The geometrical constraint (ii) is modeled using random sequential adsorption (RSA), which is the sequential addition of molecules at random positions on a surface; one attempt to attach a molecule is made per one RSA simulation time step. By coupling RSA with the diffusion of molecules in the solution above the surface the RSA simulation time step is related to the real physical time. The method is illustrated on a model of chemisorption of reactive polymers to a virus surface.

Pericarditis mediated by respiratory syncytial virus in a hematopoietic stem cell transplant patient.

PubMed

Rubach, M P; Pavlisko, E N; Perfect, J R

2013-08-01

We describe a case of pericarditis and large pericardial effusion in a 63-year-old African-American man undergoing autologous hematopoietic stem cell transplant for multiple myeloma. Pericardial tissue biopsy demonstrated fibrinous pericarditis, and immunohistochemistry stains were positive for respiratory syncytial virus. The patient improved with oral ribavirin and intravenous immune globulin infusions. © 2013 John Wiley & Sons A/S.

Molecular Epidemiology and Evolution of Influenza Viruses Circulating within European Swine between 2009 and 2013.

PubMed

Watson, Simon J; Langat, Pinky; Reid, Scott M; Lam, Tommy Tsan-Yuk; Cotten, Matthew; Kelly, Michael; Van Reeth, Kristien; Qiu, Yu; Simon, Gaëlle; Bonin, Emilie; Foni, Emanuela; Chiapponi, Chiara; Larsen, Lars; Hjulsager, Charlotte; Markowska-Daniel, Iwona; Urbaniak, Kinga; Dürrwald, Ralf; Schlegel, Michael; Huovilainen, Anita; Davidson, Irit; Dán, Ádám; Loeffen, Willie; Edwards, Stephanie; Bublot, Michel; Vila, Thais; Maldonado, Jaime; Valls, Laura; Brown, Ian H; Pybus, Oliver G; Kellam, Paul

2015-10-01

The emergence in humans of the A(H1N1)pdm09 influenza virus, a complex reassortant virus of swine origin, highlighted the importance of worldwide influenza virus surveillance in swine. To date, large-scale surveillance studies have been reported for southern China and North America, but such data have not yet been described for Europe. We report the first large-scale genomic characterization of 290 swine influenza viruses collected from 14 European countries between 2009 and 2013. A total of 23 distinct genotypes were identified, with the 7 most common comprising 82% of the incidence. Contrasting epidemiological dynamics were observed for two of these genotypes, H1huN2 and H3N2, with the former showing multiple long-lived geographically isolated lineages, while the latter had short-lived geographically diffuse lineages. At least 32 human-swine transmission events have resulted in A(H1N1)pdm09 becoming established at a mean frequency of 8% across European countries. Notably, swine in the United Kingdom have largely had a replacement of the endemic Eurasian avian virus-like ("avian-like") genotypes with A(H1N1)pdm09-derived genotypes. The high number of reassortant genotypes observed in European swine, combined with the identification of a genotype similar to the A(H3N2)v genotype in North America, underlines the importance of continued swine surveillance in Europe for the purposes of maintaining public health. This report further reveals that the emergences and drivers of virus evolution in swine differ at the global level. The influenza A(H1N1)pdm09 virus contains a reassortant genome with segments derived from separate virus lineages that evolved in different regions of the world. In particular, its neuraminidase and matrix segments were derived from the Eurasian avian virus-like ("avian-like") lineage that emerged in European swine in the 1970s. However, while large-scale genomic characterization of swine has been reported for southern China and North America, no equivalent study has yet been reported for Europe. Surveillance of swine herds across Europe between 2009 and 2013 revealed that the A(H1N1)pdm09 virus is established in European swine, increasing the number of circulating lineages in the region and increasing the possibility of the emergence of a genotype with human pandemic potential. It also has implications for veterinary health, making prevention through vaccination more challenging. The identification of a genotype similar to the A(H3N2)v genotype, causing zoonoses at North American agricultural fairs, underlines the importance of continued genomic characterization in European swine. Copyright © 2015 Watson et al.

Molecular Epidemiology and Evolution of Influenza Viruses Circulating within European Swine between 2009 and 2013

PubMed Central

Watson, Simon J.; Langat, Pinky; Reid, Scott M.; Lam, Tommy Tsan-Yuk; Cotten, Matthew; Kelly, Michael; Van Reeth, Kristien; Qiu, Yu; Simon, Gaëlle; Bonin, Emilie; Foni, Emanuela; Chiapponi, Chiara; Larsen, Lars; Hjulsager, Charlotte; Markowska-Daniel, Iwona; Urbaniak, Kinga; Dürrwald, Ralf; Schlegel, Michael; Huovilainen, Anita; Davidson, Irit; Dán, Ádám; Loeffen, Willie; Edwards, Stephanie; Bublot, Michel; Vila, Thais; Maldonado, Jaime; Valls, Laura; Brown, Ian H.; Pybus, Oliver G.

2015-01-01

ABSTRACT The emergence in humans of the A(H1N1)pdm09 influenza virus, a complex reassortant virus of swine origin, highlighted the importance of worldwide influenza virus surveillance in swine. To date, large-scale surveillance studies have been reported for southern China and North America, but such data have not yet been described for Europe. We report the first large-scale genomic characterization of 290 swine influenza viruses collected from 14 European countries between 2009 and 2013. A total of 23 distinct genotypes were identified, with the 7 most common comprising 82% of the incidence. Contrasting epidemiological dynamics were observed for two of these genotypes, H1huN2 and H3N2, with the former showing multiple long-lived geographically isolated lineages, while the latter had short-lived geographically diffuse lineages. At least 32 human-swine transmission events have resulted in A(H1N1)pdm09 becoming established at a mean frequency of 8% across European countries. Notably, swine in the United Kingdom have largely had a replacement of the endemic Eurasian avian virus-like (“avian-like”) genotypes with A(H1N1)pdm09-derived genotypes. The high number of reassortant genotypes observed in European swine, combined with the identification of a genotype similar to the A(H3N2)v genotype in North America, underlines the importance of continued swine surveillance in Europe for the purposes of maintaining public health. This report further reveals that the emergences and drivers of virus evolution in swine differ at the global level. IMPORTANCE The influenza A(H1N1)pdm09 virus contains a reassortant genome with segments derived from separate virus lineages that evolved in different regions of the world. In particular, its neuraminidase and matrix segments were derived from the Eurasian avian virus-like (“avian-like”) lineage that emerged in European swine in the 1970s. However, while large-scale genomic characterization of swine has been reported for southern China and North America, no equivalent study has yet been reported for Europe. Surveillance of swine herds across Europe between 2009 and 2013 revealed that the A(H1N1)pdm09 virus is established in European swine, increasing the number of circulating lineages in the region and increasing the possibility of the emergence of a genotype with human pandemic potential. It also has implications for veterinary health, making prevention through vaccination more challenging. The identification of a genotype similar to the A(H3N2)v genotype, causing zoonoses at North American agricultural fairs, underlines the importance of continued genomic characterization in European swine. PMID:26202246

Semi-analytical study of the tokamak pedestal density profile in a single-null diverted plasma with puffing-recycling gas sources

NASA Astrophysics Data System (ADS)

Shi, Bingren

2010-10-01

The tokamak pedestal density structure is generally studied using a diffusion-dominant model. Recent investigations (Stacey and Groebner 2009 Phys. Plasmas 16 102504) from first principle based physics have shown a plausible existence of large inward convection in the pedestal region. The diffusion-convection equation with rapidly varying convection and diffusion coefficients in the near edge region and model puffing-recycling neutral particles is studied in this paper. A peculiar property of its solution for the existence of the large convection case is that the pedestal width of the density profile, qualitatively different from the diffusion-dominant case, depends mainly on the width of the inward convection and only weakly on the neutral penetration length and its injection position.

Nonlinear diffusion and viral spread through the leaf of a plant

NASA Astrophysics Data System (ADS)

Edwards, Maureen P.; Waterhouse, Peter M.; Munoz-Lopez, María Jesús; Anderssen, Robert S.

2016-10-01

The spread of a virus through the leaf of a plant is both spatially and temporally causal in that the present status depends on the past and the spatial spread is compactly supported and progresses outwards. Such spatial spread is known to occur for certain nonlinear diffusion processes. The first compactly supported solution for nonlinear diffusion equations appears to be that of Pattle published in 1959. In that paper, no explanation is given as to how the solution was derived. Here, we show how the solution can be derived using Lie symmetry analysis. This lays a foundation for exploring the behavior of other choices for nonlinear diffusion and exploring the addition of reaction terms which do not eliminate the compactly supported structure. The implications associated with using the reaction-diffusion equation to model the spatial-temporal spread of a virus through the leaf of a plant are discussed.

A model of partial differential equations for HIV propagation in lymph nodes

NASA Astrophysics Data System (ADS)

Marinho, E. B. S.; Bacelar, F. S.; Andrade, R. F. S.

2012-01-01

A system of partial differential equations is used to model the dissemination of the Human Immunodeficiency Virus (HIV) in CD4+T cells within lymph nodes. Besides diffusion terms, the model also includes a time-delay dependence to describe the time lag required by the immunologic system to provide defenses to new virus strains. The resulting dynamics strongly depends on the properties of the invariant sets of the model, consisting of three fixed points related to the time independent and spatial homogeneous tissue configurations in healthy and infected states. A region in the parameter space is considered, for which the time dependence of the space averaged model variables follows the clinical pattern reported for infected patients: a short scale primary infection, followed by a long latency period of almost complete recovery and third phase characterized by damped oscillations around a value with large HIV counting. Depending on the value of the diffusion coefficient, the latency time increases with respect to that one obtained for the space homogeneous version of the model. It is found that same initial conditions lead to quite different spatial patterns, which depend strongly on the latency interval.

HIV and hepatitis C virus RNA in seronegative organ and tissue donors.

PubMed

Challine, Dominique; Pellegrin, Bertrand; Bouvier-Alias, Magali; Rigot, Pierrette; Laperche, Liliane; Pawlotsky, Jean-Michel

The objective of our study was to determine whether nucleic acid testing could detect HIV RNA or hepatitis C virus (HCV) RNA in a large series of seronegative organ and tissue donors, and whether this technique should be routinely used to improve viral safety of grafts. We studied 2236 organ donors, 636 tissue donors, and 177 cornea donors. We identified five HCV RNA-positive donors in 2119 HCV-seronegative organ donors, and one HCV RNA-positive donor in 631 HCV-seronegative tissue donors. No HIV-seronegative, HIV RNA-positive donor was identified. Our data suggest that routine nucleic acid testing of organ and tissue donors might increase viral safety in transplantation.

Clinical presentation and laboratory findings for the first autochthonous cases of dengue fever in Madeira island, Portugal, October 2012.

PubMed

Alves, M J; Fernandes, P L; Amaro, F; Osório, H; Luz, T; Parreira, P; Andrade, G; Zé-Zé, L; Zeller, H

2013-02-07

An outbreak of dengue fever in Madeira island was reported in 2012. Clinical and laboratory findings of the first two laboratory-confirmed autochthonous cases are reported. Both cases had fever (≥38 °C) and petechial rash. Symptoms also included myalgia, asthenia, nausea, vomiting, anorexia, diffuse abdominal pain, and diarrhoea. The two cases were confirmed by serology and one tested positive for a dengue viral sequence. Dengue virus serotype DEN-1 was identified with probable Central or South American origin.

Electron radiography

DOEpatents

Merrill, Frank E.; Morris, Christopher

2005-05-17

A system capable of performing radiography using a beam of electrons. Diffuser means receive a beam of electrons and diffuse the electrons before they enter first matching quadrupoles where the diffused electrons are focused prior to the diffused electrons entering an object. First imaging quadrupoles receive the focused diffused electrons after the focused diffused electrons have been scattered by the object for focusing the scattered electrons. Collimator means receive the scattered electrons and remove scattered electrons that have scattered to large angles. Second imaging quadrupoles receive the collimated scattered electrons and refocus the collimated scattered electrons and map the focused collimated scattered electrons to transverse locations on an image plane representative of the electrons' positions in the object.

Knockout of Epstein-Barr Virus BPLF1 Retards B-Cell Transformation and Lymphoma Formation in Humanized Mice

PubMed Central

Li, Guangming; Montgomery, Stephanie A.; Montgomery, Nathan D.; Su, Lishan; Pagano, Joseph S.

2015-01-01

ABSTRACT BPLF1 of Epstein-Barr virus (EBV) is classified as a late lytic cycle protein but is also found in the viral tegument, suggesting its potential involvement at both initial and late stages of viral infection. BPLF1 possesses both deubiquitinating and deneddylating activity located in its N-terminal domain and is involved in processes that affect viral infectivity, viral DNA replication, DNA repair, and immune evasion. A recently constructed EBV BPLF1-knockout (KO) virus was used in conjunction with a humanized mouse model that can be infected with EBV, enabling the first characterization of BPLF1 function in vivo. Results demonstrate that the BPLF1-knockout virus is approximately 90% less infectious than wild-type (WT) virus. Transformation of human B cells, a hallmark of EBV infection, was delayed and reduced with BPLF1-knockout virus. Humanized mice infected with EBV BPLF1-knockout virus showed less weight loss and survived longer than mice infected with equivalent infectious units of WT virus. Additionally, splenic tumors formed in 100% of mice infected with WT EBV but in only 25% of mice infected with BPLF1-KO virus. Morphological features of spleens containing tumors were similar to those in EBV-induced posttransplant lymphoproliferative disease (PTLD) and were almost identical to cases seen in human diffuse large B-cell lymphoma. The presence of EBV genomes was detected in all mice that developed tumors. The results implicate BPLF1 in human B-cell transformation and tumor formation in humanized mice. PMID:26489865

Hydrogen diffusion in liquid aluminum from ab initio molecular dynamics

NASA Astrophysics Data System (ADS)

Jakse, N.; Pasturel, A.

2014-05-01

Ab initio molecular dynamics simulations are used to describe the diffusion of hydrogen in liquid aluminum at different temperatures. Quasi-instantaneous jumps separating periods of localized vibrations around a mean position are found to characterize the hydrogen motion at the microscopic scale. The hydrogen motion is furthermore analyzed using the van Hove function. We highlight a non-Fickian behavior for the hydrogen diffusion due to a large spatial distribution of hydrogen jumps. We show that a generalized continuous time random walk (CTRW) model describes the experimental diffusion coefficients in a satisfactory manner. Finally, the impact of impurities and alloying elements on hydrogen diffusion in aluminum is discussed.

A Physical Mechanism for the Asymmetry in Top-Down and Bottom-Up Diffusion.

NASA Astrophysics Data System (ADS)

Wyngaard, J. C.

1987-04-01

Recent large-eddy simulations of the vertical diffusion of a passive, conservative scalar through the convective boundary layer (CBL) show strikingly different eddy diffusivity profiles in the `top-down' and `bottom-up' cases. These results indicate that for a given turbulent velocity field and associated scalar flux, the mean change in scalar mixing ratio across the CBL is several times larger if the flux originates at the top of the boundary layer (i.e., in top-down diffusion) rather than at the bottom. The large-eddy simulation (LES) data show that this asymmetry is due to a breakdown of the eddy-diffusion concept.A simple updraft-downdraft model of the CBL reveals a physical mechanism that could cause this unexpected behavior. The large, positive skewness of the convectively driven vertical velocity gives an appreciably higher probability of downdrafts than updrafts; this excess probability of downdrafts, interacting with the time changes of the mean mixing ratio caused by the nonstationarity of the bottom-up and top-down diffusion processes, decreases the equilibrium value of mean mixing-ratio jump across the mixed layer in the bottom-up case and increases it in the top-down case. The resulting diffusion asymmetry agrees qualitatively with that found through LES.

Genome-Wide Networks of Amino Acid Covariances Are Common among Viruses

PubMed Central

Donlin, Maureen J.; Szeto, Brandon; Gohara, David W.; Aurora, Rajeev

2012-01-01

Coordinated variation among positions in amino acid sequence alignments can reveal genetic dependencies at noncontiguous positions, but methods to assess these interactions are incompletely developed. Previously, we found genome-wide networks of covarying residue positions in the hepatitis C virus genome (R. Aurora, M. J. Donlin, N. A. Cannon, and J. E. Tavis, J. Clin. Invest. 119:225–236, 2009). Here, we asked whether such networks are present in a diverse set of viruses and, if so, what they may imply about viral biology. Viral sequences were obtained for 16 viruses in 13 species from 9 families. The entire viral coding potential for each virus was aligned, all possible amino acid covariances were identified using the observed-minus-expected-squared algorithm at a false-discovery rate of ≤1%, and networks of covariances were assessed using standard methods. Covariances that spanned the viral coding potential were common in all viruses. In all cases, the covariances formed a single network that contained essentially all of the covariances. The hepatitis C virus networks had hub-and-spoke topologies, but all other networks had random topologies with an unusually large number of highly connected nodes. These results indicate that genome-wide networks of genetic associations and the coordinated evolution they imply are very common in viral genomes, that the networks rarely have the hub-and-spoke topology that dominates other biological networks, and that network topologies can vary substantially even within a given viral group. Five examples with hepatitis B virus and poliovirus are presented to illustrate how covariance network analysis can lead to inferences about viral biology. PMID:22238298

[A case of human infection with highly pathogenic avian influenza A (H7N9) virus through poultry processing without protection measure].

PubMed

Ma, Y; Zhang, Z B; Cao, L; Lu, J Y; Li, K B; Su, W Z; Li, T G; Yang, Z C; Wang, M

2018-06-10

Objective: To investigate the infection pattern and etiological characteristics of a case of human infection with highly pathogenic avian influenza A (H7N9) virus and provide evidence for the prevention and control of human infection with highly pathogenic avian influenza virus. Methods: Epidemiological investigation was conducted to explore the case's exposure history, infection route and disease progression. Samples collected from the patient, environments and poultry were tested by using real time reverse transcriptase-polymerase chain reaction (RT-PCR). Virus isolation, genome sequencing and phylogenetic analysis were conducted for positive samples. Results: The case had no live poultry contact history, but had a history of pulled chicken processing without taking protection measure in an unventilated kitchen before the onset. Samples collected from the patient's lower respiratory tract, the remaining frozen chicken meat and the live poultry market were all influenza A (H7N9) virus positive. The isolated viruses from these positive samples were highly homogenous. An insertion which lead to the addition of multiple basic amino acid residues (PEVPKRKRTAR/GL) was found at the HA cleavage site, suggesting that this virus might be highly pathogenic. Conclusions: Live poultry processing without protection measure is an important infection mode of "poultry to human" transmission of avian influenza viruses. Due to the limitation of protection measures in live poultry markets in Guangzhou, it is necessary to promote the standardized large scale poultry farming, the complete restriction of live poultry sales and centralized poultry slaughtering as well as ice fresh sale.

No evidence of persisting measles virus in peripheral blood mononuclear cells from children with autism spectrum disorder.

PubMed

D'Souza, Yasmin; Fombonne, Eric; Ward, Brian J

2006-10-01

Despite epidemiologic evidence to the contrary, claims of an association between measles-mumps-rubella vaccination and the development of autism have persisted. Such claims are based primarily on the identification of measles virus nucleic acids in tissues and body fluids by polymerase chain reaction. We sought to determine whether measles virus nucleic acids persist in children with autism spectrum disorder compared with control children. Peripheral blood mononuclear cells were isolated from 54 children with autism spectrum disorder and 34 developmentally normal children, and up to 4 real-time polymerase chain reaction assays and 2 nested polymerase chain reaction assays were performed. These assays targeted the nucleoprotein, fusion, and hemagglutinin genes of measles virus using previously published primer pairs with detection by SYBR green I. Our own real-time assay targeted the fusion gene using novel primers and an internal fluorescent probe. Positive reactions were evaluated rigorously, and amplicons were sequenced. Finally, anti-measles antibody titers were measured by enzyme immunoassay. The real-time assays based on previously published primers gave rise to a large number of positive reactions in both autism spectrum disorder and control samples. Almost all of the positive reactions in these assays were eliminated by evaluation of melting curves and amplicon band size. The amplicons for the remaining positive reactions were cloned and sequenced. No sample from either autism spectrum disorder or control groups was found to contain nucleic acids from any measles virus gene. In the nested polymerase chain reaction and in-house assays, none of the samples yielded positive results. Furthermore, there was no difference in anti-measles antibody titers between the autism and control groups. There is no evidence of measles virus persistence in the peripheral blood mononuclear cells of children with autism spectrum disorder.

Neurotropic Enterovirus Infections in the Central Nervous System.

PubMed

Huang, Hsing-I; Shih, Shin-Ru

2015-11-24

Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS) and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells.

Neurotropic Enterovirus Infections in the Central Nervous System

PubMed Central

Huang, Hsing-I; Shih, Shin-Ru

2015-01-01

Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS) and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells. PMID:26610549

Large-Scale Genomic Analysis of Codon Usage in Dengue Virus and Evaluation of Its Phylogenetic Dependence

PubMed Central

Lara-Ramírez, Edgar E.; Salazar, Ma Isabel; López-López, María de Jesús; Salas-Benito, Juan Santiago; Sánchez-Varela, Alejandro

2014-01-01

The increasing number of dengue virus (DENV) genome sequences available allows identifying the contributing factors to DENV evolution. In the present study, the codon usage in serotypes 1–4 (DENV1–4) has been explored for 3047 sequenced genomes using different statistics methods. The correlation analysis of total GC content (GC) with GC content at the three nucleotide positions of codons (GC1, GC2, and GC3) as well as the effective number of codons (ENC, ENCp) versus GC3 plots revealed mutational bias and purifying selection pressures as the major forces influencing the codon usage, but with distinct pressure on specific nucleotide position in the codon. The correspondence analysis (CA) and clustering analysis on relative synonymous codon usage (RSCU) within each serotype showed similar clustering patterns to the phylogenetic analysis of nucleotide sequences for DENV1–4. These clustering patterns are strongly related to the virus geographic origin. The phylogenetic dependence analysis also suggests that stabilizing selection acts on the codon usage bias. Our analysis of a large scale reveals new feature on DENV genomic evolution. PMID:25136631

Cellular automata approach for the dynamics of HIV infection under antiretroviral therapies: The role of the virus diffusion

NASA Astrophysics Data System (ADS)

González, Ramón E. R.; de Figueirêdo, Pedro Hugo; Coutinho, Sérgio

2013-10-01

We study a cellular automata model to test the timing of antiretroviral therapy strategies for the dynamics of infection with human immunodeficiency virus (HIV). We focus on the role of virus diffusion when its population is included in previous cellular automata model that describes the dynamics of the lymphocytes cells population during infection. This inclusion allows us to consider the spread of infection by the virus-cell interaction, beyond that which occurs by cell-cell contagion. The results show an acceleration of the infectious process in the absence of treatment, but show better efficiency in reducing the risk of the onset of AIDS when combined antiretroviral therapies are used even with drugs of low effectiveness. Comparison of results with clinical data supports the conclusions of this study.

An autopsy case of chronic active Epstein-Barr virus infection (CAEBV): distribution of central nervous system (CNS) lesions.

PubMed

Kobayashi, Zen; Tsuchiya, Kuniaki; Takahashi, Makoto; Yokota, Osamu; Sasaki, Atsushi; Bhunchet, Ekapot; Arai, Tetsuaki; Akiyama, Haruhiko; Kamoshita, Masaharu; Kotera, Minoru; Mizusawa, Hidehiro

2008-12-15

A 27-year-old Japanese man developed recurrent respiratory and central nervous system (CNS) symptoms, and hemophagocytic syndromes with a clinical course of 6 years. CT demonstrated multiple nodular lesions in the bilateral lungs, and MRI revealed multiple abnormal intensity areas in the brain and spinal cord. Cerebrospinal fluid (CSF) examination disclosed mild pleocytosis and the presence of Epstein-Barr virus (EBV)-DNA detected by polymerase chain reaction (PCR). The patient died of a hemorrhagic shock associated with a hemophagocytic syndrome. A postmortem study revealed massive hemorrhage in the abdominal cavity and iliopsoas muscles, as well as diffuse infiltration of lymphocytes and/or macrophages into the lungs, liver, kidneys, spleen, cardiac muscle, bone marrow, and CNS. The severe involvement was demonstrated in the CNS, especially in the spinal cord and brainstem. The CD3 positive cells of the brainstem were EBV-encoded RNA 1 positive. This is the first autopsy case of chronic active EBV infection (CAEBV) in which severe and extensive CNS involvement was demonstrated.

No measurable adverse effects of Lassa, Morogoro and Gairo arenaviruses on their rodent reservoir host in natural conditions.

PubMed

Mariën, Joachim; Borremans, Benny; Gryseels, Sophie; Soropogui, Barré; De Bruyn, Luc; Bongo, Gédéon Ngiala; Becker-Ziaja, Beate; de Bellocq, Joëlle Goüy; Günther, Stephan; Magassouba, N'Faly; Leirs, Herwig; Fichet-Calvet, Elisabeth

2017-04-27

In order to optimize net transmission success, parasites are hypothesized to evolve towards causing minimal damage to their reservoir host while obtaining high shedding rates. For many parasite species however this paradigm has not been tested, and conflicting results have been found regarding the effect of arenaviruses on their rodent host species. The rodent Mastomys natalensis is the natural reservoir host of several arenaviruses, including Lassa virus that is known to cause Lassa haemorrhagic fever in humans. Here, we examined the effect of three arenaviruses (Gairo, Morogoro and Lassa virus) on four parameters of wild-caught Mastomys natalensis: body mass, head-body length, sexual maturity and fertility. After correcting for the effect of age, we compared these parameters between arenavirus-positive (arenavirus RNA or antibody) and negative animals using data from different field studies in Guinea (Lassa virus) and Tanzania (Morogoro and Gairo viruses). Although the sample sizes of our studies (1297, 749 and 259 animals respectively) were large enough to statistically detect small differences in body conditions, we did not observe any adverse effects of these viruses on Mastomys natalensis. We did find that sexual maturity was significantly positively related with Lassa virus antibody presence until a certain age, and with Gairo virus antibody presence in general. Gairo virus antibody-positive animals were also significantly heavier and larger than antibody-free animals. Together, these results suggest that the pathogenicity of arenaviruses is not severe in M. natalensis, which is likely to be an adaptation of these viruses to optimize transmission success. They also suggest that sexual behaviour might increase the probability of M. natalensis to become infected with arenaviruses.

Positioning the Undervalued Metropolitan University.

ERIC Educational Resources Information Center

Brown, Herbert E.

1993-01-01

It is noted that "undervalued metropolitan universities," which generally have open enrollment, low tuition, and a large proportion of nontraditional students, often also have a diffuse and unclear public image. A model positioning concept for these institutions, used by Wright State University (Ohio) is proposed and described. (MSE)

A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs

PubMed Central

Wang, Zeng; Yang, Huanliang; Chen, Yan; Tao, Shiyu; Liu, Liling; Kong, Huihui; Ma, Shujie; Meng, Fei; Suzuki, Yasuo; Qiao, Chuanling

2017-01-01

ABSTRACT Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains. IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by increasing virus affinity for human-type receptors. In this study, we explored the genetic basis of the transmissibility difference between two Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses in guinea pigs and found that the amino acid glutamic acid at position 225 in the HA1 protein plays a critical role in the transmission of EAH1N1 virus by increasing the efficiency of viral assembly and budding. PMID:28814518

A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs.

PubMed

Wang, Zeng; Yang, Huanliang; Chen, Yan; Tao, Shiyu; Liu, Liling; Kong, Huihui; Ma, Shujie; Meng, Fei; Suzuki, Yasuo; Qiao, Chuanling; Chen, Hualan

2017-11-01

Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains. IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by increasing virus affinity for human-type receptors. In this study, we explored the genetic basis of the transmissibility difference between two Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses in guinea pigs and found that the amino acid glutamic acid at position 225 in the HA1 protein plays a critical role in the transmission of EAH1N1 virus by increasing the efficiency of viral assembly and budding. Copyright © 2017 Wang et al.

Diphosphates at the 5' end of the positive strand of yeast L-A double-stranded RNA virus as a molecular self-identity tag.

PubMed

Fujimura, Tsutomu; Esteban, Rosa

2016-10-01

The 5'end of RNA conveys important information on self-identity. In mammalian cells, double-stranded RNA (dsRNA) with 5'di- or triphosphates generated during virus infection is recognized as foreign and elicits the host innate immune response. Here, we analyze the 5' ends of the dsRNA genome of the yeast L-A virus. The positive strand has largely diphosphates with a minor amount of triphosphates, while the negative strand has only diphosphates. Although the virus can produce capped transcripts by cap snatching, neither strand carried a cap structure, suggesting that only non-capped transcripts serve as genomic RNA for encapsidation. We also found that the 5' diphosphates of the positive but not the negative strand within the dsRNA genome are crucial for transcription in vitro. Furthermore, the presence of a cap structure in the dsRNA abrogated its template activity. Given that the 5' diphosphates of the transcripts are also essential for cap acquisition and that host cytosolic RNAs (mRNA, rRNA, and tRNA) are uniformly devoid of 5' pp-structures, the L-A virus takes advantage of its 5' terminal diphosphates, using them as a self-identity tag to propagate in the host cytoplasm. © 2016 John Wiley & Sons Ltd.

Evolutionary Analysis of Structural Protein Gene VP1 of Foot-and-Mouth Disease Virus Serotype Asia 1

PubMed Central

Zhang, Qingxun; Liu, Xinsheng; Fang, Yuzhen; Pan, Li; Lv, Jianliang; Zhang, Zhongwang; Zhou, Peng; Ding, Yaozhong; Chen, Haotai; Shao, Junjun; Zhao, Furong; Lin, Tong; Chang, Huiyun; Zhang, Jie; Wang, Yonglu; Zhang, Yongguang

2015-01-01

Foot-and-mouth disease virus (FMDV) serotype Asia 1 was mostly endemic in Asia and then was responsible for economically important viral disease of cloven-hoofed animals, but the study on its selection and evolutionary process is comparatively rare. In this study, we characterized 377 isolates from Asia collected up until 2012, including four vaccine strains. Maximum likelihood analysis suggested that the strains circulating in Asia were classified into 8 different groups (groups I–VIII) or were unclassified (viruses collected before 2000). On the basis of divergence time analyses, we infer that the TMRCA of Asia 1 virus existed approximately 86.29 years ago. The result suggested that the virus had a high mutation rate (5.745 × 10−3 substitutions/site/year) in comparison to the other serotypes of FMDV VP1 gene. Furthermore, the structural protein VP1 was under lower selection pressure and the positive selection occurred at many sites, and four codons (positions 141, 146, 151, and 169) were located in known critical antigenic residues. The remaining sites were not located in known functional regions and were moderately conserved, and the reason for supporting all sites under positive selection remains to be elucidated because the power of these analyses was largely unknown. PMID:25793223

Continental synchronicity of human influenza virus epidemics despite climactic variation

PubMed Central

Sullivan, Sheena; Barr, Ian

2018-01-01

The factors that determine the pattern and rate of spread of influenza virus at a continental-scale are uncertain. Although recent work suggests that influenza epidemics in the United States exhibit a strong geographical correlation, the spatiotemporal dynamics of influenza in Australia, a country and continent of approximately similar size and climate complexity but with a far smaller population, are not known. Using a unique combination of large-scale laboratory-confirmed influenza surveillance comprising >450,000 entries and genomic sequence data we determined the local-level spatial diffusion of this important human pathogen nationwide in Australia. We used laboratory-confirmed influenza data to characterize the spread of influenza virus across Australia during 2007–2016. The onset of established epidemics varied across seasons, with highly synchronized epidemics coinciding with the emergence of antigenically distinct viruses, particularly during the 2009 A/H1N1 pandemic. The onset of epidemics was largely synchronized between the most populous cities, even those separated by distances of >3000 km and those that experience vastly diverse climates. In addition, by analyzing global phylogeographic patterns we show that the synchronized dissemination of influenza across Australian cities involved multiple introductions from the global influenza population, coupled with strong domestic connectivity, rather than through the distinct radial patterns of geographic dispersal that are driven by work-flow transmission as observed in the United States. In addition, by comparing the spatial structure of influenza A and B, we found that these viruses tended to occupy different geographic regions, and peak in different seasons, perhaps indicative of moderate cross-protective immunity or viral interference effects. The highly synchronized outbreaks of influenza virus at a continental-scale revealed here highlight the importance of coordinated public health responses in the event of the emergence of a novel, human-to-human transmissible, virus. PMID:29324895

Epstein-Barr virus-associated peripheral T-Cell lymphoma involving spleen in a renal transplant patient.

PubMed Central

Lee, Hye Kyung; Kim, Hee Jung; Lee, Eun Hee; Kim, Suk Young; Park, Tae In; Kang, Chang Suk; Yang, Woo Ick

2003-01-01

The incidence of posttransplantation lymphoproliferative disorders (PTLDs) has increased in recent years. Although rare, various types of T-cell lymphoma have been reported and their association with Epstein-Barr virus (EBV) has been compared with B-cell PTLDs. We report a case of splenic peripheral T-cell lymphoma occurring in a 47-yr-old male patient 7 yr after renal allograft transplantation. The spleen showed sinusoidal proliferation of focal CD30 positive, large, atypical lymphoid cells. Positivity for CD3 and cytolytic granule-associated proteins was also demonstrated in the tumor cells, while anaplastic large cell lymphoma kinase (ALK) and CD8 were not expressed. Strong nuclear signals for EBV mRNA were noted by EBER1 in situ hybridization. A molecular genetic study demonstrated a rearrangement of the gamma T-cell receptor gene. To our knowledge, this case is unique in terms of a posttransplant T-cell lymphoma that shows focal CD30, cytolytic granule-associated proteins, and EBV positivity. PMID:12692428

A serological survey for avian infectious bronchitis virus and Newcastle disease virus antibodies in backyard (free-range) village chickens in Mexico.

PubMed

Gutierrez-Ruiz, E J; Ramirez-Cruz, G T; Camara Gamboa, E I; Alexander, D J; Gough, R E

2000-12-01

The commercial flocks in Yucatan, Mexico are free of Newcastle disease virus (NDV) in its velogenic viscerotropic form, but little is known about the disease status of backyard poultry. A seroprevalence survey in 30 villages using haemagglutination inhibition (HI) tests for infectious bronchitis virus (IBV) and NDV antibodies was carried out from December 1997 to June 1998. The seroprevalences were 56.5% (95% CI 50-63%) for IBV and 2.2% (95% CI 0.5-3.8%) for NDV. All the villages had chickens that were positive for antibodies to IBV and nine of the villages had chickens that were positive for antibodies to NDV. This suggests that IBV may be responsible for a large proportion of the respiratory disease observed in backyard chickens in Yucatan. The implications of these findings are discussed, including the highly susceptible status of the backyard chickens in Yucatan to NDV and the possibility of this virus being one cause of the syndrome known as mortandad by the local people.

Zika Virus Exposure in an HIV-Infected Cohort in Ghana.

PubMed

Sherman, K E; Rouster, S D; Kong, L X; Shata, T M; Archampong, T; Kwara, A; Aliota, M T; Blackard, J T

2018-04-27

To determine the prevalence and epidemiologic associations of Zika Virus (ZIKV) in HIV-infected patients in Ghana, West Africa. We examined the seroprevalence of ZIKV in HIV/HBV co-infected persons in Ghana from sera samples collected from 2012 to 2014 using ELISA assays and plaque reduction neutralization tests (PRNT). Overall, ZIKV antibody was detected in 12.9% of 236 tested samples, though the true estimate of exposure is probably less due cross-reactions with other related viruses. PRNTs were performed on a subset to provide an estimate of the frequency of false positive reaction. Dengue virus testing was also performed and antibody prevalence was 87.2%. The median CD4 count was 436 (range 2-1781 cell/mm) and did not affect antibody results. Regional geographic ethnicity was associated with ZIKV exposure. Overall, these data suggest that ZIKV infection is a relatively prevalent infection in HIV-positive persons in Ghana though not as common as dengue. Further evaluation of the effect of ZIKV and HIV co-infection is warranted given the large geographical overlap of populations exposed to both viruses.

CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant

ClinicalTrials.gov

2017-02-14

Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia

Mechanisms of boron diffusion in silicon and germanium

NASA Astrophysics Data System (ADS)

Mirabella, S.; De Salvador, D.; Napolitani, E.; Bruno, E.; Priolo, F.

2013-01-01

B migration in Si and Ge matrices raised a vast attention because of its influence on the production of confined, highly p-doped regions, as required by the miniaturization trend. In this scenario, the diffusion of B atoms can take place under severe conditions, often concomitant, such as very large concentration gradients, non-equilibrium point defect density, amorphous-crystalline transition, extrinsic doping level, co-doping, B clusters formation and dissolution, ultra-short high-temperature annealing. In this paper, we review a large amount of experimental work and present our current understanding of the B diffusion mechanism, disentangling concomitant effects and describing the underlying physics. Whatever the matrix, B migration in amorphous (α-) or crystalline (c-) Si, or c-Ge is revealed to be an indirect process, activated by point defects of the hosting medium. In α-Si in the 450-650 °C range, B diffusivity is 5 orders of magnitude higher than in c-Si, with a transient longer than the typical amorphous relaxation time. A quick B precipitation is also evidenced for concentrations larger than 2 × 1020 B/cm3. B migration in α-Si occurs with the creation of a metastable mobile B, jumping between adjacent sites, stimulated by dangling bonds of α-Si whose density is enhanced by B itself (larger B density causes higher B diffusivity). Similar activation energies for migration of B atoms (3.0 eV) and of dangling bonds (2.6 eV) have been extracted. In c-Si, B diffusion is largely affected by the Fermi level position, occurring through the interaction between the negatively charged substitutional B and a self-interstitial (I) in the neutral or doubly positively charged state, if under intrinsic or extrinsic (p-type doping) conditions, respectively. After charge exchanges, the migrating, uncharged BI pair is formed. Under high n-type doping conditions, B diffusion occurs also through the negatively charged BI pair, even if the migration is depressed by Coulomb pairing with n-type dopants. The interplay between B clustering and migration is also modeled, since B diffusion is greatly affected by precipitation. Small (below 1 nm) and relatively large (5-10 nm in size) BI clusters have been identified with different energy barriers for thermal dissolution (3.6 or 4.8 eV, respectively). In c-Ge, B motion is by far less evident than in c-Si, even if the migration mechanism is revealed to be similarly assisted by Is. If Is density is increased well above the equilibrium (as during ion irradiation), B diffusion occurs up to quite large extents and also at relatively low temperatures, disclosing the underlying mechanism. The lower B diffusivity and the larger activation barrier (4.65 eV, rather than 3.45 eV in c-Si) can be explained by the intrinsic shortage of Is in Ge and by their large formation energy. B diffusion can be strongly enhanced with a proper point defect engineering, as achieved with embedded GeO2 nanoclusters, causing at 650 °C a large Is supersaturation. These aspects of B diffusion are presented and discussed, modeling the key role of point defects in the two different matrices.

The Role of Faith-Based Organizations in the Education, Support, and Services for Persons Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome.

PubMed

Stephens, Teresa M

2018-03-01

Faith-based organizations are in a unique position to provide resilience-enhancing efforts for persons living with human immunodeficiency virus/AIDS. Many persons living with human immunodeficiency virus/AIDS report having a strong faith or religious affiliation, with a large percentage attending church services on a regular basis. Faith-based organizations can use these factors to reach out to these individuals and effectively promote health, well-being, education, and support. Faith-based organizations can contribute to the reduction of stigma and isolation for persons living with human immunodeficiency virus/AIDS. Copyright © 2017 Elsevier Inc. All rights reserved.

Highly divergent cyclo-like virus in a great roundleaf bat (Hipposideros armiger) in Vietnam.

PubMed

Kemenesi, Gábor; Kurucz, Kornélia; Zana, Brigitta; Tu, Vuong Tan; Görföl, Tamás; Estók, Péter; Földes, Fanni; Sztancsik, Katalin; Urbán, Péter; Fehér, Enikő; Jakab, Ferenc

2017-08-01

Members of the viral family Circoviridae are increasingly recognized worldwide. Bats seem to be natural reservoirs or dietary-related dispensers of these viruses. Here, we report a distantly related member of the genus Cyclovirus detected in the faeces of a great roundleaf bat (Hipposideros armiger). Interestingly, the novel virus lacks a Circoviridae-specific stem-loop structure, although a Geminiviridae-like nonamer sequence was detected in the large intergenic region. Based on these differences and its phylogenetic position, we propose that our new virus represents a distant and highly divergent member of the genus Cyclovirus. However it is lacking several characteristics of members of the genus, which raises a challenge in its taxonomic classification.

Competitive Fitness of Influenza B Viruses Possessing E119A and H274Y Neuraminidase Inhibitor Resistance-Associated Substitutions in Ferrets.

PubMed

Pascua, Philippe Noriel Q; Marathe, Bindumadhav M; Burnham, Andrew J; Vogel, Peter; Webby, Richard J; Webster, Robert G; Govorkova, Elena A

2016-01-01

Neuraminidase (NA) inhibitors (NAIs) are the only antiviral drugs recommended for influenza treatment and prophylaxis. Although NAI-resistant influenza B viruses that could pose a threat to public health have been reported in the field, their fitness is poorly understood. We evaluated in ferrets the pathogenicity and relative fitness of reverse genetics (rg)-generated influenza B/Yamanashi/166/1998-like viruses containing E119A or H274Y NA substitutions (N2 numbering). Ferrets inoculated with NAI-susceptible rg-wild-type (rg-WT) or NAI-resistant (rg-E119A or rg-H274Y) viruses developed mild infections. Growth of rg-E119A virus in the nasal cavities was delayed, but the high titers at 3 days post-inoculation (dpi) were comparable to those of the rg-WT and rg-H274Y viruses (3.6-4.1 log10TCID50/mL). No virus persisted beyond 5 dpi and replication did not extend to the trachea or lungs. Positive virus antigen-staining of the nasal turbinate epithelium was intermittent with the rg-WT and rg-H274Y viruses; whereas antigen-staining for the rg-E119A virus was more diffuse. Virus populations in ferrets coinoculated with NAI-susceptible and -resistant viruses (1:1 mixture) remained heterogeneous at 5 dpi but were predominantly rg-WT (>70%). Although the E119A substitution was associated with delayed replication in ferrets, the H274Y substitution did not measurably affect viral growth properties. These data suggest that rg-H274Y has undiminished fitness in single virus inoculations, but neither rg-E119A nor rg-H274Y gained a fitness advantage over rg-WT in direct competition experiments without antiviral drug pressure. Taken together, our data suggest the following order of relative fitness in a ferret animal model: rg-WT > rg-H274Y > rg-E119A.

Competitive Fitness of Influenza B Viruses Possessing E119A and H274Y Neuraminidase Inhibitor Resistance–Associated Substitutions in Ferrets

PubMed Central

Pascua, Philippe Noriel Q.; Marathe, Bindumadhav M.; Burnham, Andrew J.; Vogel, Peter; Webby, Richard J.; Webster, Robert G.; Govorkova, Elena A.

2016-01-01

Neuraminidase (NA) inhibitors (NAIs) are the only antiviral drugs recommended for influenza treatment and prophylaxis. Although NAI-resistant influenza B viruses that could pose a threat to public health have been reported in the field, their fitness is poorly understood. We evaluated in ferrets the pathogenicity and relative fitness of reverse genetics (rg)–generated influenza B/Yamanashi/166/1998-like viruses containing E119A or H274Y NA substitutions (N2 numbering). Ferrets inoculated with NAI-susceptible rg–wild-type (rg-WT) or NAI-resistant (rg-E119A or rg-H274Y) viruses developed mild infections. Growth of rg-E119A virus in the nasal cavities was delayed, but the high titers at 3 days post-inoculation (dpi) were comparable to those of the rg-WT and rg-H274Y viruses (3.6–4.1 log10TCID50/mL). No virus persisted beyond 5 dpi and replication did not extend to the trachea or lungs. Positive virus antigen-staining of the nasal turbinate epithelium was intermittent with the rg-WT and rg-H274Y viruses; whereas antigen-staining for the rg-E119A virus was more diffuse. Virus populations in ferrets coinoculated with NAI-susceptible and -resistant viruses (1:1 mixture) remained heterogeneous at 5 dpi but were predominantly rg-WT (>70%). Although the E119A substitution was associated with delayed replication in ferrets, the H274Y substitution did not measurably affect viral growth properties. These data suggest that rg-H274Y has undiminished fitness in single virus inoculations, but neither rg-E119A nor rg-H274Y gained a fitness advantage over rg-WT in direct competition experiments without antiviral drug pressure. Taken together, our data suggest the following order of relative fitness in a ferret animal model: rg-WT > rg-H274Y > rg-E119A. PMID:27466813

A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas

ClinicalTrials.gov

2018-04-11

CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Transformed Indolent Non-Hodgkin Lymphoma

Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas

ClinicalTrials.gov

2018-05-02

High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; MYC Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

Primary Intra-aortic Epstein-Barr Virus-Positive Large B-Cell Lymphoma Presenting as Aortic Mural Thrombosis: An Entity Distinct From Intravascular Large B-Cell Lymphoma.

PubMed

Nakao, Ryuta; Sakashita, Aki; Omoto, Atsushi; Sato, Osamu; Hino, Yoko; Yanagisawa, Akio; Urata, Yoji

2017-12-01

Intravascular selective growth of neoplastic B lymphocytes is a characteristic finding of intravascular large B-cell lymphoma (IVLBCL). However, because neoplastic B cells of IVLBCL grow merely in the lumina of capillaries or small vessels, primary IVLBCL of the great vessels is considered exceptional. To our knowledge, only 2 primary B-cell lymphomas in the lumina of the vena cava have been reported. However, there has been no report of primary B-cell lymphoma with intra-aortic growth. We describe a novel manifestation of primary Epstein-Barr virus-positive large B-cell lymphoma mainly affecting the lumina of the aorta and its major branches in a 76-year-old man. He had a long-term fever that was refractory to antibiotics and aortic mural thrombosis with visceral embolization. Because he had no detectable mass suggesting a malignancy, it was difficult to diagnose while he was alive. He died without anticancer treatment, and the confirmed diagnosis was made at autopsy.

Identification of swine influenza A virus and Stenotrophomonas maltophilia co-infection in Chinese pigs.

PubMed

Hou, Dongjun; Bi, Yuhai; Sun, Honglei; Yang, Jun; Fu, Guanghua; Sun, Yipeng; Liu, Jinhua; Pu, Juan

2012-08-22

Influenza virus virulence can be exacerbated by bacterial co-infections. Swine influenza virus (SIV) infection together with some bacteria is found to enhance pathogenicity. SIV-positive samples suspected of containing bacteria were used for bacterial isolation and identification. Antimicrobial susceptibility testing was performed by disc diffusion methods. To investigate the interaction of SIV and the bacteria in vitro, guinea pigs were used as mammalian hosts to determine the effect on viral susceptibility and transmissibility. Differences in viral titers between groups were compared using Student's t-test. During surveillance for SIV in China from 2006 to 2009, seven isolates (24.14%) of 29 influenza A viruses were co-isolated with Stenotrophomonas maltophilia from nasal and tracheal swab samples of pigs. Antimicrobial susceptibility testing showed that the bacteria possessed a high level of resistance towards clinically used antibiotics. To investigate the interaction between these two microorganisms in influencing viral susceptibility and transmission in humans, guinea pigs were used as an infection model. Animals were inoculated with SIV or S. maltophilia alone or co-infected with SIV and S. maltophilia. The results showed that although no transmission among guinea pigs was observed, virus-bacteria co-infections resulted in higher virus titers in nasal washes and trachea and a longer virus shedding period. This is the first report of influenza virus co-infection with S. maltophilia in the Chinese swine population. Increased replication of virus by co-infection with multidrug resistant bacteria might increase the infection rate of SIV in humans. The control of S. maltophilia in clinics will contribute to reducing the spread of SIV in pigs and humans.

Lassa virus infection in experimentally infected marmosets: liver pathology and immunophenotypic alterations in target tissues.

PubMed

Carrion, Ricardo; Brasky, Kathleen; Mansfield, Keith; Johnson, Curtis; Gonzales, Monica; Ticer, Anysha; Lukashevich, Igor; Tardif, Suzette; Patterson, Jean

2007-06-01

Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.

High Incidence of Chikungunya Virus and Frequency of Viremic Blood Donations during Epidemic, Puerto Rico, USA, 2014

PubMed Central

Brès, Vanessa; Lu, Kai; Liss, Nathan M.; Brambilla, Donald J.; Ryff, Kyle R.; Bruhn, Roberta; Velez, Edwin; Ocampo, Derrek; Linnen, Jeffrey M.; Latoni, Gerardo; Petersen, Lyle R.; Williamson, Phillip C.; Busch, Michael P.

2016-01-01

Chikungunya virus (CHIKV) caused large epidemics throughout the Caribbean in 2014. We conducted nucleic acid amplification testing (NAAT) for CHIKV RNA (n = 29,695) and serologic testing for IgG against CHIKV (n = 1,232) in archived blood donor samples collected during and after an epidemic in Puerto Rico in 2014. NAAT yields peaked in October with 2.1% of donations positive for CHIKV RNA. A total of 14% of NAAT-reactive donations posed a high risk for virus transmission by transfusion because of high virus RNA copy numbers (104–109 RNA copies/mL) and a lack of specific IgM and IgG responses. Testing of minipools of 16 donations would not have detected 62.5% of RNA-positive donations detectable by individual donor testing, including individual donations without IgM and IgG. Serosurveys before and after the epidemic demonstrated that nearly 25% of blood donors in Puerto Rico acquired CHIKV infections and seroconverted during the epidemic. PMID:27070192

High Incidence of Chikungunya Virus and Frequency of Viremic Blood Donations during Epidemic, Puerto Rico, USA, 2014.

PubMed

Simmons, Graham; Brès, Vanessa; Lu, Kai; Liss, Nathan M; Brambilla, Donald J; Ryff, Kyle R; Bruhn, Roberta; Velez, Edwin; Ocampo, Derrek; Linnen, Jeffrey M; Latoni, Gerardo; Petersen, Lyle R; Williamson, Phillip C; Busch, Michael P

2016-07-01

Chikungunya virus (CHIKV) caused large epidemics throughout the Caribbean in 2014. We conducted nucleic acid amplification testing (NAAT) for CHIKV RNA (n = 29,695) and serologic testing for IgG against CHIKV (n = 1,232) in archived blood donor samples collected during and after an epidemic in Puerto Rico in 2014. NAAT yields peaked in October with 2.1% of donations positive for CHIKV RNA. A total of 14% of NAAT-reactive donations posed a high risk for virus transmission by transfusion because of high virus RNA copy numbers (10 (4) -10 (9) RNA copies/mL) and a lack of specific IgM and IgG responses. Testing of minipools of 16 donations would not have detected 62.5% of RNA-positive donations detectable by individual donor testing, including individual donations without IgM and IgG. Serosurveys before and after the epidemic demonstrated that nearly 25% of blood donors in Puerto Rico acquired CHIKV infections and seroconverted during the epidemic.

Probe diffusion of labeled polymers inside polyacrylic acid solutions: A polyelectrolyte effect

NASA Astrophysics Data System (ADS)

Mishra, Banani; Mithra, K.; Khandai, Santripti; Jena, Sidhartha S.

2018-05-01

Probe diffusion of fluorescently labeled Dextran 40 inside polyelectrolyte solution of polyacrylic acid (PAA) was investigated using Fluorescence Recovery After Photobleaching technique. The crowding and interaction effects on probe diffusion were controlled by tuning background polymer and added external electrolyte concentration. For all the salt concentration, an overall decrease in diffusion coefficient is observed with rise in polymer concentration. The diffusion coefficient decreases with decrease in salt concentration whereas the solution viscosity increases, indicating a competition between viscous drag and electrostatic interaction. A large positive deviation from the ideal Stokes-Einstein relation is observed for high polymer and low salt concentration, which reduces markedly with addition of salt confirming polyelectrolyte effects, plays a major role in deciding the probe diffusion.

Endoscopic appearance of AIDS-related gastrointestinal lymphoma with c-MYC rearrangements: case report and literature review.

PubMed

Tanaka, Shohei; Nagata, Naoyoshi; Mine, Sohtaro; Igari, Toru; Kobayashi, Taiichiro; Sugihara, Jun; Honda, Haruhito; Teruya, Katsuji; Kikuchi, Yoshimi; Oka, Shinichi; Uemura, Naomi

2013-08-07

Acquired immune deficiency syndrome (AIDS)-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the highly active anti-retroviral therapy (HAART) era. Recently, rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma. Here, we report a rare case of gastrointestinal (GI)-ARL with MYC rearrangements and coinfected with Epstein-Barr virus (EBV) infection presenting with various endoscopic findings. A 38-year-old homosexual man who presented with anemia and was diagnosed with an human immunodeficiency virus infection for the first time. GI endoscopy revealed multiple dish-like lesions, ulcerations, bloody spots, nodular masses with active bleeding in the stomach, erythematous flat lesions in the duodenum, and multiple nodular masses in the colon and rectum. Magnified endoscopy with narrow band imaging showed a honeycomb-like pattern without irregular microvessels in the dish-like lesions of the stomach. Biopsy specimens from the stomach, duodenum, colon, and rectum revealed diffuse large B-cell lymphoma concomitant with EBV infection that was detected by high tissue EBV-polymerase chain reaction levels and Epstein-Barr virus small RNAs in situ hybridization. Fluorescence in situ hybridization analysis revealed a fusion between the immunoglobulin heavy chain (IgH) and c-MYC genes, but not between the IgH and BCL2 loci. After 1-mo of treatment with HAART and R-CHOP, endoscopic appearance improved remarkably, and the histological features of the biopsy specimens revealed no evidence of lymphoma. However, he died from multiple organ failure on the 139(th) day after diagnosis. The cause of his poor outcome may be related to MYC rearrangement. The GI tract involvement in ARL is rarely reported, and its endoscopic findings are various and may be different from those in non-AIDS GI lymphoma; thus, we also conducted a literature review of GI-ARL cases.

Endoscopic appearance of AIDS-related gastrointestinal lymphoma with c-MYC rearrangements: Case report and literature review

PubMed Central

Tanaka, Shohei; Nagata, Naoyoshi; Mine, Sohtaro; Igari, Toru; Kobayashi, Taiichiro; Sugihara, Jun; Honda, Haruhito; Teruya, Katsuji; Kikuchi, Yoshimi; Oka, Shinichi; Uemura, Naomi

2013-01-01

Acquired immune deficiency syndrome (AIDS)-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the highly active anti-retroviral therapy (HAART) era. Recently, rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma. Here, we report a rare case of gastrointestinal (GI)-ARL with MYC rearrangements and coinfected with Epstein-Barr virus (EBV) infection presenting with various endoscopic findings. A 38-year-old homosexual man who presented with anemia and was diagnosed with an human immunodeficiency virus infection for the first time. GI endoscopy revealed multiple dish-like lesions, ulcerations, bloody spots, nodular masses with active bleeding in the stomach, erythematous flat lesions in the duodenum, and multiple nodular masses in the colon and rectum. Magnified endoscopy with narrow band imaging showed a honeycomb-like pattern without irregular microvessels in the dish-like lesions of the stomach. Biopsy specimens from the stomach, duodenum, colon, and rectum revealed diffuse large B-cell lymphoma concomitant with EBV infection that was detected by high tissue EBV-polymerase chain reaction levels and Epstein-Barr virus small RNAs in situ hybridization. Fluorescence in situ hybridization analysis revealed a fusion between the immunoglobulin heavy chain (IgH) and c-MYC genes, but not between the IgH and BCL2 loci. After 1-mo of treatment with HAART and R-CHOP, endoscopic appearance improved remarkably, and the histological features of the biopsy specimens revealed no evidence of lymphoma. However, he died from multiple organ failure on the 139th day after diagnosis. The cause of his poor outcome may be related to MYC rearrangement. The GI tract involvement in ARL is rarely reported, and its endoscopic findings are various and may be different from those in non-AIDS GI lymphoma; thus, we also conducted a literature review of GI-ARL cases. PMID:23922484

Antibody to the rheumatoid arthritis nuclear antigen. Its relationship to in vivo Epstein-Barr virus infection.

PubMed

Catalano, M A; Carson, D A; Niederman, J C; Feorino, P; Vaughan, J H

1980-05-01

Most patients with seropositive rheumatoid arthritis, and a variable but lesser percentage of normal subjects, have precipitating antibodies to a nuclear antigen, rheumatoid arthritis nuclear antigen, present in Epstein-Barr virus-infected human B lymphoblastoid cells. We have used a sensitive indirect immunofluorescence assay for antibody to rheumatoid arthritis nuclear antigen in a study of patients with infectious mononucleosis and healthy control subjects. Of 110 sera from normal, college-age cadets, 58 were from individuals without prior Epstein-Barr virus infection, as indicated by the lack of antibody to viral capsid antigen. All of these also lacked activity to rheumatoid arthritis nuclear antigen. 52 sera were positive for antibody to viral capsid antigen, and antibody to rheumatoid arthritis nuclear antigen was present in 26 (50%) of these. In 67 sequential sera from 11 college-age students with infectious mononucleosis who became positive for antibody to rheumatoid arthritis nuclear antigen, only 2 were positive during the 1 mo. Thereafter the incidence and titers increased progressively through the 1st yr after infection. This time-course resembled that for the development of antibody to Epstein-Barr nuclear antigen, another transformation antigen in Epstein-Barr virus-infected B lymphocytes. The development of positivity for both was much later than that of antibody to the structural viral capsid antigen, which in the current study was always positive by 1 wk. Thus, antibody to rheumatoid arthritis nuclear antigen is present in a large proportion of normal individuals and can now be clearly ascribed, from both in vivo and in vitro studies, to prior infection with Epstein-Barr virus.

Driven Microbead Rheology of Fibrin Gels

NASA Astrophysics Data System (ADS)

Spero, R. C.; Smith, B.; Cribb, J.; O'Brien, T. E.; Lord, S. T.; Superfine, R.

2006-11-01

The rheological properties of fibrin, the primary structural element in blood clots, have been widely studied at the macroscopic level, because its mechanical properties are critical to its physiological function. Microbead rheology (MBR) shows promise for advancing this field in various ways. First, MBR can be performed on small sample quantities (˜1 uL), which is useful for high-throughput experimentation; second, fibrin's complex structure has a range of length scales, such that large cells may not propagate while small viruses diffuse easily through the mesh. Microbeads from 10 um to under 500 nm can probe these length scales. These characteristics suggest MBR could be useful in screening drugs for disorders involving variant clot rigidity. We report on efforts to measure the rheology of fibrin gels over the course of its polymerization. A magnetic force microscope applies pulsed forces to microbeads suspended in fibrin gels. Beads are monitored on an inverted microscope and their positions tracked by software over the 30-minute course of the gelation. A single mode Jefferies model is used to extract viscosity and elasticity from the beads' creep-recovery.

Detection of Influenza A viruses at migratory bird stopover sites in Michigan, USA.

PubMed

Lickfett, Todd M; Clark, Erica; Gehring, Thomas M; Alm, Elizabeth W

2018-01-01

Introduction: Influenza A viruses have the potential to cause devastating illness in humans and domestic poultry. Wild birds are the natural reservoirs of Influenza A viruses and migratory birds are implicated in their global dissemination. High concentrations of this virus are excreted in the faeces of infected birds and faecal contamination of shared aquatic habitats can lead to indirect transmission among birds via the faecal-oral route. The role of migratory birds in the spread of avian influenza has led to large-scale surveillance efforts of circulating avian influenza viruses through direct sampling of live and dead wild birds. Environmental monitoring of bird habitats using molecular detection methods may provide additional information on the persistence of influenza virus at migratory stopover sites distributed across large spatial scales. Materials and methods: In the current study, faecal and water samples were collected at migratory stopover sites and evaluated for Influenza A by real-time quantitative reverse transcriptase PCR. Results and Discussion: This study found that Influenza A was detected at 53% of the evaluated stopover sites, and 7% and 4.8% of the faecal and water samples, respectively, tested positive for Influenza A virus. Conclusion: Environmental monitoring detected Influenza A at stopover sites used by migratory birds.

Directional Spread of Surface-Associated Retroviruses Regulated by Differential Virus-Cell Interactions▿ †

PubMed Central

Sherer, Nathan M.; Jin, Jing; Mothes, Walther

2010-01-01

The spread of viral infections involves the directional progression of virus particles from infected cells to uninfected target cells. Prior to entry, the binding of virus particles to specific cell surface receptors can trigger virus surfing, an actin-dependent lateral transport of viruses toward the cell body (M. J. Lehmann et al., J. Cell Biol. 170:317-325, 2005; M. Schelhaas, et al., PLoS Pathog. 4:e1000148, 2008; J. L. Smith, D. S. Lidke, and M. A. Ozbun, Virology 381:16-21, 2008). Here, we have used live-cell imaging to demonstrate that for cells chronically infected with the gammaretrovirus murine leukemia virus in which receptor has been downregulated, a significant portion of completely assembled virus particles are not immediately released into the supernatant but retain long-term association with the cell surface. Retention can be attributed, at least in part, to nonspecific particle attachment to cell surface glycosylaminoglycans. In contrast to virus surfing, viruses retained at the surface of infected cells undergo a lateral motility that is random and actin independent. This diffusive motility can be abruptly halted and converted into inward surfing after treatment with Polybrene, a soluble cation that increases virus-cell adsorption. In the absence of Polybrene, particle diffusion allows for an outward flow of viruses to the infected cell periphery. Peripheral particles are readily captured by and transmitted to neighboring uninfected target cells in a directional fashion. These data demonstrate a surface-based mechanism for the directional spread of viruses regulated by differential virus-cell interactions. PMID:20089647

Pathogenesis of occult chronic hepatitis B virus infection

PubMed Central

de la Fuente, Rocio Aller; Gutiérrez, María L; Garcia-Samaniego, Javier; Fernández-Rodriguez, Conrado; Lledó, Jose Luis; Castellano, Gregorio

2011-01-01

Occult hepatitis B infection (OBI) is characterized by hepatitis B virus (HBV) DNA in serum in the absence of hepatitis B surface antigen (HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns. Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays; but more frequently it is due to a strong suppression of viral replication and gene expression. OBI is an entity with world-wide diffusion. The failure to detect HBsAg, despite the persistence of the viral DNA, is due in most cases to the strong suppression of viral replication and gene expression that characterizes this “occult” HBV infection; although the mechanisms responsible for suppression of HBV are not well understood. The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection. Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma. PMID:21472118

Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA.

PubMed Central

Prats, A C; Sarih, L; Gabus, C; Litvak, S; Keith, G; Darlix, J L

1988-01-01

Retrovirus virions carry a diploid genome associated with a large number of small viral finger protein molecules which are required for encapsidation. Our present results show that finger protein p12 of Rous sarcoma virus (RSV) and p10 of murine leukaemia virus (MuLV) positions replication primer tRNA on the replication initiation site (PBS) at the 5' end of the RNA genome. An RSV mutant with a Val-Pro insertion in the finger motif of p12 is able to partially encapsidate genomic RNA but is not infectious because mutated p12 is incapable of positioning the replication primer, tRNATrp. Since all known replication competent retroviruses, and the plant virus CaMV, code for finger proteins analogous to RSV p12 or MuLV p10, the initial stage of reverse transcription in avian, mammalian and human retroviruses and in CaMV is probably controlled in an analogous way. Images PMID:2458920

Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA.

PubMed

Prats, A C; Sarih, L; Gabus, C; Litvak, S; Keith, G; Darlix, J L

1988-06-01

Retrovirus virions carry a diploid genome associated with a large number of small viral finger protein molecules which are required for encapsidation. Our present results show that finger protein p12 of Rous sarcoma virus (RSV) and p10 of murine leukaemia virus (MuLV) positions replication primer tRNA on the replication initiation site (PBS) at the 5' end of the RNA genome. An RSV mutant with a Val-Pro insertion in the finger motif of p12 is able to partially encapsidate genomic RNA but is not infectious because mutated p12 is incapable of positioning the replication primer, tRNATrp. Since all known replication competent retroviruses, and the plant virus CaMV, code for finger proteins analogous to RSV p12 or MuLV p10, the initial stage of reverse transcription in avian, mammalian and human retroviruses and in CaMV is probably controlled in an analogous way.

Glutathione peroxidase 4 overexpression inhibits ROS-induced cell death in diffuse large B-cell lymphoma.

PubMed

Kinowaki, Yuko; Kurata, Morito; Ishibashi, Sachiko; Ikeda, Masumi; Tatsuzawa, Anna; Yamamoto, Masahide; Miura, Osamu; Kitagawa, Masanobu; Yamamoto, Kouhei

2018-02-20

Regulation of oxidative stress and redox systems has important roles in carcinogenesis and cancer progression, and for this reason has attracted much attention as a new area of cancer therapeutic targets. Glutathione peroxidase 4 (GPX4), an antioxidant enzyme, has biological important functions such as signaling cell death by suppressing peroxidation of membrane phospholipids. However, few studies exist on the expression and clinical relevance of GPX4 in malignant lymphomas such as diffuse large B-cell lymphoma. In this study, we assessed the expression of GPX4 immunohistochemically. GPX4 was expressed in 35.5% (33/93) cases of diffuse large B-cell lymphoma. The GPX4-positive group had poor overall survival (P = 0.0032) and progression-free survival (P = 0.0004) compared with those of the GPX4-negative group. In a combined analysis of GPX4 and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, there was a negative correlation between GPX4 and 8-hydroxydeoxyguanosine (P = 0.0009). The GPX4-positive and 8-hydroxydeoxyguanosine-negative groups had a significantly worse prognosis than the other groups in both overall survival (P = 0.0170) and progression-free survival (P = 0.0005). These results suggest that the overexpression of GPX4 is an independent prognostic predictor in diffuse large B-cell lymphoma. Furthermore, in vitro analysis demonstrated that GPX4-overexpressing cells were resistant to reactive oxygen species-induced cell death (P = 0.0360). Conversely, GPX4-knockdown cells were sensitive to reactive oxygen species-induced cell death (P = 0.0111). From these data, we conclude that GPX4 regulates reactive oxygen species-induced cell death. Our results suggest a novel therapeutic strategy using the mechanism of ferroptosis, as well as a novel prognostic predictor of diffuse large B-cell lymphoma.

Diffusion of influenza viruses among migratory birds with a focus on the Southwest United States.

PubMed

Scotch, Matthew; Lam, Tommy Tsan-Yuk; Pabilonia, Kristy L; Anderson, Theodore; Baroch, John; Kohler, Dennis; DeLiberto, Thomas J

2014-08-01

The Southwest United States, including Arizona and New Mexico, has a diverse climate and is home to many different avian species. We sequenced the hemagglutinin (HA) gene of twenty influenza specimens for the years 2007-2009. This included four from Arizona, and sixteen from New Mexico. We analyzed the sequences and determined the following HA subtypes: H3, H4, H6, H8, and H11. For each subtype, we combined our virus sequences with those from a public database, and inferred phylogeographic models of influenza diffusion. Statistical phylogeography indicated that overall evolutionary diffusion of avian influenza viruses is geographically structured (p<0.05). In addition, we found that diffusion to the Southwest was often from nearby states including California. For H3, H4 and H6, the intra-flyway gene flow rates were significantly (p<0.001) higher than those of inter-flyway. Such rate difference was also observed in H8 and H11, yet, without statistical significance (p=0.132, p=0.190, respectively). Excluding any one flyway from the calculation generated similar results, suggesting that such barrier effect on gene flow rates is not exclusively produced by any single flyway. We also calculated the Bayes factor test for the significant non-zero rates between states and identified significant routes both within and across flyways. Such inter-flyway spread of influenza was probably the result of birds from four flyways co-mingling on breeding grounds in northern regions or marshaling on staging areas post breeding in Canada or Alaska, before moving south each fall. This study provides an initial analysis of evolutionary diffusion of avian influenza virus to and from the Southwest United States. However, more sequences from this region need to be generated to determine the role of host migration and other factors on influenza diffusion. Copyright © 2014 Elsevier B.V. All rights reserved.

A new laboratory-based surveillance system (Respiratory DataMart System) for influenza and other respiratory viruses in England: results and experience from 2009 to 2012.

PubMed

Zhao, H; Green, H; Lackenby, A; Donati, M; Ellis, J; Thompson, C; Bermingham, A; Field, J; Sebastianpillai, P; Zambon, M; Watson, Jm; Pebody, R

2014-01-23

During the 2009 influenza A(H1N1) pandemic, a new laboratory-based virological sentinel surveillance system, the Respiratory DataMart System (RDMS), was established in a network of 14 Health Protection Agency (now Public Health England (PHE)) and National Health Service (NHS) laboratories in England. Laboratory results (both positive and negative) were systematically collected from all routinely tested clinical respiratory samples for a range of respiratory viruses including influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus, adenovirus and human metapneumovirus (hMPV). The RDMS also monitored the occurrence of antiviral resistance of influenza viruses. Data from the RDMS for the 2009–2012 period showed that the 2009 pandemic influenza virus caused three waves of activity with different intensities during the pandemic and post pandemic periods. Peaks in influenza A(H1N1)pdm09 positivity (defined as number of positive samples per total number of samples tested) were seen in summer and autumn in 2009, with slightly higher peak positivity observed in the first post-pandemic season in 2010/2011. The influenza A(H1N1)pdm09 virus strain almost completely disappeared in the second postpandemic season in 2011/2012. The RDMS findings are consistent with other existing community-based virological and clinical surveillance systems. With a large sample size, this new system provides a robust supplementary mechanism, through the collection of routinely available laboratory data at minimum extra cost, to monitor influenza as well as other respiratory virus activity. A near real-time, daily reporting mechanism in the RDMS was established during the London 2012 Olympic and Paralympic Games. Furthermore, this system can be quickly adapted and used to monitor future influenza pandemics and other major outbreaks of respiratory infectious disease, including novel pathogens.

A cross-sectional study to quantify the prevalence of avian influenza viruses in poultry at intervention and non-intervention live bird markets in central Vietnam, 2014.

PubMed

Chu, D-H; Stevenson, M A; Nguyen, L V; Isoda, N; Firestone, S M; Nguyen, T N; Nguyen, L T; Matsuno, K; Okamatsu, M; Kida, H; Sakoda, Y

2017-12-01

In Vietnam, live bird markets are found in most populated centres, providing the means by which fresh poultry can be purchased by consumers for immediate consumption. Live bird markets are aggregation points for large numbers of poultry, and therefore, it is common for a range of avian influenza viruses to be mixed within live bird markets as a result of different poultry types and species being brought together from different geographical locations. We conducted a cross-sectional study in seven live bird markets in four districts of Thua Thien Hue Province in August and December, 2014. The aims of this study were to (i) document the prevalence of avian influenza in live bird markets (as measured by virus isolation); and (ii) quantify individual bird-, seller- and market-level characteristics that rendered poultry more likely to be positive for avian influenza virus at the time of sale. A questionnaire soliciting details of knowledge, attitude and avian influenza practices was administered to poultry sellers in study markets. At the same time, swabs and faecal samples were collected from individual poultry and submitted for isolation of avian influenza virus. The final data set comprised samples from 1,629 birds from 83 sellers in the seven live bird markets. A total of 113 birds were positive for virus isolation; a prevalence of 6.9 (95% CI 5.8-8.3) avian influenza virus-positive birds per 100 birds submitted for sale. After adjusting for clustering at the market and individual seller levels, none of the explanatory variables solicited in the questionnaire were significantly associated with avian influenza virus isolation positivity. The proportions of variance at the individual market, seller and individual bird levels were 6%, 48% and 46%, respectively. We conclude that the emphasis of avian influenza control efforts in Vietnam should be at the individual seller level as opposed to the market level. © 2017 Blackwell Verlag GmbH.

The Impact of Hierarchical Positions on Communities of Learning

ERIC Educational Resources Information Center

Rehm, Martin; Gijselaers, Wim; Segers, Mien

2015-01-01

"Communities of Learning" (CoL) are an innovative methodological tool to stimulate knowledge creation and diffusion within organizations. However, past research has largely overlooked how participants' hierarchical positions influence their behavior within CoL. We address this shortcoming and provide empirical evidence on 25 CoL for a…

Dominance of highly divergent feline leukemia virus A progeny variants in a cat with recurrent viremia and fatal lymphoma.

PubMed

Helfer-Hungerbuehler, A Katrin; Cattori, Valentino; Boretti, Felicitas S; Ossent, Pete; Grest, Paula; Reinacher, Manfred; Henrich, Manfred; Bauer, Eva; Bauer-Pham, Kim; Niederer, Eva; Holznagel, Edgar; Lutz, Hans; Hofmann-Lehmann, Regina

2010-02-19

In a cat that had ostensibly recovered from feline leukemia virus (FeLV) infection, we observed the reappearance of the virus and the development of fatal lymphoma 8.5 years after the initial experimental exposure to FeLV-A/Glasgow-1. The goals of the present study were to investigate this FeLV reoccurrence and molecularly characterize the progeny viruses. The FeLV reoccurrence was detected by the presence of FeLV antigen and RNA in the blood and saliva. The cat was feline immunodeficiency virus positive and showed CD4+ T-cell depletion, severe leukopenia, anemia and a multicentric monoclonal B-cell lymphoma. FeLV-A, but not -B or -C, was detectable. Sequencing of the envelope gene revealed three FeLV variants that were highly divergent from the virus that was originally inoculated (89-91% identity to FeLV-A/Glasgow-1). In the long terminal repeat 31 point mutations, some previously described in cats with lymphomas, were detected. The FeLV variant tissue provirus and viral RNA loads were significantly higher than the FeLV-A/Glasgow-1 loads. Moreover, the variant loads were significantly higher in lymphoma positive compared to lymphoma negative tissues. An increase in the variant provirus blood load was observed at the time of FeLV reoccurrence. Our results demonstrate that ostensibly recovered FeLV provirus-positive cats may act as a source of infection following FeLV reactivation. The virus variants that had largely replaced the inoculation strain had unusually heavily mutated envelopes. The mutations may have led to increased viral fitness and/or changed the mutagenic characteristics of the virus.

Revisiting the genome packaging in viruses with lessons from the "Giants".

PubMed

Chelikani, Venkata; Ranjan, Tushar; Kondabagil, Kiran

2014-10-01

Genome encapsidation is an essential step in the life cycle of viruses. Viruses either use some of the most powerful ATP-dependent motors to compel the genetic material into the preformed capsid or make use of the positively charged proteins to bind and condense the negatively charged genome in an energy-independent manner. While the former is a hallmark of large DNA viruses, the latter is commonly seen in small DNA and RNA viruses. Discoveries of many complex giant viruses such as mimivirus, megavirus, pandoravirus, etc., belonging to the nucleo-cytoplasmic large DNA virus (NCLDV) superfamily have changed the perception of genome packaging in viruses. From what little we have understood so far, it seems that the genome packaging mechanism in NCLDVs has nothing in common with other well-characterized viral packaging systems such as the portal-terminase system or the energy-independent system. Recent findings suggest that in giant viruses, the genome segregation and packaging processes are more intricately coupled than those of other viral systems. Interestingly, giant viral packaging systems also seem to possess features that are analogous to bacterial and archaeal chromosome segregation. Although there is a lot of diversity in terms of host range, type of genome, and genome size among viruses, they all seem to use three major types of independent innovations to accomplish genome encapsidation. Here, we have made an attempt to comprehensively review all the known viral genome packaging systems, including the one that is operative in giant viruses, by proposing a simple and expanded classification system that divides the viral packaging systems into three large groups (types I-III) on the basis of the mechanism employed and the relatedness of the major packaging proteins. Known variants within each group have been further classified into subgroups to reflect their unique adaptations. Copyright © 2014 Elsevier Inc. All rights reserved.

Protection zone in a diffusive predator-prey model with Beddington-DeAngelis functional response.

PubMed

He, Xiao; Zheng, Sining

2017-07-01

In any reaction-diffusion system of predator-prey models, the population densities of species are determined by the interactions between them, together with the influences from the spatial environments surrounding them. Generally, the prey species would die out when their birth rate is too low, the habitat size is too small, the predator grows too fast, or the predation pressure is too high. To save the endangered prey species, some human interference is useful, such as creating a protection zone where the prey could cross the boundary freely but the predator is prohibited from entering. This paper studies the existence of positive steady states to a predator-prey model with reaction-diffusion terms, Beddington-DeAngelis type functional response and non-flux boundary conditions. It is shown that there is a threshold value [Formula: see text] which characterizes the refuge ability of prey such that the positivity of prey population can be ensured if either the prey's birth rate satisfies [Formula: see text] (no matter how large the predator's growth rate is) or the predator's growth rate satisfies [Formula: see text], while a protection zone [Formula: see text] is necessary for such positive solutions if [Formula: see text] with [Formula: see text] properly large. The more interesting finding is that there is another threshold value [Formula: see text], such that the positive solutions do exist for all [Formula: see text]. Letting [Formula: see text], we get the third threshold value [Formula: see text] such that if [Formula: see text], prey species could survive no matter how large the predator's growth rate is. In addition, we get the fourth threshold value [Formula: see text] for negative [Formula: see text] such that the system admits positive steady states if and only if [Formula: see text]. All these results match well with the mechanistic derivation for the B-D type functional response recently given by Geritz and Gyllenberg (J Theoret Biol 314:106-108, 2012). Finally, we obtain the uniqueness of positive steady states for [Formula: see text] properly large, as well as the asymptotic behavior of the unique positive steady state as [Formula: see text].

Prevalence of herpes simplex, Epstein Barr and human papilloma viruses in oral lichen planus.

PubMed

Yildirim, Benay; Sengüven, Burcu; Demir, Cem

2011-03-01

The aim of the present study was to assess the prevalence of Herpes Simplex virus, Epstein Barr virus and Human Papilloma virus -16 in oral lichen planus cases and to evaluate whether any clinical variant, histopathological or demographic feature correlates with these viruses. The study was conducted on 65 cases. Viruses were detected immunohistochemically. We evaluated the histopathological and demographic features and statistically analysed correlation of these features with Herpes Simplex virus, Epstein Barr virus and Human Papilloma virus-16 positivity. Herpes Simplex virus was positive in six (9%) cases and this was not statistically significant. The number of Epstein Barr virus positive cases was 23 (35%) and it was statistically significant. Human Papilloma virus positivity in 14 cases (21%) was statistically significant. Except basal cell degeneration in Herpes Simplex virus positive cases, we did not observe any significant correlation between virus positivity and demographic or histopathological features. However an increased risk of Epstein Barr virus and Human Papilloma virus infection was noted in oral lichen planus cases. Taking into account the oncogenic potential of both viruses, oral lichen planus cases should be detected for the presence of these viruses.

AIDS with acute cerebral infarct: a case report.

PubMed

Wu, Lin-Hui; Chen, Wei-Hung; Lien, Li-Ming; Huang, Chien-Hsien; Chiu, Hou-Chang

2005-06-01

A 38 year-old male presented with an acute onset of left hemiplegia. Brain magnetic resonance imaging (MRI) revealed a bright lesion by diffusion-weighted imaging with low apparent diffusion coefficient value in the right subcortical region, a finding compatible with an acute cerebral infarct. An old infarct was also noted in the same imaging. Both enzyme-linked immunosorbent assay and Western blot method were positive for human immunodeficiency virus infection. The white blood cell count was 2930 cells / mm3, and the subpopulation study for lymphocyte revealed a decreased cluster of differentiation 4+ count of 149 cells/mm3. Studies for prothrombotic states showed decreased protein S and increased anticardiolipin antibodies. We concluded that this was a case of acquired immunodeficiency syndrome (AIDS) with acute and old cerebral infarcts. This patient might be the first reported case in Taiwan. AIDS might be related with stroke in young patients, a condition probably under-recognized in Taiwan.

Identification of swine influenza A virus and Stenotrophomonas maltophilia co-infection in Chinese pigs

PubMed Central

2012-01-01

Background Influenza virus virulence can be exacerbated by bacterial co-infections. Swine influenza virus (SIV) infection together with some bacteria is found to enhance pathogenicity. Methods SIV-positive samples suspected of containing bacteria were used for bacterial isolation and identification. Antimicrobial susceptibility testing was performed by disc diffusion methods. To investigate the interaction of SIV and the bacteria in vitro, guinea pigs were used as mammalian hosts to determine the effect on viral susceptibility and transmissibility. Differences in viral titers between groups were compared using Student’s t-test. Results During surveillance for SIV in China from 2006 to 2009, seven isolates (24.14%) of 29 influenza A viruses were co-isolated with Stenotrophomonas maltophilia from nasal and tracheal swab samples of pigs. Antimicrobial susceptibility testing showed that the bacteria possessed a high level of resistance towards clinically used antibiotics. To investigate the interaction between these two microorganisms in influencing viral susceptibility and transmission in humans, guinea pigs were used as an infection model. Animals were inoculated with SIV or S. maltophilia alone or co-infected with SIV and S. maltophilia. The results showed that although no transmission among guinea pigs was observed, virus–bacteria co-infections resulted in higher virus titers in nasal washes and trachea and a longer virus shedding period. Conclusions This is the first report of influenza virus co-infection with S. maltophilia in the Chinese swine population. Increased replication of virus by co-infection with multidrug resistant bacteria might increase the infection rate of SIV in humans. The control of S. maltophilia in clinics will contribute to reducing the spread of SIV in pigs and humans. PMID:22913775

An unusual case of diffuse Merkel cell carcinoma successfully treated with low dose radiotherapy.

PubMed

Chatzinasiou, Foteini; Papadavid, Euaggelia; Korkolopoulou, Penelope; Levidou, Georgia; Panayiotides, Ioannis; Theodoropoulos, Konstadinos; Pogka, Vasiliki; Asimakopoulos, Charalampos; Rigopoulos, Dimitrios

2015-01-01

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of the skin. MCC should be included in the diagnosis of a rapidly growing infiltrating mass and histology as well as laboratory investigations such as Merkel cell polyoma virus (MCPyV) detection are valuable in its diagnosis. We present an unusual case of giant MCC-positive MCPyV in a Greek woman located on the lower leg. Our patient is very unusual in terms of her extensive MCC and her rapid and complete response to radiotherapy. © 2015 Wiley Periodicals, Inc.

[Pulmonary cystic disease may be a rare complication to recurrent respiratory human papilloma virus infection].

PubMed

Laurberg, Peter Thaysen; Weinreich, Ulla M Øller

2014-12-08

A 19-year-old woman with a history of juvenile laryngeal papillomatosis (JLP), treated since childhood with multiple resections, was admitted with symptoms of pneumonia. A chest X-ray and CAT-scan revealed multiple lung cysts and a bronchoalveolar lavage detected human papilloma virus 11. The patient responded well to antibiotics. A body plethysmography showed small lung volumes and low diffusion capacity for carbon monoxide, but normal volume diffusion capacity divided by alveolar volume. Pulmonary cystic disease should be considered when patients with JLP have symptoms of pneumonia.

Brain Microstructural Correlates of Cognitive Dysfunction in Clinically and Biochemically Normal Hepatitis C Virus Infection.

PubMed

Kumar, Ajay; Deep, Amar; Gupta, Rakesh K; Atam, Virendra; Mohindra, Samir

2017-09-01

This study examined correlates of the brain's neurocognitive performance among clinically and biochemically normal adult patient with hepatitis C virus (HCV). We hypothesized that anti-HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using diffusion tensor tractrography (DTT) metrics. Anti-HCV positive patient ( n  = 40), and healthy controls ( n  = 31), fulfilling inclusion criteria (incidentally detected anti-HCV positive) and able to provide informed consent were screened and recruited for the study. All these subjects and controls underwent subjective assessment of their quality of life related symptoms, neuropsychometric tests (NPT) and magnetic resonance imaging. The patients were subjected to neuroimaging as well as psychological testing. There was no significant difference in basic laboratory parameters in these two groups. Independent t -test reveals significantly lower neuropsychological functioning as compared to healthy control. A significantly decreased FA values and myoinsitol were observed in HCV subjects on sensory, inferior longitudinal fascicules, and STR fiber bundles as compared to healthy control. Bivariate correlation analysis reveals that neuropsychological scores are significantly positive. Our result show that HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using DTT metrics.

Productive infection of Epstein-Barr virus (EBV) in EBV-genome-positive epithelial cell lines (GT38 and GT39) derived from gastric tissues.

PubMed

Takasaka, N; Tajima, M; Okinaga, K; Satoh, Y; Hoshikawa, Y; Katsumoto, T; Kurata, T; Sairenji, T

1998-08-01

We characterized the expression of Epstein-Barr virus (EBV) on two epithelial cell lines, GT38 and GT39, derived from human gastric tissues. The EBV nuclear antigen (EBNA) was detected in all cells of both cell lines. The EBV immediate-early BZLF 1 protein (ZEBRA), the early antigen diffuse component (EA-D), and one of the EBV envelope proteins (gp350/220) were expressed spontaneously in small proportions in the cells. EBNA 1, EBNA2, latent membrane protein 1, ZEBRA, and EA-D molecules were then observed by Western blotting in the cells. The lytic cycle was enhanced with treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or n-butyrate. The virus particles were observed in the TPA treated GT38 cells by electron microscopy. Infectious EBV was detected with the transformation of cord blood lymphocytes and also with the induction of early antigen to Raji cells by the supernatants of both cells lines. A major single and minor multiple fused terminal fragments and a ladder of smaller fragments of the EBV genome were detected with a Xhol probe in both cell lines. These epithelial cells lines and viruses will be useful in studying their association with EBV in gastric epithelial cells.

Seroprevalence study on the diffusion of the West Nile virus among blood donors, healthcare workers, jockeys, grooms and fowlers, veterinary surgeons and hunters in Messina (Italy).

PubMed

Spataro, P; Scoglio, M E; Di Pietro, A; Chirico, C; Visalli, G; Macrì, B; Cannavò, G; Picerno, I

2008-03-01

West Nile virus (WNV) is a mosquito-transmitted flavivirus widely distributed in Africa, Middle East, Asia, Southern Europe and in 1999 was first identified in the United States as a cause of disease in New York City. It mainly circulates among birds, but can infect many species of mammals. Epidemics can occur in rural as well as urban areas. 1,280 sera were collected during 2006 from 80 stable workers, as jockey and grooms, 100 fowlers, 500 blood donors, 600 healthcare workers, 100 veterinary surgeons and 100 hunters in the Messina province to evaluate the prevalence of the WNV infection, by ELISA test, in relation to risk exposure or not. None of the 1280 subjects examined has shown positive for antibodies anti WN virus. Among the strategies of control and surveillance, finally, in our opinion, are and will be indispensable the programs of continuous antibody survey in all the risk categories and in the general population in order to succeed to preview which effects could have the presence of infections from WNV, also imported from other zones where the virus is constantly present, in future and which it could be the impact of geographic factors on the epidemic spread of the disease.

Electron microscopy of antigen precipitates extracted from gel diffusion plates

PubMed Central

Watson, D. H.; Le Bouvier, G. L.; Tomlinson, J. A.; Walkey, D. G. A.

1966-01-01

A method is described whereby material from virus precipitin lines from agar gel diffusion plates may be examined in the electron microscope by a negative staining technique. ImagesFIGS. 1-2FIGS. 3-4 PMID:4286708

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface.

PubMed

Knodel, Markus M; Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; Targett-Adams, Paul; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

2018-01-08

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

PubMed Central

Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

2018-01-01

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles. PMID:29316722

Frequent coexistence of Lewy bodies and neurofibrillary tangles in the same neurons of patients with diffuse Lewy body disease.

PubMed

Iseki, E; Marui, W; Kosaka, K; Uéda, K

1999-04-09

We examined the frequency of neurons with coexistent Lewy bodies (LB) and neurofibrillary tangles (NFT) in diffuse Lewy body disease brains, by a double-immunostaining method using MDV2 and Human tau. Double-positive neurons were frequently observed in the limbic areas. These neurons mostly revealed the feature of intermingled MDV2- and Human tau-positive substances. Immunoelectron microscopically, the MDV2-positive components were not in continuity with the MDV2-negative paired helical filaments (PHF). The MDV2-positive LB were surrounded by the small PHF bundles, frequently accompanied by the randomly oriented PHF within LB. In the intermingled neurons, MDV2-positive non-filamentous components without LB were found among the large PHF bundles. These non-filamentous components may represent the early stage of LB formation.

Prevalence of swine viral and bacterial pathogens in rodents and stray cats captured around pig farms in Korea.

PubMed

Truong, Quang Lam; Seo, Tae Won; Yoon, Byung-Il; Kim, Hyeon-Cheol; Han, Jeong Hee; Hahn, Tae-Wook

2013-12-30

In 2008, 102 rodents and 24 stray cats from the areas around 9 pig farms in northeast South Korea were used to determine the prevalence of the following selected swine pathogens: ten viral pathogens [porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), rotavirus, classical swine fever virus (CSFV), porcine circovirus type 2 (PCV2), encephalomyocarditis virus (EMCV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine parvovirus (PPV), pseudorabies virus (PRV) and Japanese encephalitis virus (JEV)] and four bacterial pathogens (Brucella, Leptospira, Salmonella and Lawsonia intracellularis). In total, 1,260 tissue samples from 102 rodents and 24 stray cats were examined by specific PCR and RT-PCR assays, including tissue samples of the brain, tonsils, lungs, heart, liver, kidneys, spleen, small intestine, large intestine and mesenteric lymph nodes. The percentages of PCR-positive rodents for the porcine pathogens were as follows: 63.7% for Leptospira, 39.2% for Brucella, 6.8% for Salmonella, 15.7% for L. intracellularis, 14.7% for PCV2 and 3.9% for EMCV. The percentages of PCR-positive stray cats for the swine pathogens were as follows: 62.5% for Leptospira, 25% for Brucella, 12.5% for Salmonella, 12.5% for L. intracellularis and 4.2% for PEDV. These results may be helpful for developing control measures to prevent the spread of infectious diseases of pigs.

[Primary central nervous system diffuse large B cell lymphoma: a clinicopathologic and molecular study].

PubMed

Ma, Z P; Ainiwaer, Babayi; Liu, Z Y; Shi, X L; Cui, W L; Zhang, W; Li, X X

2016-11-08

Objective: To investigate clinicopathologic characteristics, immunophenotype and EB virus-related molecular genetic alterations in primary central nervous system diffuse large B cell lymphoma (DLBCL) along with correlation with clinical prognosis. Methods: A total of 30 cases of primary central nervous system DLBCL were retrospectively studied by retrieving clinical data, histological evaluation and immunophenotyping by EnVision two steps methods. The expression of EBER mRNA was detected by in situ hybridization and bcl-2, bcl-6 and C-MYC gene abnormalities were analyzed by interphase fluorescence in situ hybridization. Results: The cases included 18 males and 12 females (sex ratio of 1.5∶1.0) with an age ranging from 24 to 78 years (average age of 52 years, the median age of 53 years). The single primary clinical presentation was focal neurologic deficits. Tumor locations were supratentorial (21 cases), subtentorial (7 cases), involving both locations in 2 cases. Diffuse growth pattern was observed with large lymphoid cells mostly resembling centroblasts with abundant basophilic cytoplasm with oval to round, vesicular nuclei containing fine chromatin. An angiocentric and angiodestructive growth pattern was also present. Other features included perivascular space invasion. Immunohistochemical staining using a panel of CD10, bcl-6 and MUM1, six cases were germinal center-like (GCB) and 24 cases were non-germinal central-like (non-GCB). The positive rates of bcl-2, bcl-6 and C-MYC were 53.3% (16/30), 80.0% (24/30) and 20.0% (6/30), respectively. Genetic alterations were detected by FISH and the gene arrangement rates of bcl-2, bcl-6 and C-MYC were 3.3% (1/30), 16.7% (5/30) and 3.3% (1/30), respectively. There were 19 cases in stage 0-1 disease and 11 cases had stage 2-3 disease. Postoperative follow-up for average 13.6 months showed the median survival of 10 months, one-year survival of 46.7% and 16 patients died within a year. Conclusions: The clinical prognosis of primary central nerve system DLBCL depends on age, clinical performence status score, IPI score, immune classification and treatment. Patients typically progress rapidly with the high mortality within one year of diagnosis. Surgical resection combined with high-dose methotrexate or cytarabine chemotherapy offer the best treatment option.

Molecular and Structural Basis for the Roles of Hepatitis C Virus Polymerase NS5B Amino Acids 15, 223, and 321 in Viral Replication and Drug Resistance

PubMed Central

Mosley, Ralph T.; Murakami, Eisuke; Bansal, Shalini; Lugo, Christopher; Bao, Haiying; Otto, Michael J.; Sofia, Michael J.; Furman, Phillip A.

2014-01-01

Resistance to the 2′-F-2′-C-methylguanosine monophosphate nucleotide hepatitis C virus (HCV) inhibitors PSI-352938 and PSI-353661 was associated with a combination of amino acid changes (changes of S to G at position 15 [S15G], C223H, and V321I) within the genotype 2a nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase. To understand the role of these residues in viral replication, we examined the effects of single and multiple point mutations on replication fitness and inhibition by a series of nucleotide analog inhibitors. An acidic residue at position 15 reduced replicon fitness, consistent with its proximity to the RNA template. A change of the residue at position 223 to an acidic or large residue reduced replicon fitness, consistent with its proposed proximity to the incoming nucleoside triphosphate (NTP). A change of the residue at position 321 to a charged residue was not tolerated, consistent with its position within a hydrophobic cavity. This triple resistance mutation was specific to both genotype 2a virus and 2′-F-2′-C-methylguanosine inhibitors. A crystal structure of the NS5B S15G/C223H/V321I mutant of the JFH-1 isolate exhibited rearrangement to a conformation potentially consistent with short primer-template RNA binding, which could suggest a mechanism of resistance accomplished through a change in the NS5B conformation, which was better tolerated by genotype 2a virus than by viruses of other genotypes. PMID:25182647

Finite Volume Scheme for Double Convection-Diffusion Exchange of Solutes in Bicarbonate High-Flux Hollow-Fiber Dialyzer Therapy

PubMed Central

Annan, Kodwo

2012-01-01

The efficiency of a high-flux dialyzer in terms of buffering and toxic solute removal largely depends on the ability to use convection-diffusion mechanism inside the membrane. A two-dimensional transient convection-diffusion model coupled with acid-base correction term was developed. A finite volume technique was used to discretize the model and to numerically simulate it using MATLAB software tool. We observed that small solute concentration gradients peaked and were large enough to activate solute diffusion process in the membrane. While CO2 concentration gradients diminished from their maxima and shifted toward the end of the membrane, HCO3 − concentration gradients peaked at the same position. Also, CO2 concentration decreased rapidly within the first 47 minutes while optimal HCO3 − concentration was achieved within 30 minutes of the therapy. Abnormally high diffusion fluxes were observed near the blood-membrane interface that increased diffusion driving force and enhanced the overall diffusive process. While convective flux dominated total flux during the dialysis session, there was a continuous interference between convection and diffusion fluxes that call for the need to seek minimal interference between these two mechanisms. This is critical for the effective design and operation of high-flux dialyzers. PMID:23197994

Approaches and Perspectives for Development of African Swine Fever Virus Vaccines

PubMed Central

Arias, Marisa; de la Torre, Ana; Dixon, Linda; Gallardo, Carmina; Laddomada, Alberto; Martins, Carlos; Parkhouse, R. Michael; Revilla, Yolanda; Rodriguez, Fernando; Sanchez-Vizcaino, Jose-Manuel

2017-01-01

African swine fever (ASF) is a complex disease of swine, caused by a large DNA virus belonging to the family Asfarviridae. The disease shows variable clinical signs, with high case fatality rates, up to 100%, in the acute forms. ASF is currently present in Africa and Europe where it circulates in different scenarios causing a high socio-economic impact. In most affected regions, control has not been effective in part due to lack of a vaccine. The availability of an effective and safe ASFV vaccines would support and enforce control–eradication strategies. Therefore, work leading to the rational development of protective ASF vaccines is a high priority. Several factors have hindered vaccine development, including the complexity of the ASF virus particle and the large number of proteins encoded by its genome. Many of these virus proteins inhibit the host’s immune system thus facilitating virus replication and persistence. We review previous work aimed at understanding ASFV–host interactions, including mechanisms of protective immunity, and approaches for vaccine development. These include live attenuated vaccines, and “subunit” vaccines, based on DNA, proteins, or virus vectors. In the shorter to medium term, live attenuated vaccines are the most promising and best positioned candidates. Gaps and future research directions are evaluated. PMID:28991171

Isolation and characterization of Nylanderia fulva virus 1, a positive-sense, single-stranded RNA virus infecting the tawny crazy ant, Nylanderia fulva

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valles, Steven M., E-mail: steven.valles@ars.usda.gov; Oi, David H.; Becnel, James J.

We report the discovery of Nylanderia fulva virus 1 (NfV-1), the first virus identified and characterized from the ant, Nylanderia fulva. The NfV-1 genome (GenBank accession KX024775) is 10,881 nucleotides in length, encoding one large open reading frame (ORF). Helicase, protease, RNA-dependent RNA polymerase, and jelly-roll capsid protein domains were recognized within the polyprotein. Phylogenetic analysis placed NfV-1 in an unclassified clade of viruses. Electron microscopic examination of negatively stained samples revealed particles with icosahedral symmetry with a diameter of 28.7±1.1 nm. The virus was detected by RT-PCR in larval, pupal, worker and queen developmental stages. However, the replicative strandmore » of NfV-1 was only detected in larvae. Vertical transmission did not appear to occur, but horizontal transmission was facile. The inter-colonial field prevalence of NfV-1 was 52±35% with some local infections reaching 100%. NfV-1 was not detected in limited samples of other Nylanderia species or closely related ant species. - Highlights: • A new positive-strand RNA virus was discovered in the ant, Nylanderia fulva. • The Nylanderia fulva virus 1 genome was comprised of 10,881 nucleotides. • NfV-1 was detected in larval, pupal, queen and worker ants, but not eggs. • Replication of NfV-1 appeared to be limited to the larval stage.« less

Characterization of H7 Influenza A Virus in Wild and Domestic Birds in Korea

PubMed Central

Kang, Hyun-Mi; Park, Ha-Young; Lee, Kyu-Jun; Choi, Jun-Gu; Lee, Eun-Kyoung; Song, Byung-Min; Lee, Hee-Soo; Lee, Youn-Jeong

2014-01-01

During surveillance programs in Korea between January 2006 and March 2011, 31 H7 avian influenza viruses were isolated from wild birds and domestic ducks and genetically characterized using large-scale sequence data. All Korean H7 viruses belonged to the Eurasian lineage, which showed substantial genetic diversity, in particular in the wild birds. The Korean H7 viruses from poultry were closely related to those of wild birds. Interestingly, two viruses originating in domestic ducks in our study had the same gene constellations in all segment genes as viruses originating in wild birds. The Korean H7 isolates contained avian-type receptors (Q226 and G228), no NA stalk deletion (positions 69–73), no C-terminal deletion (positions 218–230) in NS1, and no substitutions in PB2-627, PB1-368, and M2-31, compared with H7N9 viruses. In pathogenicity experiments, none of the Korean H7 isolates tested induced clinical signs in domestic ducks or mice. Furthermore, while they replicated poorly, with low titers (10 0.7–1.3EID50/50 µl) in domestic ducks, all five viruses replicated well (up to 7–10 dpi, 10 0.7–4.3EID50/50 µl) in the lungs of mice, without prior adaptation. Our results suggest that domestic Korean viruses were transferred directly from wild birds through at least two independent introductions. Our data did not indicate that wild birds carried poultry viruses between Korea and China, but rather, that wild-type H7 viruses were introduced several times into different poultry populations in eastern Asia. PMID:24776918

Expression of activation-induced cytidine deaminase is associated with a poor prognosis of diffuse large B cell lymphoma patients treated with CHOP-based chemotherapy.

PubMed

Kawamura, Kiyoko; Wada, Akihiko; Wang, Ji-Yang; Li, Quanhai; Ishii, Akihiro; Tsujimura, Hideki; Takagi, Toshiyuki; Itami, Makiko; Tada, Yuji; Tatsumi, Koichiro; Shimada, Hideaki; Hiroshima, Kenzo; Tagawa, Masatoshi

2016-01-01

Activation-induced cytidine deaminase (AID) is involved in somatic hypermutation and class switch recombination processes in the antibody formation. The AID activity induces gene mutations and could be associated with transformation processes of B cells. Nevertheless, the relation between AID expression and the prognosis of B cell lymphoma patients remains uncharacterized. We examined expression levels of the AID gene in 89 lymph node specimens from lymphoma and non-lymphoma patients with Northern blot analysis and investigated an association with their survival. The AID gene was preferentially expressed in B cell lymphoma in particular in diffuse large B cell lymphoma and follicular lymphoma. We confirmed AID protein expression in the mRNA-positive but not in the negative specimens with Western blot analysis and immunohistochemical staining. Survival of the patients treated with cyclophosphamide-/doxorubicin-/vincristine-/prednisone-based chemotherapy demonstrated that the prognosis of diffuse large B cell patients was unfavorable in the mRNA-positive group compared with the negative group, and that AID expression levels were correlated with the poor prognosis. In contrast, AID expression was not linked with the prognosis of follicular lymphoma patients. AID expression is a predictive marker for an unfavorable outcome in DLBCL patients treated with the chemotherapy.

Isolation and characterization of Solenopsis invicta virus 3, a new positive-strand RNA virus infecting the red imported fire ant, Solenopsis invicta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valles, Steven M., E-mail: Steven.Valles@ars.usda.go; Hashimoto, Yoshifumi

2009-06-05

We report the discovery of a new virus from the red imported fire ant, Solenopsis invicta. Solenopsis invicta virus 3 (SINV-3) represents the third virus discovered from this ant species using the metagenomics approach. The single (positive)-strand RNA, monopartite, bicistronic genome of SINV-3 was sequenced in entirety (GenBank accession number (FJ528584)), comprised of 10,386 nucleotides, and polyadenylated at the 3' terminus. This genome size was confirmed by Northern analysis. The genome revealed 2 large open reading frames (ORFs) in the sense orientation with an untranslated region (UTR) at each end and between the two ORFs. The 5' proximal ORF (ORFmore » 1) encoded a predicted protein of 299.1 kDa (2580 amino acids). The 3' proximal ORF (ORF 2) encoded a predicted protein of 73.2 kDa (651 amino acids). RNA-dependent RNA polymerase (RdRp), helicase, and protease domains were recognized in ORF 1. SDS-PAGE separation of purified SINV-3 particles yielded 2 bands (ostensibly capsid proteins) with a combined molecular mass of 77.3 kDa which was similar to the mass predicted by ORF 2 (73.2 kDa). Phylogenetic analysis of the conserved amino acid sequences containing domains I to VIII of the RdRp from dicistroviruses, iflaviruses, plant small RNA viruses, picornaviruses, and 4 unassigned positive-strand RNA viruses revealed a trichotomous phenogram with SINV-3 and Kelp fly virus comprising a unique cluster. Electron microscopic examination of negatively stained samples of SINV-3 revealed isometric particles with apparent projections and a diameter of 27.3 +- 1.3 nm. SINV-3 was successfully transmitted to uninfected workers by feeding. The minus (replicative) strand of SINV-3 was detected in worker ants indicating replication of the virus. The possibility of using SINV-3 as a microbial control agent for fire ants is discussed.« less

A universal protocol to generate consensus level genome sequences for foot-and-mouth disease virus and other positive-sense polyadenylated RNA viruses using the Illumina MiSeq.

PubMed

Logan, Grace; Freimanis, Graham L; King, David J; Valdazo-González, Begoña; Bachanek-Bankowska, Katarzyna; Sanderson, Nicholas D; Knowles, Nick J; King, Donald P; Cottam, Eleanor M

2014-09-30

Next-Generation Sequencing (NGS) is revolutionizing molecular epidemiology by providing new approaches to undertake whole genome sequencing (WGS) in diagnostic settings for a variety of human and veterinary pathogens. Previous sequencing protocols have been subject to biases such as those encountered during PCR amplification and cell culture, or are restricted by the need for large quantities of starting material. We describe here a simple and robust methodology for the generation of whole genome sequences on the Illumina MiSeq. This protocol is specific for foot-and-mouth disease virus (FMDV) or other polyadenylated RNA viruses and circumvents both the use of PCR and the requirement for large amounts of initial template. The protocol was successfully validated using five FMDV positive clinical samples from the 2001 epidemic in the United Kingdom, as well as a panel of representative viruses from all seven serotypes. In addition, this protocol was successfully used to recover 94% of an FMDV genome that had previously been identified as cell culture negative. Genome sequences from three other non-FMDV polyadenylated RNA viruses (EMCV, ERAV, VESV) were also obtained with minor protocol amendments. We calculated that a minimum coverage depth of 22 reads was required to produce an accurate consensus sequence for FMDV O. This was achieved in 5 FMDV/O/UKG isolates and the type O FMDV from the serotype panel with the exception of the 5' genomic termini and area immediately flanking the poly(C) region. We have developed a universal WGS method for FMDV and other polyadenylated RNA viruses. This method works successfully from a limited quantity of starting material and eliminates the requirement for genome-specific PCR amplification. This protocol has the potential to generate consensus-level sequences within a routine high-throughput diagnostic environment.

Epstein-Barr Virus Sequence Variation—Biology and Disease

PubMed Central

Tzellos, Stelios; Farrell, Paul J.

2012-01-01

Some key questions in Epstein-Barr virus (EBV) biology center on whether naturally occurring sequence differences in the virus affect infection or EBV associated diseases. Understanding the pattern of EBV sequence variation is also important for possible development of EBV vaccines. At present EBV isolates worldwide can be grouped into Type 1 and Type 2, a classification based on the EBNA2 gene sequence. Type 1 EBV is the most prevalent worldwide but Type 2 is common in parts of Africa. Type 1 transforms human B cells into lymphoblastoid cell lines much more efficiently than Type 2 EBV. Molecular mechanisms that may account for this difference in cell transformation are now becoming clearer. Advances in sequencing technology will greatly increase the amount of whole EBV genome data for EBV isolated from different parts of the world. Study of regional variation of EBV strains independent of the Type 1/Type 2 classification and systematic investigation of the relationship between viral strains, infection and disease will become possible. The recent discovery that specific mutation of the EBV EBNA3B gene may be linked to development of diffuse large B cell lymphoma illustrates the importance that mutations in the virus genome may have in infection and human disease. PMID:25436768

Drug Reaction with Eosinophilia and Systemic Symptoms Associated with Reactivation of Epstein-Barr Virus and/or Cytomegalovirus Leading to Hemophagocytic Syndrome in One of Two Patients

PubMed Central

Liang, Jianhua; Qu, Hui; Wang, Xiaowen; Wang, Aiping; Liu, Lingling; Tu, Ping; Li, Ruoyu

2018-01-01

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity reaction characterized by maculopapular rash, exfoliative dermatitis, lymphadenopathy, fever, eosinophilia, and involvement of internal organs. Evidence for reactivation of herpes family viruses has been observed in some DRESS patients, and activated CD8+ T lymphocytes are largely directed against Epstein-Barr virus. Here, we report two cases complicated with this infection. Both patients received antibiotics and non-steroidal anti-inflammatory drugs. These patients manifested clinically with high fever, facial edema, diffuse pruritic erythroderma and maculopapules over the entire body, purpuric rashes in both lower limbs and lymphadenopathy of cervical and inguinal nodes. Laboratory tests revealed abnormal liver function, blood eosinophils, and ferritin levels. The patients recovered completely; however, the female patient developed hemophagocytic syndrome on the 15th day of illness. She developed new itchy rash, and laboratory tests rapidly worsened with fibrinogen levels dramatically reduced to 0.61 g/L. Bone marrow aspiration revealed an increased number of macrophages with hemophagocytosis and a reversed CD4/CD8 ratio of 0.45. These cases suggest that human herpes virus and coagulation function evaluations are necessary in DRESS patients. PMID:29386835

Persistence of chicken anemia virus antigen and inclusions in spontaneous cases of Marek's disease visceral lymphomas in broiler chickens at slaughterhouses.

PubMed

Ahmed, Mohamed Sabry; Ono, Hiroki; Sasaki, Jun; Ochiai, Kenji; Goryo, Masanobu

2016-06-01

The chicken anemia virus (CAV) and Marek's disease virus (MDV) infect chickens worldwide; a single or dual infection by these viruses has a great impact on poultry production. In the present study, we examined the existence of CAV antigen and its inclusions in Marek's disease (MD) lymphomas in chickens in the slaughterhouses of Iwate prefecture, Japan. Forty-nine spleens and 13 livers with different degrees of nodular lesions were histopathologically examined at our laboratory. Grossly, the tested organs showed various sizes and anatomical architectures. Based on the cellular morphology and the infiltrative nature of the neoplastic lymphocytes, MD was confirmed in 76% (37/49) of the spleens and 92% (12/13) of the livers. The lesions of MD, according to the pattern of lymphocytic accumulation in the affected organs, were divided into multifocal, coalesced and diffuse. CAV intranuclear inclusion bodies were detected within the small and the large bizarre lymphocytes of the MD lymphomas in 2 livers and 9 spleens, and the immunostaining test for CAV confirmed the persistence of CAV antigens and inclusions in the neoplastic cells. This study demonstrated the persistence of CAV infection within the neoplastic cells of naturally occurring MD lymphomas in chickens.

Prevalence and Pathology of West Nile Virus in Naturally Infected House Sparrows, Western Nebraska, 2008

PubMed Central

O'Brien, Valerie A.; Meteyer, Carol U.; Reisen, William K.; Ip, Hon S.; Brown, Charles R.

2010-01-01

Nestling birds are rarely sampled in the field for most arboviruses, yet they may be important in arbovirus amplification cycles. We sampled both nestling and adult house sparrows (Passer domesticus) in western Nebraska for West Nile virus (WNV) or WNV-specific antibodies throughout the summer of 2008 and describe pathology in naturally infected nestlings. Across the summer, 4% of nestling house sparrows were WNV-positive; for the month of August alone, 12.3% were positive. Two WNV-positive nestlings exhibited encephalitis, splenomegaly, hepatic necrosis, nephrosis, and myocarditis. One nestling sparrow had large mural thrombi in the atria and ventricle and immunohistochemical staining of WNV antigen in multiple organs including the wall of the aorta and pulmonary artery; cardiac insufficiency thus may have been a cause of death. Adult house sparrows showed an overall seroprevalence of 13.8% that did not change significantly across the summer months. The WNV-positive nestlings and the majority of seropositive adults were detected within separate spatial clusters. Nestling birds, especially those reared late in the summer when WNV activity is typically greatest, may be important in virus amplification. PMID:20439979

Ascites as the initial characteristic manifestation in a patient with primary gastric CD8-positive diffuse large B-cell lymphoma.

PubMed

Zhao, K-X; Dai, G-Z; Zhu, J-F

2016-05-01

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy and the most common type of non-Hodgkin's lymphomas, the stomach is the most common extranodal site. Gastric DLBCL is often characterized by epigastric pain and vomiting. We report a case of a 78-year-old female patient with gastric diffuse large B-cell lymphoma (DLBCL) with high CD8 level which was initially manifested with ascites of unknown origin. The patient was admitted with a chief complaint of abdominal distension and scanty urine over the last twenty days, while without anorexia and fatigue until 15 March. She had no history of viral hepatitis, tuberculosis, schistosomiasis. Laboratory data revealed normal aminotransferases and bilirubin levels, but serum lactate dehydrogenase, CA125, ascitic fluid lactate dehydrogenase, ascitic fluid lymphocytes increased. The ascitic fluid was yellow-colored with 98.5% lymphocytes. Stool occult blood test was positive. Upper gastrointestinal endoscopy performed a few days later revealed multiple gastric crateriform ulcers, and Helicobacter pylori was detected in the biopsy specimen. Peripheral blood CD8+ was increased by 51%. Pathology test showed lymphocytes with atypical hyperplasia, and immunohistochemistry test resulted CD20+, CD10-, CD79α+, κ+, bcl-6+, Ki-67+ (approximately 95%), λ-, bcl-2-, CD3-, CD43-. Immunoglobulin gene (Ig) clonal rearrangement showed IgH: FR1 (+), FR2 (+), FR3(-), Igk: VJ(+), Vkde (+) in lymphoma tissue. The features of histopathology and immunohistochemistry of the tissue confirmed diffuse large B-cell lymphoma (DLBL). The patient received an uncompleted CHOP program combined with H. pylori eradication. However, the patient deceased due to disease development sixteen days later after the diagnosis.

Seroprevalence of fowl pox antibody in indigenous chickens in jos north and South council areas of plateau state, Nigeria: implication for vector vaccine.

PubMed

Adebajo, Meseko Clement; Ademola, Shittu Ismail; Oluwaseun, Akinyede

2012-01-01

Fowl pox is a viral disease of domestic and wild birds. The large size of the genome makes it a useful vector for recombinant DNA technology. Although the disease has been described in both commercial and indigenous chickens in Nigeria, data are limited on seroprevalence in free range chickens. Such data are, however, important in the design and implementation of fowl pox virus vector vaccine. We surveyed current antibody status to fowl pox virus in free range chickens by testing 229 sera collected from 10 villages in Jos North and Jos South LGA of Plateau State Nigeria. Sera were analyzed by AGID against standard fowl pox antigen. Fifty-two of the 229 (23%) tested sera were positive for fowl pox virus antibody, and the log titre in all positive specimen was >2. Thirty (21%) and twenty-two (27%) of the samples from Jos South and Jos North, respectively, tested positive. This was, however, not statistically significant (P = 0.30). Generally the study showed a significant level of antibody to fowl pox virus in the study area. This observation may hinder effective use of fowl pox vectored viral vaccine. Fowl pox control is recommended to reduce natural burden of the disease.

Seroprevalence of Fowl Pox Antibody in Indigenous Chickens in Jos North and South Council Areas of Plateau State, Nigeria: Implication for Vector Vaccine

PubMed Central

Adebajo, Meseko Clement; Ademola, Shittu Ismail; Oluwaseun, Akinyede

2012-01-01

Fowl pox is a viral disease of domestic and wild birds. The large size of the genome makes it a useful vector for recombinant DNA technology. Although the disease has been described in both commercial and indigenous chickens in Nigeria, data are limited on seroprevalence in free range chickens. Such data are, however, important in the design and implementation of fowl pox virus vector vaccine. We surveyed current antibody status to fowl pox virus in free range chickens by testing 229 sera collected from 10 villages in Jos North and Jos South LGA of Plateau State Nigeria. Sera were analyzed by AGID against standard fowl pox antigen. Fifty-two of the 229 (23%) tested sera were positive for fowl pox virus antibody, and the log titre in all positive specimen was >2. Thirty (21%) and twenty-two (27%) of the samples from Jos South and Jos North, respectively, tested positive. This was, however, not statistically significant (P = 0.30). Generally the study showed a significant level of antibody to fowl pox virus in the study area. This observation may hinder effective use of fowl pox vectored viral vaccine. Fowl pox control is recommended to reduce natural burden of the disease. PMID:23762578

Bluetongue and epizootic haemorrhagic disease virus in local breeds of cattle in Kenya.

PubMed

Toye, P G; Batten, C A; Kiara, H; Henstock, M R; Edwards, L; Thumbi, S; Poole, E J; Handel, I G; Bronsvoort, B M deC; Hanotte, O; Coetzer, J A W; Woolhouse, M E J; Oura, C A L

2013-06-01

The presence of bluetongue virus (BTV) and Epizootic Haemorrhagic Disease virus (EHDV) in indigenous calves in western Kenya was investigated. Serum was analysed for BTV and EHDV antibodies. The population seroprevalences for BTV and EHDV for calves at 51 weeks of age were estimated to be 0.942 (95% CI 0.902-0.970) and 0.637 (95% CI 0.562-0.710), respectively, indicating high levels of circulating BTV and EHDV. The odds ratio of being positive for BTV if EHDV positive was estimated to be 2.57 (95% CI 1.37-4.76). When 99 calves were tested for BTV and EHDV RNA by real-time RT-PCR, 88.9% and 63.6% were positive, respectively. Comparison of the serology and real-time RT-PCR results revealed an unexpectedly large number of calves that were negative by serology but positive by real-time RT-PCR for EHDV. Eight samples positive for BTV RNA were serotyped using 24 serotype-specific real-time RT-PCR assays. Nine BTV serotypes were detected, indicating that the cattle were infected with a heterogeneous population of BTVs. The results show that BTV and EHDV are highly prevalent, with cattle being infected from an early age. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bluetongue and Epizootic Haemorrhagic Disease virus in local breeds of cattle in Kenya

PubMed Central

Toye, P.G.; Batten, C.A.; Kiara, H.; Henstock, M.R.; Edwards, L.; Thumbi, S.; Poole, E.J.; Handel, I.G.; Bronsvoort, B.M.deC.; Hanotte, O.; Coetzer, J.A.W.; Woolhouse, M.E.J.; Oura, C.A.L.

2013-01-01

The presence of bluetongue virus (BTV) and Epizootic Haemorrhagic Disease virus (EHDV) in indigenous calves in western Kenya was investigated. Serum was analysed for BTV and EHDV antibodies. The population seroprevalences for BTV and EHDV for calves at 51 weeks of age were estimated to be 0.942 (95% CI 0.902–0.970) and 0.637 (95% CI 0.562–0.710), respectively, indicating high levels of circulating BTV and EHDV. The odds ratio of being positive for BTV if EHDV positive was estimated to be 2.57 (95% CI 1.37–4.76). When 99 calves were tested for BTV and EHDV RNA by real-time RT-PCR, 88.9% and 63.6% were positive, respectively. Comparison of the serology and real-time RT-PCR results revealed an unexpectedly large number of calves that were negative by serology but positive by real-time RT-PCR for EHDV. Eight samples positive for BTV RNA were serotyped using 24 serotype-specific real-time RT-PCR assays. Nine BTV serotypes were detected, indicating that the cattle were infected with a heterogeneous population of BTVs. The results show that BTV and EHDV are highly prevalent, with cattle being infected from an early age. PMID:23261160

Global stability and pattern formation in a nonlocal diffusive Lotka-Volterra competition model

NASA Astrophysics Data System (ADS)

Ni, Wenjie; Shi, Junping; Wang, Mingxin

2018-06-01

A diffusive Lotka-Volterra competition model with nonlocal intraspecific and interspecific competition between species is formulated and analyzed. The nonlocal competition strength is assumed to be determined by a diffusion kernel function to model the movement pattern of the biological species. It is shown that when there is no nonlocal intraspecific competition, the dynamics properties of nonlocal diffusive competition problem are similar to those of classical diffusive Lotka-Volterra competition model regardless of the strength of nonlocal interspecific competition. Global stability of nonnegative constant equilibria are proved using Lyapunov or upper-lower solution methods. On the other hand, strong nonlocal intraspecific competition increases the system spatiotemporal dynamic complexity. For the weak competition case, the nonlocal diffusive competition model may possess nonconstant positive equilibria for some suitably large nonlocal intraspecific competition coefficients.

Generation of West Nile virus infectious clones containing amino acid insertions between capsid and capsid anchor.

PubMed

Vandergaast, Rianna; Hoover, Lisa I; Zheng, Kang; Fredericksen, Brenda L

2014-04-09

West Nile virus (WNV) is a positive-sense RNA arbovirus responsible for recent outbreaks of severe neurological disease within the US and Europe. Large-scale analyses of antiviral compounds that inhibit virus replication have been limited due to the lack of an adequate WN reporter virus. Previous attempts to insert a reporter into the 3' untranslated region of WNV generated unstable viruses, suggesting that this region does not accommodate additional nucleotides. Here, we engineered two WNV infectious clones containing insertions at the Capsid (C)/Capsid Anchor (CA) junction of the viral polyprotein. Recombinant viruses containing a TAT(1-67) or Gaussia Luciferase (GLuc) gene at this location were successfully recovered. However, rapid loss of most, if not all, of the reporter sequence occurred for both viruses, indicating that the reporter viruses were not stable. While the GLuc viruses predominantly reverted back to wild-type WNV length, the TAT viruses retained up to 75 additional nucleotides of the reporter sequence. These additional nucleotides were stable over at least five passages and did not significantly alter WNV fitness. Thus, the C/CA junction of WNV can tolerate additional nucleotides, though insertions are subject to certain constraints.

Generation of West Nile Virus Infectious Clones Containing Amino Acid Insertions Between Capsid and Capsid Anchor

PubMed Central

Vandergaast, Rianna; Hoover, Lisa I.; Zheng, Kang; Fredericksen, Brenda L.

2014-01-01

West Nile virus (WNV) is a positive-sense RNA arbovirus responsible for recent outbreaks of severe neurological disease within the US and Europe. Large-scale analyses of antiviral compounds that inhibit virus replication have been limited due to the lack of an adequate WN reporter virus. Previous attempts to insert a reporter into the 3’ untranslated region of WNV generated unstable viruses, suggesting that this region does not accommodate additional nucleotides. Here, we engineered two WNV infectious clones containing insertions at the Capsid (C)/Capsid Anchor (CA) junction of the viral polyprotein. Recombinant viruses containing a TAT(1-67) or Gaussia Luciferase (GLuc) gene at this location were successfully recovered. However, rapid loss of most, if not all, of the reporter sequence occurred for both viruses, indicating that the reporter viruses were not stable. While the GLuc viruses predominantly reverted back to wild-type WNV length, the TAT viruses retained up to 75 additional nucleotides of the reporter sequence. These additional nucleotides were stable over at least five passages and did not significantly alter WNV fitness. Thus, the C/CA junction of WNV can tolerate additional nucleotides, though insertions are subject to certain constraints. PMID:24721788

Assembly, maturation and three-dimensional helical structure of the teratogenic rubella virus

PubMed Central

Mangala Prasad, Vidya

2017-01-01

Viral infections during pregnancy are a significant cause of infant morbidity and mortality. Of these, rubella virus infection is a well-substantiated example that leads to miscarriages or severe fetal defects. However, structural information about the rubella virus has been lacking due to the pleomorphic nature of the virions. Here we report a helical structure of rubella virions using cryo-electron tomography. Sub-tomogram averaging of the surface spikes established the relative positions of the viral glycoproteins, which differed from the earlier icosahedral models of the virus. Tomographic analyses of in vitro assembled nucleocapsids and virions provide a template for viral assembly. Comparisons of immature and mature virions show large rearrangements in the glycoproteins that may be essential for forming the infectious virions. These results present the first known example of a helical membrane-enveloped virus, while also providing a structural basis for its assembly and maturation pathway. PMID:28575072

Assembly, maturation and three-dimensional helical structure of the teratogenic rubella virus.

PubMed

Mangala Prasad, Vidya; Klose, Thomas; Rossmann, Michael G

2017-06-01

Viral infections during pregnancy are a significant cause of infant morbidity and mortality. Of these, rubella virus infection is a well-substantiated example that leads to miscarriages or severe fetal defects. However, structural information about the rubella virus has been lacking due to the pleomorphic nature of the virions. Here we report a helical structure of rubella virions using cryo-electron tomography. Sub-tomogram averaging of the surface spikes established the relative positions of the viral glycoproteins, which differed from the earlier icosahedral models of the virus. Tomographic analyses of in vitro assembled nucleocapsids and virions provide a template for viral assembly. Comparisons of immature and mature virions show large rearrangements in the glycoproteins that may be essential for forming the infectious virions. These results present the first known example of a helical membrane-enveloped virus, while also providing a structural basis for its assembly and maturation pathway.

The nucleotide sequence of RNA1 of Lettuce big-vein virus, genus Varicosavirus, reveals its relation to nonsegmented negative-strand RNA viruses.

PubMed

Sasaya, Takahide; Ishikawa, Koichi; Koganezawa, Hiroki

2002-06-05

The complete nucleotide sequence of RNA1 from Lettuce big-vein virus (LBVV), the type member of the genus Varicosavirus, was determined. LBVV RNA1 consists of 6797 nucleotides and contains one large ORF that encodes a large (L) protein of 2040 amino acids with a predicted M(r) of 232,092. Northern blot hybridization analysis indicated that the LBVV RNA1 is a negative-sense RNA. Database searches showed that the amino acid sequence of L protein is homologous to those of L polymerases of nonsegmented negative-strand RNA viruses. A cluster dendrogram derived from alignments of the LBVV L protein and the L polymerases indicated that the L protein is most closely related to the L polymerases of plant rhabdoviruses. Transcription termination/polyadenylation signal-like poly(U) tracts that resemble those in rhabdovirus and paramyxovirus RNAs were present upstream and downstream of the coding region. Although LBVV is related to rhabdoviruses, a key distinguishing feature is that the genome of LBVV is segmented. The results reemphasize the need to reconsider the taxonomic position of varicosaviruses.

Generalized minimal principle for rotor filaments.

PubMed

Dierckx, Hans; Wellner, Marcel; Bernus, Olivier; Verschelde, Henri

2015-05-01

To a reaction-diffusion medium with an inhomogeneous anisotropic diffusion tensor D, we add a fourth spatial dimension such that the determinant of the diffusion tensor is constant in four dimensions. We propose a generalized minimal principle for rotor filaments, stating that the scroll wave filament strives to minimize its surface area in the higher-dimensional space. As a consequence, stationary scroll wave filaments in the original 3D medium are geodesic curves with respect to the metric tensor G=det(D)D(-1). The theory is confirmed by numerical simulations for positive and negative filament tension and a model with a non-stationary spiral core. We conclude that filaments in cardiac tissue with positive tension preferentially reside or anchor in regions where cardiac cells are less interconnected, such as portions of the cardiac wall with a large number of cleavage planes.

Modeling Cryptosporidium spp. Oocyst Inactivation in Bubble-Diffuser Ozone Contactors

DTIC Science & Technology

1998-07-01

requirements for Giardia lamblia (G. lamblia) and viruses under the Surface Water Treatment Rule (SWTR). Minimum CT requirements include relatively...parvum and C. muris ) oocysts in ozone bubble-diffuser contactors. The model is calibrated with semi-batch kinetic data, verified with pilot-scale

Canine adenovirus type 1 in a fennec fox (Vulpes zerda).

PubMed

Choi, Jeong-Won; Lee, Hyun-Kyoung; Kim, Seong-Hee; Kim, Yeon-Hee; Lee, Kyoung-Ki; Lee, Myoung-Heon; Oem, Jae-Ku

2014-12-01

A 10-mo-old female fennec fox (Vulpes zerda) with drooling suddenly died and was examined postmortem. Histologic examination of different tissue samples was performed. Vacuolar degeneration and diffuse fatty change were observed in the liver. Several diagnostic methods were used to screen for canine parvovirus, canine distemper virus, canine influenza virus, canine coronavirus, canine parainfluenza virus, and canine adenovirus (CAdV). Only CAdV type 1 (CAdV-1) was detected in several organs (liver, lung, brain, kidney, spleen, and heart), and other viruses were not found. CAdV-1 was confirmed by virus isolation and nucleotide sequencing.

Kidney Disease in Human Immunodeficiency Virus-seropositive Patients: Absence of Human Immunodeficiency Virus-associated Nephropathy was a Characteristic Feature.

PubMed

Prakash, J; Ganiger, V; Prakash, S; Sivasankar, M; Sunder, S; Singh, U

2017-01-01

Human immunodeficiency virus (HIV) infection can cause a broad spectrum of renal diseases. However, there is paucity of Indian data on the patterns of renal lesions in HIV-seropositive patients. The aim of the present study was to delineate the spectrum of renal lesions in HIV/acquired immunodeficiency syndrome patients. In this prospective study, all HIV-positive patients of both genders aged >18 years were screened for renal disease. Patients with proteinuria of more than 1 g/24 h were subjected to renal biopsy. A total of 293 HIV-positive patients were screened; of these, 136 (46.4%) patients found to have renal involvement. Dipstick-positive proteinuria of 1+ or more was observed in 112 (38.2%) patients, and 16 (14.2%) patients had proteinuria of more than 1 g/24 h. Renal biopsy in 14 cases revealed glomerulonephritis (GN) in 12 (85.7%) (isolated GN in 4 [28.5%] and GN mixed with chronic TIN in 8 [57.1%]) patients. These include mesangioproliferative GN in 5 (35.7%), membranoproliferative GN in 2 (14.2%), focal segmental glomerulosclerosis in 2 (14.2%), diffuse proliferative GN in 2 (14.2%), and diabetic nephropathy in 1 (7.1%) patients. Chronic interstitial nephritis was noted in 10 (71.42%) (superimposed on GN in 8 [57.1%], isolated in 2 [14.2%]) patients. Granulomatous interstitial nephritis was seen in 3 (24.1%) cases. GN and chronic interstitial nephritis were noted in 85.7% and 71.42% of patients, respectively, mostly superimposed on each other. Mesangioproliferative GN was the most common glomerular lesion, but classical HIV-associated nephropathy was not observed.

Clinical roundtable monograph: CD30 in lymphoma: its role in biology, diagnostic testing, and targeted therapy.

PubMed

Sotomayor, Eduardo M; Young, Ken H; Younes, Anas

2014-04-01

CD30, a member of the tumor necrosis factor receptor superfamily, is a transmembrane glycoprotein receptor consisting of an extracellular domain, a transmembrane domain, and an intracellular domain. CD30 has emerged as an important molecule in the field of targeted therapy because its expression is generally restricted to specific disease types and states. The major cancers with elevated CD30 expression include Hodgkin lymphoma and anaplastic large T-cell lymphoma, and CD30 expression is considered essential to the differential diagnosis of these malignancies. Most commonly, CD30 expression is detected and performed by immunohistochemical staining of biopsy samples. Alternatively, flow cytometry analysis has also been developed for fresh tissue and cell aspiration specimens, including peripheral blood and bone marrow aspirate. Over the past several years, several therapeutic agents were developed to target CD30, with varying success in clinical trials. A major advance in the targeting of CD30 was seen with the development of the antibody-drug conjugate brentuximab vedotin, which consists of the naked anti-CD30 antibody SGN-30 conjugated to the synthetic antitubulin agent monomethyl auristatin E. In 2011, brentuximab vedotin was approved by the US Food and Drug Administration for use in Hodgkin lymphoma and anaplastic large cell lymphoma based on clinical trial data showing high response rates in these indications. Ongoing trials are examining brentuximab vedotin after autologous stem cell transplantation, as part of chemotherapy combination regimens, and in other CD30-expressing malignancies, including primary mediastinal large B-cell lymphomas, diffuse large B-cell lymphoma, lymphoma positive for Epstein-Barr virus, peripheral T-cell lymphoma not otherwise specified, and cutaneous anaplastic large cell lymphoma.

Lessons from the history of the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic among Spanish drug injectors.

PubMed

De La Fuente, L; Bravo, M J; Barrio, G; Parras, F; Suárez, M; Rodés, A; Noguer, I

2003-12-15

In Spain, approximately 10 years passed between the time when human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) harm-reduction programs should have been developed with sufficient coverage to have an optimum impact on public health (before the HIV/AIDS epidemic's explosion in 1984) and the date of their actual implementation. This delay yielded an enormous cost for the country. The introduction of the virus in drug injector networks during a period of widespread diffusion of heroin injection and the lack of political awareness of the growing problem were 2 important factors that contributed to the important diffusion of the HIV infection among Spanish injection drug users. Lessons can be learned that may be of great interest in countries or territories facing similar challenges now and in the future.

Convergence to a pulsating travelling wave for an epidemic reaction-diffusion system with non-diffusive susceptible population.

PubMed

Ducrot, Arnaud; Giletti, Thomas

2014-09-01

In this work we study the asymptotic behaviour of the Kermack-McKendrick reaction-diffusion system in a periodic environment with non-diffusive susceptible population. This problem was proposed by Kallen et al. as a model for the spatial spread for epidemics, where it can be reasonable to assume that the susceptible population is motionless. For arbitrary dimensional space we prove that large classes of solutions of such a system have an asymptotic spreading speed in large time, and that the infected population has some pulse-like asymptotic shape. The analysis of the one-dimensional problem is more developed, as we are able to uncover a much more accurate description of the profile of solutions. Indeed, we will see that, for some initially compactly supported infected population, the profile of the solution converges to some pulsating travelling wave with minimal speed, that is to some entire solution moving at a constant positive speed and whose profile's shape is periodic in time.

Random walks exhibiting anomalous diffusion: elephants, urns and the limits of normality

NASA Astrophysics Data System (ADS)

Kearney, Michael J.; Martin, Richard J.

2018-01-01

A random walk model is presented which exhibits a transition from standard to anomalous diffusion as a parameter is varied. The model is a variant on the elephant random walk and differs in respect of the treatment of the initial state, which in the present work consists of a given number N of fixed steps. This also links the elephant random walk to other types of history dependent random walk. As well as being amenable to direct analysis, the model is shown to be asymptotically equivalent to a non-linear urn process. This provides fresh insights into the limiting form of the distribution of the walker’s position at large times. Although the distribution is intrinsically non-Gaussian in the anomalous diffusion regime, it gradually reverts to normal form when N is large under quite general conditions.

Automated Analysis of siRNA Screens of Virus Infected Cells Based on Immunofluorescence Microscopy

NASA Astrophysics Data System (ADS)

Matula, Petr; Kumar, Anil; Wörz, Ilka; Harder, Nathalie; Erfle, Holger; Bartenschlager, Ralf; Eils, Roland; Rohr, Karl

We present an image analysis approach as part of a high-throughput microscopy screening system based on cell arrays for the identification of genes involved in Hepatitis C and Dengue virus replication. Our approach comprises: cell nucleus segmentation, quantification of virus replication level in cells, localization of regions with transfected cells, cell classification by infection status, and quality assessment of an experiment. The approach is fully automatic and has been successfully applied to a large number of cell array images from screening experiments. The experimental results show a good agreement with the expected behavior of positive as well as negative controls and encourage the application to screens from further high-throughput experiments.

Temporal variation in viral hemorrhagic septicemia virus antibodies in freshwater drum (Aplodinotus grunniens) indicates cyclic transmission in Lake Winnebago, Wisconsin

USGS Publications Warehouse

Wilson-Rothering, Anna; Marcquenski, Susan; Koenigs, Ryan P.; Bruch, Ronald; Kamke, Kendall; Isermann, Daniel A.; Thurman, Andrew; Toohey-Kurth, Kathy; Goldberg, Tony

2015-01-01

Viral hemorrhagic septicemia virus (VHSV) is an emerging pathogen that causes mass mortality in multiple fish species. In 2007, the Great Lakes freshwater strain, type IVb, caused a large die-off of freshwater drum (Aplodinotus grunniens) in Lake Winnebago, Wisconsin, USA. To evaluate the persistence and transmission of VHSV, freshwater drum from Lake Winnebago were tested for antibodies to the virus using recently developed virus neutralization (VN) and enzyme-linked immunosorbent (ELISA) assays. Samples were also tested by real-time reverse transcription-PCR (rRT-PCR) to detect viral RNA. Of 548 serum samples tested, 44 (8.03%) were positive by VN (titers ranging from 1:16 to 1:1,024) and 45 (8.21%) were positive by ELISA, including 7 fish positive by both assays. Antibody prevalence increased with age and was higher in one northwestern area of Lake Winnebago than in other areas. Of 3,864 tissues sampled from 551 fish, 1 spleen and 1 kidney sample from a single adult female fish collected in the spring of 2012 tested positive for VHSV by rRT-PCR, and serum from the same fish tested positive by VN and ELISA. These results suggest that VHSV persists and viral transmission may be active in Lake Winnebago even in years following outbreaks and that wild fish may survive VHSV infection and maintain detectable antibody titers while harboring viral RNA. Influxes of immunologically naive juvenile fish through recruitment may reduce herd immunity, allow VHSV to persist, and drive superannual cycles of transmission that may sporadically manifest as fish kills.

Temporal Variation in Viral Hemorrhagic Septicemia Virus Antibodies in Freshwater Drum (Aplodinotus grunniens) Indicates Cyclic Transmission in Lake Winnebago, Wisconsin

PubMed Central

Wilson-Rothering, Anna; Marcquenski, Susan; Koenigs, Ryan; Bruch, Ronald; Kamke, Kendall; Isermann, Daniel; Thurman, Andrew; Toohey-Kurth, Kathy

2015-01-01

Viral hemorrhagic septicemia virus (VHSV) is an emerging pathogen that causes mass mortality in multiple fish species. In 2007, the Great Lakes freshwater strain, type IVb, caused a large die-off of freshwater drum (Aplodinotus grunniens) in Lake Winnebago, Wisconsin, USA. To evaluate the persistence and transmission of VHSV, freshwater drum from Lake Winnebago were tested for antibodies to the virus using recently developed virus neutralization (VN) and enzyme-linked immunosorbent (ELISA) assays. Samples were also tested by real-time reverse transcription-PCR (rRT-PCR) to detect viral RNA. Of 548 serum samples tested, 44 (8.03%) were positive by VN (titers ranging from 1:16 to 1:1,024) and 45 (8.21%) were positive by ELISA, including 7 fish positive by both assays. Antibody prevalence increased with age and was higher in one northwestern area of Lake Winnebago than in other areas. Of 3,864 tissues sampled from 551 fish, 1 spleen and 1 kidney sample from a single adult female fish collected in the spring of 2012 tested positive for VHSV by rRT-PCR, and serum from the same fish tested positive by VN and ELISA. These results suggest that VHSV persists and viral transmission may be active in Lake Winnebago even in years following outbreaks and that wild fish may survive VHSV infection and maintain detectable antibody titers while harboring viral RNA. Influxes of immunologically naive juvenile fish through recruitment may reduce herd immunity, allow VHSV to persist, and drive superannual cycles of transmission that may sporadically manifest as fish kills. PMID:26135873

Plasma Epstein-Barr virus and Hepatitis B virus in non-Hodgkin lymphomas: Two lymphotropic, potentially oncogenic, latently occurring DNA viruses.

PubMed

Sinha, Mahua; Rao, Clementina Rama; Premalata, C S; Shafiulla, Mohammed; Lakshmaiah, K C; Jacob, Linu Abraham; Babu, Govind K; Viveka, B K; Appaji, L; Subramanyam, Jayshree R

2016-01-01

There is a need to study potential infective etiologies in lymphomas. Lymphocyte-transforming viruses can directly infect lymphocytes, disrupt normal cell functions, and promote cell division. Epstein-Barr virus (EBV) is known to be associated with several lymphomas, especially Hodgkin lymphomas (HLs). And recently, the lymphocyte-transforming role of hepatitis B virus (HBV) has been emphasized. The aim of this study was to elucidate the association of two potentially oncogenic, widely prevalent latent DNA viruses, EBV and HBV, in non-HL (NHL). In this prospective study, we estimated plasma EBV and HBV DNA in NHL patients. Peripheral blood was obtained from newly diagnosed, treatment na ïve, histologically confirmed NHL patients. Plasma EBV DNA was quantified by real-time polymerase chain reaction (PCR) targeting Epstein-Barr Nucleic acid 1 while the plasma HBV DNA was detected using nested PCR targeting HBX gene. In a small subset of patients, follow-up plasma samples post-anticancer chemotherapy were available and retested for viral DNA. Of the 110 NHL patients, ~79% were B-cell NHL and ~21% were T-cell NHL. Plasma EBV-DNA was detected in 10% NHLs with a higher EBV association in Burkitt lymphoma (33.3%) than other subtypes. Pretherapy HBV DNA was detected in 21% NHLs; most of them being diffuse large B-cell lymphoma (DLBCL). Moreover, 42% of DLBCL patients had HBV DNA in plasma. Since all patients were HBV surface antigen seronegative at diagnosis, baseline plasma HBV-DNAemia before chemotherapy was indicative of occult hepatitis B infection. Our findings indicate a significant association of HBV with newly diagnosed DLBCL.

Carfilzomib, Rituximab, and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2018-05-16

Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

A 4-year study of avian influenza virus prevalence and subtype diversity in ducks of Newfoundland, Canada.

PubMed

Huang, Yanyan; Wille, Michelle; Dobbin, Ashley; Robertson, Gregory J; Ryan, Pierre; Ojkic, Davor; Whitney, Hugh; Lang, Andrew S

2013-10-01

The island of Newfoundland, Canada, is at the eastern edge of North America and has migratory bird connections with the continental mainland as well as across the North Atlantic Ocean. Here, we report a 4-year avian influenza virus (AIV) epidemiological study in ducks in the St. John's region of Newfoundland. The overall prevalence of AIV detection in ducks during this study was 7.2%, with American Black Ducks contributing the vast majority of the collected samples and the AIV positives. The juvenile ducks showed a significantly higher AIV detection rate (10.6%) compared with adults (3.4%). Seasonally, AIV prevalence rates were higher in the autumn (8.4%), but positives were still detected in the winter (4.6%). Preliminary serology tests showed a high incidence of previous AIV infection (20/38, 52.6%). A total of 43 viruses were characterized for their HA-NA or HA subtypes, which revealed a large diversity of AIV subtypes and little recurrence of subtypes from year to year. Investigation of the movement patterns of ducks in this region showed that it is a largely non-migratory duck population, which may contribute to the observed pattern of high AIV subtype turnover. Phylogenetic analysis of 4 H1N1 and one H5N4 AIVs showed these viruses were highly similar to other low pathogenic AIV sequences from waterfowl in North America and assigned all gene segments into American-avian clades. Notably, the H1N1 viruses, which were identified in consecutive years, possessed homologous genomes. Such detection of homologous AIV genomes across years is rare, but indicates the role of the environmental reservoir in viral perpetuation.

Accelerated appearance of multiple B cell lymphoma types in NFS/N mice congenic for ecotropic murine leukemia viruses.

PubMed

Hartley, J W; Chattopadhyay, S K; Lander, M R; Taddesse-Heath, L; Naghashfar, Z; Morse, H C; Fredrickson, T N

2000-02-01

Spontaneous lymphomas occur at high frequency in NFS x V+ mice, strains congenic for ecotropic murine leukemia virus (MuLV) proviral genes and expressing virus at high titer. In the present study, a total of 703 NFS x V+ lymphomas were studied by histopathology, immunophenotypic analysis, immunoglobulin heavy chain or T cell receptor beta chain rearrangements, and somatic ecotropic MuLV integrations; 90% of the lymphomas tested were of B cell lineage. Low-grade tumors included small lymphocytic, follicular, and splenic marginal zone lymphomas, while high-grade tumors comprised diffuse large-cell (centroblastic and immunoblastic types), splenic marginal zone, and lymphoblastic lymphomas. Comparison of mice of similar genetic background except for presence (NFS x V+) or absence (NFS x V-) of functional ecotropic MuLV genomes showed that NFS x V-clonal lymphomas developed at about one-half the rate of those occurring in NFS x V+ mice, and most were low-grade B cell lymphomas with extended latent periods. In NFS x V+ mice, clonal outgrowth, defined by Ig gene rearrangements, was associated with acquisition of somatic ecotropic proviral integrations, suggesting that, although generation of B cell clones can be virus independent, ecotropic virus may act to increase the rate of generation of clones and speed their evolution to lymphoma. The mechanism remains undefined, because only rare rearrangements were detected in several cellular loci previously associated with MuLV insertional mutagenesis.

Rift Valley fever virus MP-12 vaccine encoding Toscana virus NSs retains neuroinvasiveness in mice.

PubMed

Indran, Sabarish V; Lihoradova, Olga A; Phoenix, Inaia; Lokugamage, Nandadeva; Kalveram, Birte; Head, Jennifer A; Tigabu, Bersabeh; Smith, Jennifer K; Zhang, Lihong; Juelich, Terry L; Gong, Bin; Freiberg, Alexander N; Ikegami, Tetsuro

2013-07-01

Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12-TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-β gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV.

Rift Valley fever virus MP-12 vaccine encoding Toscana virus NSs retains neuroinvasiveness in mice

PubMed Central

Indran, Sabarish V.; Lihoradova, Olga A.; Phoenix, Inaia; Lokugamage, Nandadeva; Kalveram, Birte; Head, Jennifer A.; Tigabu, Bersabeh; Smith, Jennifer K.; Zhang, Lihong; Juelich, Terry L.; Gong, Bin; Freiberg, Alexander N.

2013-01-01

Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12-TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-β gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV. PMID:23515022

A Hierarchical Network Approach for Modeling Rift Valley Fever Epidemics with Applications in North America

PubMed Central

Xue, Ling; Cohnstaedt, Lee W.; Scott, H. Morgan; Scoglio, Caterina

2013-01-01

Rift Valley fever is a vector-borne zoonotic disease which causes high morbidity and mortality in livestock. In the event Rift Valley fever virus is introduced to the United States or other non-endemic areas, understanding the potential patterns of spread and the areas at risk based on disease vectors and hosts will be vital for developing mitigation strategies. Presented here is a general network-based mathematical model of Rift Valley fever. Given a lack of empirical data on disease vector species and their vector competence, this discrete time epidemic model uses stochastic parameters following several PERT distributions to model the dynamic interactions between hosts and likely North American mosquito vectors in dispersed geographic areas. Spatial effects and climate factors are also addressed in the model. The model is applied to a large directed asymmetric network of 3,621 nodes based on actual farms to examine a hypothetical introduction to some counties of Texas, an important ranching area in the United States of America. The nodes of the networks represent livestock farms, livestock markets, and feedlots, and the links represent cattle movements and mosquito diffusion between different nodes. Cattle and mosquito (Aedes and Culex) populations are treated with different contact networks to assess virus propagation. Rift Valley fever virus spread is assessed under various initial infection conditions (infected mosquito eggs, adults or cattle). A surprising trend is fewer initial infectious organisms result in a longer delay before a larger and more prolonged outbreak. The delay is likely caused by a lack of herd immunity while the infection expands geographically before becoming an epidemic involving many dispersed farms and animals almost simultaneously. Cattle movement between farms is a large driver of virus expansion, thus quarantines can be efficient mitigation strategy to prevent further geographic spread. PMID:23667453

A hierarchical network approach for modeling Rift Valley fever epidemics with applications in North America.

PubMed

Xue, Ling; Cohnstaedt, Lee W; Scott, H Morgan; Scoglio, Caterina

2013-01-01

Rift Valley fever is a vector-borne zoonotic disease which causes high morbidity and mortality in livestock. In the event Rift Valley fever virus is introduced to the United States or other non-endemic areas, understanding the potential patterns of spread and the areas at risk based on disease vectors and hosts will be vital for developing mitigation strategies. Presented here is a general network-based mathematical model of Rift Valley fever. Given a lack of empirical data on disease vector species and their vector competence, this discrete time epidemic model uses stochastic parameters following several PERT distributions to model the dynamic interactions between hosts and likely North American mosquito vectors in dispersed geographic areas. Spatial effects and climate factors are also addressed in the model. The model is applied to a large directed asymmetric network of 3,621 nodes based on actual farms to examine a hypothetical introduction to some counties of Texas, an important ranching area in the United States of America. The nodes of the networks represent livestock farms, livestock markets, and feedlots, and the links represent cattle movements and mosquito diffusion between different nodes. Cattle and mosquito (Aedes and Culex) populations are treated with different contact networks to assess virus propagation. Rift Valley fever virus spread is assessed under various initial infection conditions (infected mosquito eggs, adults or cattle). A surprising trend is fewer initial infectious organisms result in a longer delay before a larger and more prolonged outbreak. The delay is likely caused by a lack of herd immunity while the infection expands geographically before becoming an epidemic involving many dispersed farms and animals almost simultaneously. Cattle movement between farms is a large driver of virus expansion, thus quarantines can be efficient mitigation strategy to prevent further geographic spread.

Tripartite differentiation (squamous, glandular, and melanocytic) of a primary cutaneous neuroendocrine carcinoma. An immunocytochemical and ultrastructural study.

PubMed

Isimbaldi, G; Sironi, M; Taccagni, G; Declich, P; Dell'Antonio, A; Galli, C

1993-06-01

We report a case of primary cutaneous neuroendocrine carcinoma (PCNEC) with squamous, glandular, and melanocytic differentiation and associated Bowen disease. The paranuclear globular positivity of low-molecular-weight cytokeratins agrees with the ultrastructural observations of paranuclear fibrous bodies in the small neuroendocrine cells, while the diffuse cytoplasmic positivity corresponds to the sparse intermediate filaments in large cells with squamous differentiation. "Transitional forms" are characterized by both diffuse and globular cytoplasmic positivity for cytokeratins and by the ultrastructural evidence of neuroendocrine and squamous features. Therefore the ultrastructural demonstration of intracytoplasmic tonofibrils and tonofilaments, intercellular glandular lumina, lined by well-formed microvilli, and immature premelanosomes in the neurosecretory cells supports the proposed tripartite differentiation of neuroendocrine cells of this case of PCNEC.

Delayed Temporal Lobe Hemorrhage After Initiation of Acyclovir in an Immunocompetent Patient with Herpes Simplex Virus-2 Encephalitis: A Case Report.

PubMed

Mueller, Kyle; Ryan, Joshua E; Tai, Alex; Armonda, Rocco A

2017-01-15

Herpes simplex virus (HSV) is the most common cause of non-epidemic, sporadic, acute focal encephalitis in the United States. Inflammation of the vasculature makes them friable and susceptible to hemorrhage. Massive hemorrhage, though rare, can present in a delayed fashion after initiation of acyclovir and often requires surgical intervention. We report a unique case of delayed temporal lobe hemorrhage after initiation of acyclovir in an immunocompetent patient, specifically for its presentation, virology, and surgical management. A 40-year-old left-handed Caucasian female with chronic headaches, along with a 20-pack-year smoking history, presented to an outside facility with one week of diffuse, generalized headache, fever, nausea, and vomiting. Initial cranial imaging was negative for hemorrhage. Cerebrospinal fluid (CSF) studies showed a lymphocytic pleocytosis with elevated protein, along with polymerase chain reaction (PCR) positive staining for HSV, establishing the diagnosis of HSV-2 encephalitis, which is less common in adults. Acyclovir was initiated and one week later while still hospitalized, the patient developed acute altered mental status with cranial imaging showing a large right temporal lobe hemorrhage with significant midline shift. She was transferred to our facility for surgical intervention. Computed tomography angiography (CTA) was negative for any underlying vascular lesion. She was taken to the operating room for a decompressive unilateral (right) hemicraniectomy and temporal lobectomy. She had no postoperative complications and completed a three-week course of acyclovir. She was discharged to acute rehab with plans to return at a later date for cranioplasty. Intracerebral hemorrhage is an uncommon, although possible sequela, of herpes encephalitis. Despite initiation of early antiviral therapy, close monitoring is warranted, given the pathophysiology of the vasculature. Any decline in the neurological exam and/or increasing symptomatology of increased intracranial pressure mandates immediate cranial imaging to evaluate for possible hemorrhage. Emergent surgical intervention is warranted with large temporal lobe hemorrhages.

Two separable functional domains of simian virus 40 large T antigen: carboxyl-terminal region of simian virus 40 large T antigen is required for efficient capsid protein synthesis.

PubMed Central

Tornow, J; Polvino-Bodnar, M; Santangelo, G; Cole, C N

1985-01-01

The carboxyl-terminal portion of simian virus 40 large T antigen is essential for productive infection of CV-1 and CV-1p green monkey kidney cells. Mutant dlA2459, lacking 14 base pairs at 0.193 map units, was positive for viral DNA replication, but unable to form plaques in CV-1p cells (J. Tornow and C.N. Cole, J. Virol. 47:487-494, 1983). In this report, the defect of dlA2459 is further defined. Simian virus 40 late mRNAs were transcribed, polyadenylated, spliced, and transported in dlA2459-infected cells, but the level of capsid proteins produced in infected CV-1 green monkey kidney cells was extremely low. dlA2459 large T antigen lacks those residues known to be required for adenovirus helper function, and the block to productive infection by dlA2459 occurs at the same stage of infection as the block to productive adenovirus infection of CV-1 cells. These results suggest that the adenovirus helper function is required for productive infection by simian virus 40. Mutant dlA2459 was able to grow on the Vero and BSC-1 lines of African green monkey kidney cells. Additional mutants affecting the carboxyl-terminal portion of large T were prepared. Mutant inv2408 contains an inversion of the DNA between the BamHI and BclI sites (0.144 to 0.189 map units). This inversion causes transposition of the carboxyl-terminal 26 amino acids of large T antigen and the carboxyl-terminal 18 amino acids of VP1. This mutant was viable, even though the essential information absent from dlA2459 large T antigen has been transferred to the carboxyl terminus of VP1 of inv2408. The VP1 polypeptide carrying this carboxyl-terminal portion of large T could overcome the defect of dlA2459. This indicates that the carboxyl terminus of large T antigen is a separate and separable functional domain. Images PMID:2982029

Crystallization and preliminary X-ray diffraction analysis of West Nile virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaufmann, Barbel; Plevka, Pavel; Kuhn, Richard J.

2010-05-25

West Nile virus, a human pathogen, is closely related to other medically important flaviviruses of global impact such as dengue virus. The infectious virus was purified from cell culture using polyethylene glycol (PEG) precipitation and density-gradient centrifugation. Thin amorphously shaped crystals of the lipid-enveloped virus were grown in quartz capillaries equilibrated by vapor diffusion. Crystal diffraction extended at best to a resolution of about 25 {angstrom} using synchrotron radiation. A preliminary analysis of the diffraction images indicated that the crystals had unit-cell parameters a {approx_equal} b {approx_equal} 480 {angstrom}, {gamma} = 120{sup o}, suggesting a tight hexagonal packing of onemore » virus particle per unit cell.« less

Epstein-Barr Virus in Gastric Carcinoma

PubMed Central

Nishikawa, Jun; Yoshiyama, Hironori; Iizasa, Hisashi; Kanehiro, Yuichi; Nakamura, Munetaka; Nishimura, Junichi; Saito, Mari; Okamoto, Takeshi; Sakai, Kouhei; Suehiro, Yutaka; Yamasaki, Takahiro; Oga, Atsunori; Yanai, Hideo; Sakaida, Isao

2014-01-01

The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma, all tumor cells harbor the clonal EBV genome. Gastric carcinoma associated with EBV has distinct clinicopathological features, occurs predominately in men and in younger-aged individuals, and presents a generally diffuse histological type. Most cases of EBV-associated gastric carcinoma exhibit a histology rich in lymphocyte infiltration. The immunological reactiveness in the host may represent a relatively preferable prognosis in EBV-positive cases. This fact highlights the important role of EBV in the development of EBV-associated gastric carcinoma. We have clearly proved direct infection of human gastric epithelialcells by EBV. The infection was achieved by using a recombinant EBV. Promotion of growth by EBV infection was observed in the cells. Considerable data suggest that EBV may directly contribute to the development of EBV-associated GC. This tumor-promoting effect seems to involve multiple mechanisms, because EBV affects several host proteins and pathways that normally promote apoptosis and regulate cell proliferation. PMID:25386788

Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated High- or High-Intermediate-Risk Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2016-03-01

Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

Novel approach for identification of influenza virus host range and zoonotic transmissible sequences by determination of host-related associative positions in viral genome segments.

PubMed

Kargarfard, Fatemeh; Sami, Ashkan; Mohammadi-Dehcheshmeh, Manijeh; Ebrahimie, Esmaeil

2016-11-16

Recent (2013 and 2009) zoonotic transmission of avian or porcine influenza to humans highlights an increase in host range by evading species barriers. Gene reassortment or antigenic shift between viruses from two or more hosts can generate a new life-threatening virus when the new shuffled virus is no longer recognized by antibodies existing within human populations. There is no large scale study to help understand the underlying mechanisms of host transmission. Furthermore, there is no clear understanding of how different segments of the influenza genome contribute in the final determination of host range. To obtain insight into the rules underpinning host range determination, various supervised machine learning algorithms were employed to mine reassortment changes in different viral segments in a range of hosts. Our multi-host dataset contained whole segments of 674 influenza strains organized into three host categories: avian, human, and swine. Some of the sequences were assigned to multiple hosts. In point of fact, the datasets are a form of multi-labeled dataset and we utilized a multi-label learning method to identify discriminative sequence sites. Then algorithms such as CBA, Ripper, and decision tree were applied to extract informative and descriptive association rules for each viral protein segment. We found informative rules in all segments that are common within the same host class but varied between different hosts. For example, for infection of an avian host, HA14V and NS1230S were the most important discriminative and combinatorial positions. Host range identification is facilitated by high support combined rules in this study. Our major goal was to detect discriminative genomic positions that were able to identify multi host viruses, because such viruses are likely to cause pandemic or disastrous epidemics.

Capsid coding region diversity of re-emerging lineage C foot-and-mouth disease virus serotype Asia1 from India.

PubMed

Subramaniam, Saravanan; Mohapatra, Jajati K; Das, Biswajit; Sharma, Gaurav K; Biswal, Jitendra K; Mahajan, Sonalika; Misri, Jyoti; Dash, Bana B; Pattnaik, Bramhadev

2015-07-01

Foot-and-mouth disease virus (FMDV) serotype Asia1 was first reported in India in 1951, where three major genetic lineages (B, C and D) of this serotype have been described until now. In this study, the capsid protein coding region of serotype Asia1 viruses (n = 99) from India were analyzed, giving importance to the viruses circulating since 2007. All of the isolates (n = 50) recovered during 2007-2013 were found to group within the re-emerging cluster of lineage C (designated as sublineage C(R)). The evolutionary rate of sublineage C(R) was estimated to be slightly higher than that of the serotype as a whole, and the time of the most recent common ancestor for this cluster was estimated to be approximately 2001. In comparison to the older isolates of lineage C (1993-2001), the re-emerging viruses showed variation at eight amino acid positions, including substitutions at the antigenically critical residues VP279 and VP2131. However, no direct correlation was found between sequence variations and antigenic relationships. The number of codons under positive selection and the nature of the selection pressure varied widely among the structural proteins, implying a heterogeneous pattern of evolution in serotype Asia1. While episodic diversifying selection appears to play a major role in shaping the evolution of VP1 and VP3, selection pressure acting on codons of VP2 is largely pervasive. Further, episodic positive selection appears to be responsible for the early diversification of lineage C. Recombination events identified in the structural protein coding region indicates its probable role in adaptive evolution of serotype Asia1 viruses.

The number of genes encoding repeat domain-containing proteins positively correlates with genome size in amoebal giant viruses

PubMed Central

Shukla, Avi; Chatterjee, Anirvan

2018-01-01

Abstract Curiously, in viruses, the virion volume appears to be predominantly driven by genome length rather than the number of proteins it encodes or geometric constraints. With their large genome and giant particle size, amoebal viruses (AVs) are ideally suited to study the relationship between genome and virion size and explore the role of genome plasticity in their evolutionary success. Different genomic regions of AVs exhibit distinct genealogies. Although the vertically transferred core genes and their functions are universally conserved across the nucleocytoplasmic large DNA virus (NCLDV) families and are essential for their replication, the horizontally acquired genes are variable across families and are lineage-specific. When compared with other giant virus families, we observed a near–linear increase in the number of genes encoding repeat domain-containing proteins (RDCPs) with the increase in the genome size of AVs. From what is known about the functions of RDCPs in bacteria and eukaryotes and their prevalence in the AV genomes, we envisage important roles for RDCPs in the life cycle of AVs, their genome expansion, and plasticity. This observation also supports the evolution of AVs from a smaller viral ancestor by the acquisition of diverse gene families from the environment including RDCPs that might have helped in host adaption. PMID:29308275

Pneumopathie interstitielle diffuse révélant la leucémie-lymphome à cellules T de l’adulte HTLV1+

PubMed Central

Bouanani, Nouama; Lamchahab, Mouna

2016-01-01

La leucémie/lymphome à cellules T de l'adulte est une prolifération tumorale de cellules lymphoïdes T matures activées, dont l'agent étiologique est le rétrovirus humain T cell-leukemia virus type 1, ce virus entraine rarement des désordres inflammatoires bronchioloalveolaires. Nous rapportons l'observation d'un patient hospitalisé pour une pneumopathie interstitielle diffuse et dont le bilan étiologique a révélé une leucémie lymphome à cellules T de l'adulte HTLV1+. PMID:28292112

Waterborne Viruses and F-Specific Coliphages in Mixed-Use Watersheds: Microbial Associations, Host Specificities, and Affinities with Environmental/Land Use Factors

PubMed Central

Jones, Tineke H.; Brassard, Julie; Topp, Edward; Wilkes, Graham

2016-01-01

ABSTRACT From the years 2008 to 2014, a total of 1,155 water samples were collected (spring to fall) from 24 surface water sampling sites located in a mixed-used but predominantly agricultural (i.e., dairy livestock production) river basin in eastern Ontario, Canada. Water was analyzed for viable F-specific DNA (F-DNA) and F-specific RNA (F-RNA) (genogroup I [GI] to GIV) coliphage and a suite of molecularly detected viruses (norovirus [GI to GIV], torque teno virus [TTV], rotavirus, kobuvirus, adenovirus, astrovirus, hepatitis A, and hepatitis E). F-DNA and F-RNA coliphage were detected in 33 and 28% of the samples at maximum concentrations of 2,000 and 16,300 PFU · 100 ml−1, respectively. Animal TTV, human TTV, kobuvirus, astrovirus, and norovirus GIII were the most prevalent viruses, found in 23, 20, 13, 12, and 11% of samples, respectively. Viable F-DNA coliphage was found to be a modest positive indicator of molecularly detected TTV. F-RNA coliphage, unlike F-DNA coliphage, was a modest positive predictor of norovirus and rotavirus. There were, however, a number of significant negative associations among F-specific coliphage and viruses. F-DNA coliphage densities of >142 PFU · 100 ml−1 delineated conditions when ∼95% of water samples contained some type of virus. Kobuvirus was the virus most strongly related to detection of any other virus. Land use had some associations with virus/F-specific coliphage detection, but season and surface water flow were the variables that were most important for broadly delineating detection. Higher relative levels of detection of human viruses and human F-RNA coliphage were associated with higher relative degrees of upstream human land development in a catchment. IMPORTANCE This study is one of the first, to our knowledge, to evaluate relationships among F-specific coliphages and a large suite of enteric viruses in mixed-use but agriculturally dominated surface waters in Canada. This study suggested that relationships between viable F-specific coliphages and molecularly detected viruses do exist, but they are not always positive. Caution should be employed if viable F-specific coliphages are to be used as indicators of virus presence in surface waters. This study elucidates relative effects of agriculture, wildlife, and human activity on virus and F-specific coliphage detection. Seasonal and meteorological attributes play a strong role in the detection of most virus and F-specific coliphage targets. PMID:27836843

Waterborne Viruses and F-Specific Coliphages in Mixed-Use Watersheds: Microbial Associations, Host Specificities, and Affinities with Environmental/Land Use Factors.

PubMed

Jones, Tineke H; Brassard, Julie; Topp, Edward; Wilkes, Graham; Lapen, David R

2017-02-01

From the years 2008 to 2014, a total of 1,155 water samples were collected (spring to fall) from 24 surface water sampling sites located in a mixed-used but predominantly agricultural (i.e., dairy livestock production) river basin in eastern Ontario, Canada. Water was analyzed for viable F-specific DNA (F-DNA) and F-specific RNA (F-RNA) (genogroup I [GI] to GIV) coliphage and a suite of molecularly detected viruses (norovirus [GI to GIV], torque teno virus [TTV], rotavirus, kobuvirus, adenovirus, astrovirus, hepatitis A, and hepatitis E). F-DNA and F-RNA coliphage were detected in 33 and 28% of the samples at maximum concentrations of 2,000 and 16,300 PFU · 100 ml -1 , respectively. Animal TTV, human TTV, kobuvirus, astrovirus, and norovirus GIII were the most prevalent viruses, found in 23, 20, 13, 12, and 11% of samples, respectively. Viable F-DNA coliphage was found to be a modest positive indicator of molecularly detected TTV. F-RNA coliphage, unlike F-DNA coliphage, was a modest positive predictor of norovirus and rotavirus. There were, however, a number of significant negative associations among F-specific coliphage and viruses. F-DNA coliphage densities of >142 PFU · 100 ml -1 delineated conditions when ∼95% of water samples contained some type of virus. Kobuvirus was the virus most strongly related to detection of any other virus. Land use had some associations with virus/F-specific coliphage detection, but season and surface water flow were the variables that were most important for broadly delineating detection. Higher relative levels of detection of human viruses and human F-RNA coliphage were associated with higher relative degrees of upstream human land development in a catchment. This study is one of the first, to our knowledge, to evaluate relationships among F-specific coliphages and a large suite of enteric viruses in mixed-use but agriculturally dominated surface waters in Canada. This study suggested that relationships between viable F-specific coliphages and molecularly detected viruses do exist, but they are not always positive. Caution should be employed if viable F-specific coliphages are to be used as indicators of virus presence in surface waters. This study elucidates relative effects of agriculture, wildlife, and human activity on virus and F-specific coliphage detection. Seasonal and meteorological attributes play a strong role in the detection of most virus and F-specific coliphage targets. © Crown copyright 2017.

Replication of tobacco mosaic virus RNA.

PubMed Central

Buck, K W

1999-01-01

The replication of tobacco mosaic virus (TMV) RNA involves synthesis of a negative-strand RNA using the genomic positive-strand RNA as a template, followed by the synthesis of positive-strand RNA on the negative-strand RNA templates. Intermediates of replication isolated from infected cells include completely double-stranded RNA (replicative form) and partly double-stranded and partly single-stranded RNA (replicative intermediate), but it is not known whether these structures are double-stranded or largely single-stranded in vivo. The synthesis of negative strands ceases before that of positive strands, and positive and negative strands may be synthesized by two different polymerases. The genomic-length negative strand also serves as a template for the synthesis of subgenomic mRNAs for the virus movement and coat proteins. Both the virus-encoded 126-kDa protein, which has amino-acid sequence motifs typical of methyltransferases and helicases, and the 183-kDa protein, which has additional motifs characteristic of RNA-dependent RNA polymerases, are required for efficient TMV RNA replication. Purified TMV RNA polymerase also contains a host protein serologically related to the RNA-binding subunit of the yeast translational initiation factor, eIF3. Study of Arabidopsis mutants defective in RNA replication indicates that at least two host proteins are needed for TMV RNA replication. The tomato resistance gene Tm-1 may also encode a mutant form of a host protein component of the TMV replicase. TMV replicase complexes are located on the endoplasmic reticulum in close association with the cytoskeleton in cytoplasmic bodies called viroplasms, which mature to produce 'X bodies'. Viroplasms are sites of both RNA replication and protein synthesis, and may provide compartments in which the various stages of the virus mutiplication cycle (protein synthesis, RNA replication, virus movement, encapsidation) are localized and coordinated. Membranes may also be important for the configuration of the replicase with respect to initiation of RNA synthesis, and synthesis and release of progeny single-stranded RNA. PMID:10212941

Factors Influencing Virulence and Plaque Properties of Attenuated Venezuelan Equine Encephalomyelitis Virus Populations

PubMed Central

Hearn, Henry J.; Seliokas, Zenonas V.; Andersen, Arthur A.

1969-01-01

A minority of stable large-plaque virus increased proportionally in stored unstable attenuated (9t) Venezuelan equine encephalomyelitis virus populations. L-cell-grown progeny (9t2) of stored 9t showed large amounts of large-plaque virus and increased virulence. Small-plaque virus inhibited large-plaque virus but not the reverse. Serial passage of small-plaque virus from 9t2 yielded a strain (20t) that was more attenuated than 9t. PMID:5823235

Ulcerative cheilitis in a rhesus macaque.

PubMed

Bailey, C C; Miller, A D

2012-03-01

A 2-year-old, female, simian immunodeficiency virus E543-infected rhesus macaque (Macaca mulatta) was presented for necropsy following euthanasia due to a history of diarrhea, weight loss, and a small, round ulcer along the left labial commissure. Histopathologic examination of the ulcer revealed infiltration by large numbers of degenerate and nondegenerate neutrophils and macrophages admixed with syncytial epithelial cells. Rare epithelial cells contained herpetic inclusion bodies. These cells stained positive for Human herpesvirus 1 via immunohistochemistry, and DNA sequencing confirmed the presence of closely related Macacine herpesvirus 1 (B virus).

Ulcerative Cheilitis in a Rhesus Macaque

PubMed Central

Bailey, C. C.; Miller, A. D.

2011-01-01

A two-year-old, female, simian immunodeficiency virus E543-infected rhesus macaque (Macaca mulatta) was presented for necropsy following euthanasia due to a history of diarrhea, weight loss, and a small, round ulcer along the left labial commisure. Histopathologic examination of the ulcer revealed infiltration by large numbers of degenerate and non-degenerate neutrophils and macrophages admixed with syncytial epithelial cells. Rare epithelial cells contained herpetic inclusion bodies. These cells stained positive for Human herpesvirus 1 via immunohistochemistry and DNA sequencing confirmed the presence of closely related Macacine herpesvirus 1 (B virus). PMID:21383117

Serological detection systems for identification of cows shedding bovine foamy virus via milk.

PubMed

Romen, Fabian; Backes, Perdita; Materniak, Magda; Sting, Reinhard; Vahlenkamp, Thomas W; Riebe, Roland; Pawlita, Michael; Kuzmak, Jacek; Löchelt, Martin

2007-07-20

The biology of foamy viruses, their mode of transmission and disease potential in their natural host and after interspecies transmission are largely unknown. To gain insights into the prevalence of bovine foamy virus (BFV) and its zoonotic potential, enzyme-linked immunosorbent assays (ELISAs) were established to determine antibody responses against Gag, Env, and the non-structural protein Bet in bovine serum and milk. In Polish cattle, strong Gag reactivity was most frequent (41.5%) and strongly associated with Bet antibodies, Env antibodies were less frequent. German cattle showed a low overall BFV antibody prevalence of 6.8%. Besides clearly BFV-positive animals, a substantial number of weakly reacting cattle were identified. BFV-specific antibodies were also detectable in milk. BFV was isolated from PBLs and milk cells of BFV-positive cattle but not from antibody-negative or weakly reacting animals. The implications of these findings for the potential interspecies transmission of BFV to humans will be discussed.

Oblimersen Sodium and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage I, Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2012-10-11

Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

Serial femtosecond X-ray diffraction of enveloped virus microcrystals

DOE PAGES

Lawrence, Robert M.; Conrad, Chelsie E.; Zatsepin, Nadia A.; ...

2015-08-20

Serial femtosecond crystallography (SFX) using X-ray free-electron lasers has produced high-resolution, room temperature, time-resolved protein structures. We report preliminary SFX of Sindbis virus, an enveloped icosahedral RNA virus with ~700 Å diameter. Microcrystals delivered in viscous agarose medium diffracted to ~40 Å resolution. Small-angle diffuse X-ray scattering overlaid Bragg peaks and analysis suggests this results from molecular transforms of individual particles. Viral proteins undergo structural changes during entry and infection, which could, in principle, be studied with SFX. This is a pertinent step toward determining room temperature structures from virus microcrystals that may enable time-resolved studies of enveloped viruses.

Evaluating the Use of Commercial West Nile Virus Antigens as Positive Controls in the Rapid Analyte Measurement Platform West Nile Virus Assay.

PubMed

Burkhalter, Kristen L; Savage, Harry M

2015-12-01

We evaluated the utility of 2 types of commercially available antigens as positive controls in the Rapid Analyte Measurement Platform (RAMP®) West Nile virus (WNV) assay. Purified recombinant WNV envelope antigens and whole killed virus antigens produced positive RAMP results and either type would be useful as a positive control. Killed virus antigens provide operational and economic advantages and we recommend their use over purified recombinant antigens. We also offer practical applications for RAMP positive controls and recommendations for preparing them.

First pathological report of a de novo CD5-positive diffuse large B-cell lymphoma patient presenting with Guillain-Barré syndrome-like neuropathy due to neurolymphomatosis.

PubMed

Kobayashi, Mikiko; Sakai, Yasuhiro; Kariya, Yuta; Sakai, Hitoshi; Hineno, Akiyo; Oyanagi, Kiyomitsu; Kanno, Hiroyuki

2018-05-02

Peripheral neuropathy occurs in approximately 5% of the patients with lymphoma. Two major causes of peripheral neuropathy associated with lymphoma are neurolymphomatosis and paraneoplastic neuropathy such as demyelinating neuropathy. The differential diagnosis between neurolymphomatosis and demyelinating neuropathy is difficult, because electrophysiological findings suggestive of demyelination are frequently observed even in patients with neurolymphomatosis. Here, we report a patient with de novo CD5-positive diffuse large B-cell lymphoma (DLBCL) who presented with Guillain-Barré syndrome (GBS)-like neuropathy. Demyelination due to paraneoplastic neuropathy was clinically suspected. However, autopsy demonstrated that the cause of the neuropathy was neurolymphomatosis. Clinical courses of neurolymphomatosis vary and neurolymphomatosis cases presenting with GBS-like neuropathy are reported. In addition, DLBCL is the most frequent histological type of malignant lymphoma that develops neurolymphomatosis. Furthermore, "CD5-positive" DLBCL may tend to develop neurolymphomatosis. If a patient with "CD5-positive" DLBCL develops peripheral neuropathy, neurolymphomatosis should be considered and imaging studies performed and, if possible, nerve tissue biopsy, regardless of clinical symptoms of the neuropathy. To our knowledge, this is the first report of a patient with de novo CD5-positive DLBCL with neurolymphomatosis who presented with GBS-like neuropathy. © 2018 Japanese Society of Neuropathology.

Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma

PubMed Central

Kiyasu, Junichi; Miyoshi, Hiroaki; Hirata, Akie; Arakawa, Fumiko; Ichikawa, Ayako; Niino, Daisuke; Sugita, Yasuo; Yufu, Yuji; Choi, Ilseung; Abe, Yasunobu; Uike, Naokuni; Nagafuji, Koji; Okamura, Takashi; Akashi, Koichi; Takayanagi, Ryoichi; Shiratsuchi, Motoaki

2015-01-01

Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The programmed cell death 1 (PD-1)/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1+ DLBCL. We performed PD-L1/PAX5 double immunostaining in 1253 DLBCL biopsy samples and established a new definition of PD-L1+ DLBCL. We also defined the criteria for microenvironmental PD-L1+ (mPD-L1+) DLBCL (ie, PD-L1– DLBCL in which PD-L1+ nonmalignant cells are abundant in the tumor microenvironment). Of the 273 patients whose clinical information was available, quantitative analysis of PD-1+ tumor-infiltrating lymphocytes (TILs) was performed. The prevalence rates of PD-L1+ and mPD-L1+ DLBCL were 11% and 15.3%, respectively. Both PD-L1+ and mPD-L1+ DLBCL were significantly associated with non–germinal center B-cell (GCB) type and Epstein-Barr virus positivity. The number of PD-1+ TILs was significantly higher in GCB-type tumors and lower in mPD-L1– and PD-L1+ DLBCL. Patients with PD-L1+ DLBCL had inferior overall survival (OS) compared with that in patients with PD-L1– DLBCL (P = .0009). In contrast, there was no significant difference in OS between mPD-L1+ and mPD-L1– DLBCL (P = .31). The expression of PD-L1 maintained prognostic value for OS in multivariate analysis (P = .0323). This is the first report describing the clinicopathological features and outcomes of PD-L1+ DLBCL. Immunotherapy targeting the PD-1/PD-L1 pathway should be considered in this distinct DLBCL subgroup. PMID:26239088

No Evidence for Xenotropic Murine Leukemia-Related Virus Infection in Sweden Using Internally Controlled Multiepitope Suspension Array Serology

PubMed Central

Blomberg, Fredrik; Sjösten, Anna; Sheikholvaezin, Ali; Bölin-Wiener, Agnes; Elfaitouri, Amal; Hessel, Sanna; Gottfries, Carl-Gerhard; Zachrisson, Olof; Öhrmalm, Christina; Jobs, Magnus; Pipkorn, Rüdiger

2012-01-01

Many syndromes have a large number of differential diagnoses, a situation which calls for multiplex diagnostic systems. Myalgic encephalomyelitis (ME), also named chronic fatigue syndrome (CFS), is a common disease of unknown etiology. A mouse retrovirus, xenotropic murine leukemia-related virus (XMRV), was found in ME/CFS patients and blood donors, but this was not corroborated. However, the paucity of serological investigations on XMRV in humans prompted us to develop a serological assay which cover many aspects of XMRV antigenicity. It is a novel suspension array method, using a multiplex IgG assay with nine recombinant proteins from the env and gag genes of XMRV and 38 peptides based on known epitopes of vertebrate gammaretroviruses. IgG antibodies were sought in 520 blood donors and 85 ME/CFS patients and in positive- and negative-control sera from animals. We found no differences in seroreactivity between blood donors and ME/CFS patients for any of the antigens. This did not support an association between ME/CFS and XMRV infection. The multiplex serological system had several advantages: (i) biotinylated protein G allowed us to run both human and animal sera, which is essential because of a lack of XMRV-positive humans; (ii) a novel quality control was a pan-peptide positive-control rabbit serum; and (iii) synthetic XMRV Gag peptides with degenerate positions covering most of the variation of murine leukemia-like viruses did not give higher background than nondegenerate analogs. The principle may be used for creation of variant tolerant peptide serologies. Thus, our system allows rational large-scale serological assays with built-in quality control. PMID:22787191

Novel divergent nidovirus in a python with pneumonia.

PubMed

Bodewes, Rogier; Lempp, Charlotte; Schürch, Anita C; Habierski, Andre; Hahn, Kerstin; Lamers, Mart; von Dörnberg, Katja; Wohlsein, Peter; Drexler, Jan Felix; Haagmans, Bart L; Smits, Saskia L; Baumgärtner, Wolfgang; Osterhaus, Albert D M E

2014-11-01

The order Nidovirales contains large, enveloped viruses with a non-segmented positive-stranded RNA genome. Nidoviruses have been detected in man and various animal species, but, to date, there have been no reports of nidovirus in reptiles. In the present study, we describe the detection, characterization, phylogenetic analyses and disease association of a novel divergent nidovirus in the lung of an Indian python (Python molurus) with necrotizing pneumonia. Characterization of the partial genome (>33 000 nt) of this virus revealed several genetic features that are distinct from other nidoviruses, including a very large polyprotein 1a, a putative ribosomal frameshift signal that was identical to the frameshift signal of astroviruses and retroviruses and an accessory ORF that showed some similarity with the haemagglutinin-neuraminidase of paramyxoviruses. Analysis of genome organization and phylogenetic analysis of polyprotein 1ab suggests that this virus belongs to the subfamily Torovirinae. Results of this study provide novel insights into the genetic diversity within the order Nidovirales. © 2014 The Authors.

[Pathomorphology of experimental infection caused by powassan virus isolated in the Primorskiĭ Territory].

PubMed

Isachkova, L M; Frolova, M P; Leonova, G N; Karmysheva, V Ia; Somov, G P

1978-01-01

Pathomorphology of the infection caused by Powassan virus strains isolated in the Primorsky Kray was studied in white mice. The central nervous system of the animals sacrificed in the time course of the infectious process was studied by light and luminescent microscopy. Severe diffuse inflammatory-degenerative changes were found in the brain and spinal cord. Immunofluorescence revealed cytoplasmic localization of the virus antigen in neurons, glial and connective tissue cells.

Multiscale Modeling of Virus Entry via Receptor-Mediated Endocytosis

NASA Astrophysics Data System (ADS)

Liu, Jin

2012-11-01

Virus infections are ubiquitous and remain major threats to human health worldwide. Viruses are intracellular parasites and must enter host cells to initiate infection. Receptor-mediated endocytosis is the most common entry pathway taken by viruses, the whole process is highly complex and dictated by various events, such as virus motions, membrane deformations, receptor diffusion and ligand-receptor reactions, occurring at multiple length and time scales. We develop a multiscale model for virus entry through receptor-mediated endocytosis. The binding of virus to cell surface is based on a mesoscale three dimensional stochastic adhesion model, the internalization (endocytosis) of virus and cellular membrane deformation is based on the discretization of Helfrich Hamiltonian in a curvilinear space using Monte Carlo method. The multiscale model is based on the combination of these two models. We will implement this model to study the herpes simplex virus entry into B78 cells and compare the model predictions with experimental measurements.

Optical tomography in the presence of void regions

PubMed

Dehghani; Arridge; Schweiger; Delpy

2000-09-01

There is a growing interest in the use of near-infrared spectroscopy for the noninvasive determination of the oxygenation level within biological tissue. Stemming from this application, there has been further research in the use of this technique for obtaining tomographic images of the neonatal head, with the view of determining the levels of oxygenated and deoxygenated blood within the brain. Owing to computational complexity, methods used for numerical modeling of photon transfer within tissue have usually been limited to the diffusion approximation of the Boltzmann transport equation. The diffusion approximation, however, is not valid in regions of low scatter, such as the cerebrospinal fluid. Methods have been proposed for dealing with nonscattering regions within diffusing materials through the use of a radiosity-diffusion model. Currently, this new model assumes prior knowledge of the void region location; therefore it is instructive to examine the errors introduced in applying a simple diffusion-based reconstruction scheme in cases in which there exists a nonscattering region. We present reconstructed images of objects that contain a nonscattering region within a diffusive material. Here the forward data is calculated with the radiosity-diffusion model, and the inverse problem is solved with either the radiosity-diffusion model or the diffusion-only model. The reconstructed images show that even in the presence of only a thin nonscattering layer, a diffusion-only reconstruction will fail. When a radiosity-diffusion model is used for image reconstruction, together with a priori information about the position of the nonscattering region, the quality of the reconstructed image is considerably improved. The accuracy of the reconstructed images depends largely on the position of the anomaly with respect to the nonscattering region as well as the thickness of the nonscattering region.

Evidence for an Ancestral Association of Human Coronavirus 229E with Bats

PubMed Central

Corman, Victor Max; Baldwin, Heather J.; Tateno, Adriana Fumie; Zerbinati, Rodrigo Melim; Annan, Augustina; Owusu, Michael; Nkrumah, Evans Ewald; Maganga, Gael Darren; Oppong, Samuel; Adu-Sarkodie, Yaw; Vallo, Peter; da Silva Filho, Luiz Vicente Ribeiro Ferreira; Leroy, Eric M.; Thiel, Volker; van der Hoek, Lia; Poon, Leo L. M.; Tschapka, Marco

2015-01-01

ABSTRACT We previously showed that close relatives of human coronavirus 229E (HCoV-229E) exist in African bats. The small sample and limited genomic characterizations have prevented further analyses so far. Here, we tested 2,087 fecal specimens from 11 bat species sampled in Ghana for HCoV-229E-related viruses by reverse transcription-PCR (RT-PCR). Only hipposiderid bats tested positive. To compare the genetic diversity of bat viruses and HCoV-229E, we tested historical isolates and diagnostic specimens sampled globally over 10 years. Bat viruses were 5- and 6-fold more diversified than HCoV-229E in the RNA-dependent RNA polymerase (RdRp) and spike genes. In phylogenetic analyses, HCoV-229E strains were monophyletic and not intermixed with animal viruses. Bat viruses formed three large clades in close and more distant sister relationships. A recently described 229E-related alpaca virus occupied an intermediate phylogenetic position between bat and human viruses. According to taxonomic criteria, human, alpaca, and bat viruses form a single CoV species showing evidence for multiple recombination events. HCoV-229E and the alpaca virus showed a major deletion in the spike S1 region compared to all bat viruses. Analyses of four full genomes from 229E-related bat CoVs revealed an eighth open reading frame (ORF8) located at the genomic 3′ end. ORF8 also existed in the 229E-related alpaca virus. Reanalysis of HCoV-229E sequences showed a conserved transcription regulatory sequence preceding remnants of this ORF, suggesting its loss after acquisition of a 229E-related CoV by humans. These data suggested an evolutionary origin of 229E-related CoVs in hipposiderid bats, hypothetically with camelids as intermediate hosts preceding the establishment of HCoV-229E. IMPORTANCE The ancestral origins of major human coronaviruses (HCoVs) likely involve bat hosts. Here, we provide conclusive genetic evidence for an evolutionary origin of the common cold virus HCoV-229E in hipposiderid bats by analyzing a large sample of African bats and characterizing several bat viruses on a full-genome level. Our evolutionary analyses show that animal and human viruses are genetically closely related, can exchange genetic material, and form a single viral species. We show that the putative host switches leading to the formation of HCoV-229E were accompanied by major genomic changes, including deletions in the viral spike glycoprotein gene and loss of an open reading frame. We reanalyze a previously described genetically related alpaca virus and discuss the role of camelids as potential intermediate hosts between bat and human viruses. The evolutionary history of HCoV-229E likely shares important characteristics with that of the recently emerged highly pathogenic Middle East respiratory syndrome (MERS) coronavirus. PMID:26378164

Vorinostat, Tacrolimus, and Methotrexate in Preventing GVHD After Stem Cell Transplant in Patients With Hematological Malignancies

ClinicalTrials.gov

2015-10-13

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Graft Versus Host Disease; Intraocular Lymphoma; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Chronic Lymphocytic Leukemia; Refractory Cytopenia With Multilineage Dysplasia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Central Nervous System Hodgkin Lymphoma; Secondary Central Nervous System Non-Hodgkin Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

Bluetongue virus RNA detection by real-time rt-PCR in post-vaccination samples from cattle.

PubMed

De Leeuw, I; Garigliany, M; Bertels, G; Willems, T; Desmecht, D; De Clercq, K

2015-04-01

Bluetongue virus serotype 8 (BTV-8) was responsible for a large outbreak among European ruminant populations in 2006-2009. In spring 2008, a massive vaccination campaign was undertaken, leading to the progressive disappearance of the virus. During surveillance programmes in Western Europe in 2010-2011, a low but significant number of animals were found weakly positive using BTV-specific real-time RT-PCR, raising questions about a possible low level of virus circulation. An interference of the BTV-8 inactivated vaccine on the result of the real-time RT-PCR was also hypothesized. Several studies specifically addressed the potential association between a recent vaccination and BTV-8 RNA detection in the blood of sheep. Results were contradictory and cattles were not investigated. To enlighten this point, a large study was performed to determine the risks of detection of bluetongue vaccine-associated RNA in the blood and spleen of cattle using real-time RT-PCR. Overall, the results presented clearly demonstrate that vaccine viral RNA can reach the blood circulation in sufficient amounts to be detected by real-time RT-PCR in cattle. This BTV-8 vaccine RNA carriage appears as short lasting. © 2013 Blackwell Verlag GmbH.

A large scale laboratory cage trial of Aedes densonucleosis virus (AeDNV).

PubMed

Wise de Valdez, Megan R; Suchman, Erica L; Carlson, Jonathan O; Black, William C

2010-05-01

Aedes aegypti (L.) (Diptera: Culicidae) the primary vector of dengue viruses (DENV1-4), oviposit in and around human dwellings, including sites difficult to locate, making control of this mosquito challenging. We explored the efficacy and sustainability of Aedes Densonucleosis Virus (AeDNV) as a biocontrol agent for Ae. aegypti in and among oviposition sites in large laboratory cages (> 92 m3) as a prelude to field trials. Select cages were seeded with AeDNV in a single oviposition site (OPS) with unseeded OPSs established at varied distances. Quantitative real-time polymerase chain reaction was used to track dispersal and accumulation of AeDNV among OPSs. All eggs were collected weekly from each cage and counted. We asked: (1) Is AeDNV dispersed over varying distances and can it accumulate and persist in novel OPSs? (2) Are egg densities reduced in AeDNV treated populations? AeDNV was dispersed to and sustained in novel OPSs. Virus accumulation in OPSs was positively correlated with egg densities and proximity to the initial infection source affected the timing of dispersal and maintenance of viral titers. AeDNV did not significantly reduce Ae. aegypti egg densities. The current study documents that adult female Ae. aegypti oviposition behavior leads to successful viral dispersal from treated to novel containers in large-scale cages; however, the AeDNV titers reached were not sufficient to reduce egg densities.

Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes

PubMed Central

2015-01-01

Background It is known that mRNA folding can affect and regulate various gene expression steps both in living organisms and in viruses. Previous studies have recognized functional RNA structures in the genome of the Dengue virus. However, these studies usually focused either on the viral untranslated regions or on very specific and limited regions at the beginning of the coding sequences, in a limited number of strains, and without considering evolutionary selection. Results Here we performed the first large scale comprehensive genomics analysis of selection for local mRNA folding strength in the Dengue virus coding sequences, based on a total of 1,670 genomes and 4 serotypes. Our analysis identified clusters of positions along the coding regions that may undergo a conserved evolutionary selection for strong or weak local folding maintained across different viral variants. Specifically, 53-66 clusters for strong folding and 49-73 clusters for weak folding (depending on serotype) aggregated of positions with a significant conservation of folding energy signals (related to partially overlapping local genomic regions) were recognized. In addition, up to 7% of these positions were found to be conserved in more than 90% of the viral genomes. Although some of the identified positions undergo frequent synonymous / non-synonymous substitutions, the selection for folding strength therein is preserved, and thus cannot be trivially explained based on sequence conservation alone. Conclusions The fact that many of the positions with significant folding related signals are conserved among different Dengue variants suggests that a better understanding of the mRNA structures in the corresponding regions may promote the development of prospective anti- Dengue vaccination strategies. The comparative genomics approach described here can be employed in the future for detecting functional regions in other pathogens with very high mutations rates. PMID:26449467

Placental Histopathology and Clinical Presentation of Severe Congenital Zika Syndrome in a Human Immunodeficiency Virus-Exposed Uninfected Infant.

PubMed

Rabelo, Kíssila; de Souza Campos Fernandes, Regina Célia; de Souza, Luiz José; Louvain de Souza, Thais; Dos Santos, Flávia Barreto; Guerra Nunes, Priscila Conrado; de Azeredo, Elzinandes Leal; Salomão, Natália Gedeão; Trindade, Gisela Freitas; Basílio-de-Oliveira, Carlos A; de Carvalho, Jorge José; Medina-Acosta, Enrique; Paes, Marciano Viana

2017-01-01

In the large Zika virus (ZIKV) epidemic that occurred in Brazil in 2015, the intrauterine fetal exposure to ZIKV was associated with a significant risk of developing microcephaly and neurological disorders in the infected infants. ZIKV-associated disease has since been reported in 24 countries in the Americas. At present, definitive evidence is lacking regarding the intrauterine co-exposure to ZIKV and other viral infections and whether the coinfection impacts the risk of acquiring either infection or disease severity. Here, we provide evidence of intrauterine exposure to both ZIKV and human immunodeficiency virus (HIV) infections, causing congenital Zika syndrome in an HIV-exposed uninfected infant. Clinical, imaging and laboratory examinations of the pregnant woman and the newborn were performed. Histopathology, ZIKV/HIV-specific immunoassays, and ultrastructural evaluation of the placenta were performed. The Zika-asymptomatic, HIV-positive pregnant woman underwent ultrasounds revealing fetal cerebral ventriculomegaly, microcephaly, and brain atrophy. Her baby girl was born small for gestational age and with the neurological sequelae of congenital Zika syndrome. The evaluation of the abnormally large term placenta revealed severe damage to the maternal decidua and chorionic villi, cells positive for ZIKV-specific antigens but not for HIV antigens, and intracellular membranous clusters of virus-like particles approximately 25 nm in diameter. The rapid progression and severity of the congenital Zika syndrome may be related to the uncontrolled HIV disease in the mother. The poor inflammatory response observed in the placenta may have reduced the inherent risk of mother-to-child transmission of HIV.

Placental Histopathology and Clinical Presentation of Severe Congenital Zika Syndrome in a Human Immunodeficiency Virus-Exposed Uninfected Infant

PubMed Central

Rabelo, Kíssila; de Souza Campos Fernandes, Regina Célia; de Souza, Luiz José; Louvain de Souza, Thais; dos Santos, Flávia Barreto; Guerra Nunes, Priscila Conrado; de Azeredo, Elzinandes Leal; Salomão, Natália Gedeão; Trindade, Gisela Freitas; Basílio-de-Oliveira, Carlos A.; de Carvalho, Jorge José; Medina-Acosta, Enrique; Paes, Marciano Viana

2017-01-01

In the large Zika virus (ZIKV) epidemic that occurred in Brazil in 2015, the intrauterine fetal exposure to ZIKV was associated with a significant risk of developing microcephaly and neurological disorders in the infected infants. ZIKV-associated disease has since been reported in 24 countries in the Americas. At present, definitive evidence is lacking regarding the intrauterine co-exposure to ZIKV and other viral infections and whether the coinfection impacts the risk of acquiring either infection or disease severity. Here, we provide evidence of intrauterine exposure to both ZIKV and human immunodeficiency virus (HIV) infections, causing congenital Zika syndrome in an HIV-exposed uninfected infant. Clinical, imaging and laboratory examinations of the pregnant woman and the newborn were performed. Histopathology, ZIKV/HIV-specific immunoassays, and ultrastructural evaluation of the placenta were performed. The Zika-asymptomatic, HIV-positive pregnant woman underwent ultrasounds revealing fetal cerebral ventriculomegaly, microcephaly, and brain atrophy. Her baby girl was born small for gestational age and with the neurological sequelae of congenital Zika syndrome. The evaluation of the abnormally large term placenta revealed severe damage to the maternal decidua and chorionic villi, cells positive for ZIKV-specific antigens but not for HIV antigens, and intracellular membranous clusters of virus-like particles approximately 25 nm in diameter. The rapid progression and severity of the congenital Zika syndrome may be related to the uncontrolled HIV disease in the mother. The poor inflammatory response observed in the placenta may have reduced the inherent risk of mother-to-child transmission of HIV. PMID:29270171

Changes in the intraisolate genetic structure of Beet necrotic yellow vein virus populations associated with plant resistance breakdown.

PubMed

Acosta-Leal, Rodolfo; Fawley, Marvin W; Rush, Charles M

2008-06-20

The causal agent of rhizomania disease, Beet necrotic yellow vein virus (BNYVV), typically produces asymptomatic root-limited infections in sugar beets (Beta vulgaris) carrying the Rz1-allele. Unfortunately, this dominant resistance has been recently overcome. Multiple cDNA clones of the viral pathogenic determinant p25, derived from populations infecting susceptible or resistant plants, were sequenced to identify host effects on the viral population structure. Populations isolated from compatible plant-virus interactions (susceptible plant-wild type virus and resistant plant-resistant breaking variants) were large and relatively homogeneous, whereas those from the incompatible interaction (resistant plant-avirulent type virus) were small and highly heterogeneous. All populations from susceptible plants had the same dominant haplotype, whereas those from resistant cultivars had a different haplotype surrounded by a spectrum of mutants. Selection and diversification analyses suggest an evolutionary trajectory of BNYVV with positive selection for changes required to overcome resistance, followed by elimination of hitchhiking mutations through purifying selection.

Cell adhesion and mechanics as drivers of tissue organization and differentiation: local cues for large scale organization.

PubMed

Wickström, Sara A; Niessen, Carien M

2018-06-01

Biological patterns emerge through specialization of genetically identical cells to take up distinct fates according to their position within the organism. How initial symmetry is broken to give rise to these patterns remains an intriguing open question. Several theories of patterning have been proposed, most prominently Turing's reaction-diffusion model of a slowly diffusing activator and a fast diffusing inhibitor generating periodic patterns. Although these reaction-diffusion systems can generate diverse patterns, it is becoming increasingly evident that cell shape and tension anisotropies, mediated via cell-cell and/or cell-matrix contacts, also facilitate symmetry breaking and subsequent self-organized tissue patterning. This review will highlight recent studies that implicate local changes in adhesion and/or tension as key drivers of cell rearrangements. We will also discuss recent studies on the role of cadherin and integrin adhesive receptors in mediating and responding to local tissue tension asymmetries to coordinate cell fate, position and behavior essential for tissue self-organization and maintenance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Polyomavirus-Negative Merkel Cell Carcinoma: A More Aggressive Subtype Based on Analysis of 282 Cases Using Multimodal Tumor Virus Detection.

PubMed

Moshiri, Ata S; Doumani, Ryan; Yelistratova, Lola; Blom, Astrid; Lachance, Kristina; Shinohara, Michi M; Delaney, Martha; Chang, Oliver; McArdle, Susan; Thomas, Hannah; Asgari, Maryam M; Huang, Meei-Li; Schwartz, Stephen M; Nghiem, Paul

2017-04-01

Previous studies have reached conflicting conclusions regarding the proportion of Merkel cell carcinomas (MCCs) that contain the Merkel cell polyomavirus (MCPyV) and the clinical significance of tumor viral status. To address these controversies, we detected MCPyV large T antigen using immunohistochemistry with two distinct antibodies and MCPyV DNA using quantitative PCR. Tumors were called MCPyV-positive if two or more of these three assays indicated presence of this virus. A total of 53 of 282 (19%) MCC tumors in this cohort were virus-negative using this multimodal system. Immunohistochemistry with the CM2B4 antibody had the best overall performance (sensitivity = 0.882, specificity = 0.943) compared with the multimodal classification. Multivariate analysis including age, sex, and immunosuppression showed that, relative to MCC patients with virus-positive tumors, virus-negative MCC patients had significantly increased risk of disease progression (hazard ratio = 1.77, 95% confidence interval = 1.20-2.62) and death from MCC (hazard ratio = 1.85, 95% confidence interval = 1.19-2.89). We confirm that approximately 20% of MCCs are not driven by MCPyV and that such virus-negative MCCs, which can be quite reliably identified by immunohistochemistry using the CM2B4 antibody alone, represent a more aggressive subtype that warrants closer clinical follow-up. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A miniaturized and integrated gel post platform for multiparameter PCR detection of herpes simplex viruses from raw genital swabs.

PubMed

Manage, Dammika P; Lauzon, Jana; Atrazhev, Alexey; Morrissey, Yuen C; Edwards, Ann L; Stickel, Alexander J; Crabtree, H John; Pabbaraju, Kanti; Zahariadis, George; Yanow, Stephanie K; Pilarski, Linda M

2012-05-07

Herpes simplex virus (HSV) is one of the most prevalent viruses, with acute and recurrent infections in humans. The current gold standard for the diagnosis of HSV is viral culture which takes 2-14 days and has low sensitivity. In contrast, DNA amplification by polymerase chain reaction (PCR) can be performed within 1-2 h. We here describe a multiparameter PCR assay to simultaneously detect HSV-1 and HSV-2 DNA templates, together with integrated positive and negative controls, with product detection by melting curve analysis (MCA), in an array of semi-solid polyacrylamide gel posts. Each gel post is 0.67 μL in volume, and polymerized with all the components required for PCR. Both PCR and MCA can currently be performed in one hour and 20 min. Unprocessed genital swabs collected in universal transport medium were directly added to the reagents before or after polymerization, diffusing from atop the gel posts. The gel post platform detects HSV templates in as little as 2.5 nL of raw sample. In this study, 45 genital swab specimens were tested blindly as a preliminary validation of this platform. The concordance of PCR on gel posts with conventional PCR was 91%. The primer sequestration method introduced here (wherein different primers are placed in different sets of posts) enables the simultaneous detection of multiple pathogens for the same sample, together with positive and negative controls, on a single chip. This platform accepts unprocessed samples and is readily adaptable to detection of multiple different pathogens or biomarkers for point-of-care diagnostics.

Positive-sense RNA viruses reveal the complexity and dynamics of the cellular and viral epitranscriptomes during infection.

PubMed

McIntyre, Will; Netzband, Rachel; Bonenfant, Gaston; Biegel, Jason M; Miller, Clare; Fuchs, Gabriele; Henderson, Eric; Arra, Manoj; Canki, Mario; Fabris, Daniele; Pager, Cara T

2018-06-20

More than 140 post-transcriptional modifications (PTMs) are known to decorate cellular RNAs, but their incidence, identity and significance in viral RNA are still largely unknown. We have developed an agnostic analytical approach to comprehensively survey PTMs on viral and cellular RNAs. Specifically, we used mass spectrometry to analyze PTMs on total RNA isolated from cells infected with Zika virus, Dengue virus, hepatitis C virus (HCV), poliovirus and human immunodeficiency virus type 1. All five RNA viruses significantly altered global PTM landscapes. Examination of PTM profiles of individual viral genomes isolated by affinity capture revealed a plethora of PTMs on viral RNAs, which far exceeds the handful of well-characterized modifications. Direct comparison of viral epitranscriptomes identified common and virus-specific PTMs. In particular, specific dimethylcytosine modifications were only present in total RNA from virus-infected cells, and in intracellular HCV RNA, and viral RNA from Zika and HCV virions. Moreover, dimethylcytosine abundance during viral infection was modulated by the cellular DEAD-box RNA helicase DDX6. By opening the Pandora's box on viral PTMs, this report presents numerous questions and hypotheses on PTM function and strongly supports PTMs as a new tier of regulation by which RNA viruses subvert the host and evade cellular surveillance systems.

Development of a Newcastle disease virus vector expressing a foreign gene through an internal ribosomal entry site provides direct proof for a sequential transcription mechanism.

PubMed

Zhang, Zhenyu; Zhao, Wei; Li, Deshan; Yang, Jinlong; Zsak, Laszlo; Yu, Qingzhong

2015-08-01

In the present study, we developed a novel approach for foreign gene expression by Newcastle disease virus (NDV) from a second ORF through an internal ribosomal entry site (IRES). Six NDV LaSota strain-based recombinant viruses vectoring the IRES and a red fluorescence protein (RFP) gene behind the nucleocapsid (NP), phosphoprotein (P), matrix (M), fusion (F), haemagglutinin-neuraminidase (HN) or large polymerase (L) gene ORF were generated using reverse genetics technology. The insertion of the second ORF slightly attenuated virus pathogenicity, but did not affect ability of the virus to grow. Quantitative measurements of RFP expression in virus-infected DF-1 cells revealed that the abundance of viral mRNAs and red fluorescence intensity were positively correlated with the gene order of NDV, 3'-NP-P-M-F-HN-L-5', proving the sequential transcription mechanism for NDV. The results herein suggest that the level of foreign gene expression could be regulated by selecting the second ORF insertion site to maximize the efficacy of vaccine and gene therapy.

Spatiotemporal Co-occurrence of Flanders and West Nile Viruses Within Culex Populations in Shelby County, Tennessee.

PubMed

Lucero, D E; Carlson, T C; Delisle, J; Poindexter, S; Jones, T F; Moncayo, A C

2016-05-01

West Nile virus (WNV) and Flanders virus (FLAV) can cocirculate in Culex mosquitoes in parts of North America. A large dataset of mosquito pools tested for WNV and FLAV was queried to understand the spatiotemporal relationship between these two viruses in Shelby County, TN. We found strong evidence of global clustering (i.e., spatial autocorrelation) and overlapping of local clustering (i.e., Hot Spots based on Getis Ord Gi*) of maximum likelihood estimates (MLE) of infection rates (IR) during 2008-2013. Temporally, FLAV emerges and peaks on average 10.2 wk prior to WNV based on IR. Higher levels of WNV IR were detected within 3,000 m of FLAV-positive pool buffers than outside these buffers. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Genetic diversity of bat orthohepadnaviruses in China and a proposed new nomenclature.

PubMed

Yang, Ling'en; Wu, Jianmin; Hu, Tingsong; Qin, Shaomin; Deng, Bo; Liu, Jinfeng; Zhang, Fuqiang; He, Biao; Tu, Changchun

2018-05-26

The orthohepadnaviruses, which include the major human pathogen hepatitis B virus, exist in a wide range of hosts. Since 2013, a large group of orthohepadnaviruses has been identified in bats worldwide and classified as 4 species within the genus Orthohepadnavirus. To further investigate orthohepadnaviruses in the Chinese bat population, 554 archived bat samples from 20 colonies covering 3 southern provinces were screened with results showing that 9 (1.6%) were positive. A systematic phylogenetic analysis has indicated the need for a new nomenclature for bat hepatitis B virus-like viruses: BtHBV, with the addition of 3 new species, one being divided into 6 genotypes. Viruses identified here shared 9.0-19.2% full genome divergence and classified into 3 different genotypes. This study illustrates the genetic diversity of orthohepadnaviruses in the Chinese bat population, and emphasizes need for further investigation of their public health significance. Copyright © 2018 Elsevier B.V. All rights reserved.

Cutaneous double-hit B-cell lymphoma: an aggressive form of B-cell lymphoma with a propensity for cutaneous dissemination.

PubMed

Magro, Cynthia M; Wang, Xuan; Subramaniyam, Shivakumar; Darras, Natasha; Mathew, Susan

2014-04-01

Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center cell lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 3 patients with an aggressive form of B-cell lymphoma secondarily involving the skin. Two of the patients were in the ninth decade of life, whereas 1 patient was 34 years of age. In the elderly patients, there was an antecedent and/or concurrent history of follicular lymphoma, whereas in the younger patient, the tumor was a de novo presentation of this aggressive form of lymphoma. The elderly patients succumbed to their disease within less than a year from the time of diagnosis, whereas 1 patient is alive but with persistent and progressive disease despite chemotherapeutic intervention. The infiltrates in all 3 cases were diffuse and composed of large malignant hematopoietic cells that exhibited a round nucleus with a finely dispersed chromatin. Phenotypically, the tumor cells were Bcl-2 and CD10 positive, whereas Bcl-6 and Mum-1 showed variable positivity. One case showed combined Mum-1 positivity along with an acute lymphoblastic lymphoma phenotype, including the absence of CD20 expression. In each case, there was a c-MYC and BCL2/IGH rearrangement diagnostic of double-hit lymphoma. In one case, there was an additional BCL6 rearrangement, defining what is in essence triple-hit lymphoma. In conclusion, double-hit lymphoma is an aggressive form of B-cell neoplasia resistant to standard chemotherapy regimens, which in many but not all cases represents tumor progression in the setting of a lower grade B-cell malignancy.

Detailed stress tensor measurements in a centrifugal compressor vaneless diffuser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinarbasi, A.; Johnson, M.W.

1996-04-01

Detailed flow measurements have been made in the vaneless diffuser of a large low-speed centrifugal compressor using hot-wire anemometry. The three time mean velocity components and full stress tensor distributions have been determined on eight measurement plans within the diffuser. High levels of Reynolds stress result in the rapid mixing out of the blade wake. Although high levels of turbulent kinetic energy are found in the passage wake, they are not associated with strong Reynolds stresses and hence the passage wake mixes out only slowly. Low-frequency meandering of the wake position is therefore likely to be responsible for the highmore » kinetic energy levels. The anisotropic nature of the turbulence suggests that Reynolds stress turbulence models are required for CFD modeling of diffuser flows.« less

Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2017-09-12

Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

S0349 Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Oblimersen in Treating Patients With Advanced Diffuse Large B-Cell Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2013-01-04

Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

The impact of HIV-related stigma on the lives of HIV-positive women: an integrated literature review.

PubMed

Ho, Szu-Szu; Holloway, Aisha

2016-01-01

To critically explore how Human Immunodeficiency Virus-related stigma impacts on the lives of Human Immunodeficiency Virus-positive women through an integrative review of the literature. Throughout history Human Immunodeficiency Virus infection has been associated with sex trade, injecting drug use and other deviant behaviours within society. These historical associations can lead to the generation of negative perceptions of Human Immunodeficiency Virus-positive women. As such, women who contract Human Immunodeficiency Virus infection can be susceptible to societal stigma. An integrative literature review. To identify the publications on the impact of Human Immunodeficiency Virus-related stigma among women, a search was performed using the following databases: CINAHL, Medline, PsycINFO, EMBASE, and Applied Social Sciences Index and Abstract covering the period from 2000-2014. The following key words were included in the search: 'women', 'Human Immunodeficiency Virus', and 'stigma'. Twenty-six articles were retrieved and reviewed. From the results, four key themes merged in relation to the impact of Human Immunodeficiency Virus-related stigma on Human Immunodeficiency Virus-positive women's lives: the individual, relationships, work and the community. Despite great advances in the management and treatment of those who are Human Immunodeficiency Virus positive, it appears the lives of many women living with Human Immunodeficiency Virus remain greatly affected by their Human Immunodeficiency Virus infection with gender-specific stigma and stereotypes. Having a holistic understanding of this impact offers the potential for those responsible for the funding and draws the attention of researchers and policy makers on promoting medical services specifically for Human Immunodeficiency Virus-positive women, minimising social stigmatisation towards this client group, and optimising their health outcomes. In an attempt to amplify Human Immunodeficiency Virus-positive women's ability to resist social injustice, obtain support and optimise their health outcomes, nurses should expand their roles and work with professionals from different sectors to ensure the provision of comprehensive care to women with Human Immunodeficiency Virus infection. © 2015 John Wiley & Sons Ltd.

Concentration of poliovirus from tap water using positively charged microporous filters.

PubMed Central

Sobsey, M D; Jones, B L

1979-01-01

Microporous filters that are more electropositive than the negatively charged filters currently used for virus concentrations from water by filter adsorption-elution methods were evaluated for poliovirus recovery from tap water. Zeta Plus filters composed of diatomaceous earth-cellulose-"charge-modified" resin mixtures and having a net positive charge of up to pH 5 to 6 efficiently adsorbed poliovirus from tap water at ambient pH levels 7.0 to 7.5 without added multivalent cation salts. The adsorbed virus were eluted with glycine-NaOH, pH 9.5 to 11.5. Electropositive asbestos-cellulose filters efficiently adsorbed poliovirus from tap water without added multivalent cation salts between pH 3.5 and 9.0, and the absorbed viruses could be eluted with 3% beef extract, pH 9, but not with pH 9.5 to 11.5 glycine-NaOH. Under water quality conditions in which poliovirus recoveries from large volumes of water were less than 5% with conventional negatively charged filters and standard methods, recoveries with Zeta Plus filters averaged 64 and 22.5% for one- and two-stage concentration procedures, respectively. Electropositive filters appear to offer distinct advantages over conventional negatively charged filters for concentrating enteric viruses from water, and their behavior tends to confirm the importance of electrostatic forces in virus recovery from water by microporous filter adsorption-elution methods. PMID:36844

Virus occurrence in private and public wells in a fractured dolostone aquifer in Canada

NASA Astrophysics Data System (ADS)

Allen, Amy S.; Borchardt, Mark A.; Kieke, Burney A.; Dunfield, Kari E.; Parker, Beth L.

2017-06-01

Groundwater samples from 22 wells completed in a regional fractured dolostone aquifer in the Guelph region of southern Ontario, Canada, were collected over an 8-month period and analyzed for viruses and Campylobacter jejuni. Only 8% of the 118 samples exhibited viruses at extremely low concentrations, but of the 22 wells sampled, 10 (45%) were positive for human enteric viruses (polyomavirus, adenovirus A, and GII norovirus) including 5 of the 8 public supply wells (62.5%) and 5 of the 11 private wells (45%). Each virus-positive well had only one virus occurrence with six sampling events during the 8-month sampling campaign and only one virus type was detected in each well. The probability of virus detection was positively associated with well open-interval length. Virus concentration (in the wells that were virus-positive) was negatively associated with well depth and open-interval length and positively associated with overburden thickness (i.e., the thickness of unconsolidated materials overlying bedrock facies) and the amount of precipitation 8-14 and 15-21 days prior to the sampling date. The ephemeral nature of the virus detections and the low detection rate on a per sample basis were consistent with previous studies. The percentage of virus-positive wells, however, was much higher than previous studies, but consistent with the fact that the hydrogeologic conditions of fractured bedrock aquifers create wide capture zones and short groundwater travel times to wells making them more vulnerable to contamination occurrence but at very low concentrations.

Effect of herd size on subclinical infection of swine in Vietnam with influenza A viruses.

PubMed

Takemae, Nobuhiro; Shobugawa, Yugo; Nguyen, Phuong Thanh; Nguyen, Tung; Nguyen, Tien Ngoc; To, Thanh Long; Thai, Phuong Duy; Nguyen, Tho Dang; Nguyen, Duy Thanh; Nguyen, Dung Kim; Do, Hoa Thi; Le, Thi Quynh Anh; Hua, Phan Truong; Van Vo, Hung; Nguyen, Diep Thi; Nguyen, Dang Hoang; Uchida, Yuko; Saito, Reiko; Saito, Takehiko

2016-10-10

Influenza A viruses of swine (IAV-S) cause acute and subclinical respiratory disease. To increase our understanding of the etiology of the subclinical form and thus help prevent the persistence of IAV-S in pig populations, we conducted active virologic surveillance in Vietnam, the second-largest pig-producing country in Asia, from February 2010 to December 2013. From a total of 7034 nasal swabs collected from clinically healthy pigs at 250 farms and 10 slaughterhouses, we isolated 172 IAV-S from swine at the weaning and early-fattening stages. The isolation rate of IAV-S was significantly higher among pigs aged 3 weeks to 4.5 months than in older and younger animals. IAV-S were isolated from 16 large, corporate farms and 6 family-operated farms from among the 250 farms evaluated. Multivariate logistic regression analysis revealed that "having more than 1,000 pigs" was the most influential risk factor for IAV-S positivity. Farms affected by reassortant IAV-S had significantly larger pig populations than did those where A(H1N1)pdm09 viruses were isolated, thus suggesting that large, corporate farms serve as sites of reassortment events. We demonstrate the asymptomatic circulation of IAV-S in the Vietnamese pig population. Raising a large number of pigs on a farm has the strongest impact on the incidence of subclinical IAV-S infection. Given that only some of the corporate farms surveyed were IAV-S positive, further active monitoring is necessary to identify additional risk factors important in subclinical infection of pigs with IAV-S in Vietnam.

Capture-ELISA for serum IgM antibody to respiratory syncytial virus.

PubMed Central

Cevenini, R.; Donati, M.; Bertini, S.; Moroni, A.; Sambri, V.

1986-01-01

A four-component solid-phase capture enzyme immunoassay was set up to test for serum IgM antibody to respiratory syncytial (RS) virus and was compared with immunofluorescence assay (IFA). A total of 128 young children with acute respiratory infections were studied. Thirty-six were shown to be RS virus-positive by the detection of RS virus in nasopharyngeal secretions and 92 were RS virus-negative. A serum specimen was collected after admission to the hospital (days 0-4) and a further specimen was obtained during days 10-14. Out of 36 RS virus-positive patients, 28 (77.7%) were found to be positive for IgM by both capture-ELISA and IFA. Out of 92 RS virus-negative patients 5 (5.4%) were IgM-positive. Four false-positive results were obtained by IFA due to the presence of rheumatoid factor. The capture-ELISA was shown to be a reliable technique in detecting specific IgM antibody to RS virus. PMID:3540115

Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies

ClinicalTrials.gov

2018-03-13

Burkitt Lymphoma; CD20-Positive Neoplastic Cells Present; Diffuse Large B-Cell Lymphoma; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Refractory Mature B-Cell Non-Hodgkin Lymphoma

Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients

ClinicalTrials.gov

2018-03-30

Acute Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Follicular Lymphoma; Graft Versus Host Disease; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Small Lymphocytic Lymphoma

Coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma with antecedent chronic lymphocytic leukemia: a case report and review of the literature.

PubMed

Abuelgasim, Khadega A; Rehan, Hinna; Alsubaie, Maha; Al Atwi, Nasser; Al Balwi, Mohammed; Alshieban, Saeed; Almughairi, Areej

2018-03-11

Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases. Here, we describe the first reported case of concurrent chronic myeloid leukemia and diffuse large B-cell lymphoma in a background of chronic lymphocytic leukemia. A 60-year-old Saudi man known to have diabetes, hypertension, and chronic active hepatitis B was diagnosed as having Rai stage II chronic lymphocytic leukemia, with trisomy 12 and rearrangement of the CCND1 gene in December 2012. He required no therapy until January 2016 when he developed significant anemia, thrombocytopenia, and constitutional symptoms. He received six cycles of fludarabine, cyclophosphamide, and rituximab, after which he achieved complete remission. One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly. Fluorescence in situ hybridization from bone marrow aspirate was positive for translocation (9;22) and reverse transcription polymerase chain reaction detected BCR-ABL fusion gene consistent with chronic myeloid leukemia. He had no morphologic or immunophenotypic evidence of chronic lymphocytic leukemia at the time. Imatinib, a first-line tyrosine kinase inhibitor, was started. Eight months later, a screening imaging revealed new liver lesions, which were confirmed to be diffuse large B-cell lymphoma. In chronic lymphocytic leukemia, progressive leukocytosis and splenomegaly caused by emerging chronic myeloid leukemia can be easily overlooked. It is unlikely that chronic myeloid leukemia arose as a result of clonal evolution secondary to fludarabine treatment given the very short interval after receiving fludarabine. It is also unlikely that imatinib contributed to the development of diffuse large B-cell lymphoma; rather, diffuse large B-cell lymphoma arose as a result of Richter's transformation. Fludarabine, trisomy 12, and CCND1 gene rearrangement might have increased the risk of Richter's transformation in this patient.

Influenza A virus strains that circulate in humans differ in the ability of their NS1 proteins to block the activation of IRF3 and interferon-β transcription.

PubMed

Kuo, Rei-Lin; Zhao, Chen; Malur, Meghana; Krug, Robert M

2010-12-20

We demonstrate that influenza A virus strains that circulate in humans differ markedly in the ability of their NS1 proteins to block the activation of IRF3 and interferon-β transcription. Strong activation occurs in cells infected with viruses expressing NS1 proteins of seasonal H3N2 and H2N2 viruses, whereas activation is blocked in cells infected with viruses expressing NS1 proteins of some, but not all seasonal H1N1 viruses. The NS1 proteins of the 2009 H1N1 and H5N1 viruses also block these activations. The difference in this NS1 function is mediated largely by the C-terminal region of the effector domain, which contains the only amino acid (K or E at position 196) that covaries with the functional difference. Further, we show that TRIM25 binds the NS1 protein whether or not IRF3 activation is blocked, demonstrating that binding of TRIM25 by the NS1 protein does not necessarily lead to the blocking of IRF3 activation. Copyright © 2010 Elsevier Inc. All rights reserved.

BCL2 and MYC are expressed at high levels in canine diffuse large B-cell lymphoma but are not predictive for outcome in dogs treated with CHOP chemotherapy.

PubMed

Curran, K M; Schaffer, P A; Frank, C B; Lana, S E; Hamil, L E; Burton, J H; Labadie, J; Ehrhart, E J; Avery, P R

2017-12-01

Diffuse large B-cell lymphoma (DLBCL) is the most common haematopoietic malignancy in dogs. Recently, MYC and BCL2 expression levels determined with immunohistochemistry (IHC) were found to be prognostic in people with DLBCL. We hypothesized that canine DLBCL can be similarly subdivided into prognostic subtypes based on expression of MYC and BCL2. Cases of canine DLBCL treated with CHOP chemotherapy were retrospectively collected and 43 dogs had available histologic tissue and complete clinical follow-up. Median values of percent immunoreactive versus immunonegative cells were used to determine positive or negative expression status. Completion of CHOP was significantly associated with a positive outcome. Compared with human patients, our canine DLBCL patients had high IHC expression of both MYC and BCL2, and relative expression levels of one or both markers were not associated with clinical outcome. © 2016 John Wiley & Sons Ltd.

Reactivation of Herpes Zoster Keratitis With Corneal Perforation After Zoster Vaccination.

PubMed

Jastrzebski, Andre; Brownstein, Seymour; Ziai, Setareh; Saleh, Solin; Lam, Kay; Jackson, W Bruce

2017-06-01

We present a case of reactivated herpes zoster keratouveitis of 6 years duration with corneal perforation requiring penetrating keratoplasty shortly after inoculation with herpes zoster vaccine (Zostavax, Merck, Quebec, Canada). Retrospective case report. A 67-year-old woman with a 5-year history of recurrent unilateral herpes zoster keratouveitis in her right eye presented with another recurrence 2 weeks after Zostavax vaccination. Three months later, she developed descemetocele and 2 months afterward, corneal perforation, which was managed by penetrating keratoplasty. Immunohistopathological examination disclosed positive staining for varicella zoster virus in most of the keratocytes adjacent to the descemetocele and perforation, most vividly in the deeper two-thirds of the stroma where the keratocytes were most dense, but not in corneal epithelium or endothelium. Electron microscopic examination showed universally severely degenerated corneal keratocytes in the corneal stroma adjacent to the perforation with variable numbers of herpes virus capsids present in half of these cells. Only a rare normal-appearing keratocyte was identified in the more peripheral corneal stroma. We present a case of reactivation of herpes keratouveitis shortly after vaccination with Zostavax in a patient with previous herpes zoster ophthalmicus. We demonstrate, for the first time, ultrastructural evidence consistent with inactive virus capsids in diffusely degenerated keratocytes in the extracted corneal tissue.

Seasonal pulses of Marburg virus circulation in juvenile Rousettus aegyptiacus bats coincide with periods of increased risk of human infection.

PubMed

Amman, Brian R; Carroll, Serena A; Reed, Zachary D; Sealy, Tara K; Balinandi, Stephen; Swanepoel, Robert; Kemp, Alan; Erickson, Bobbie Rae; Comer, James A; Campbell, Shelley; Cannon, Deborah L; Khristova, Marina L; Atimnedi, Patrick; Paddock, Christopher D; Crockett, Rebekah J Kent; Flietstra, Timothy D; Warfield, Kelly L; Unfer, Robert; Katongole-Mbidde, Edward; Downing, Robert; Tappero, Jordan W; Zaki, Sherif R; Rollin, Pierre E; Ksiazek, Thomas G; Nichol, Stuart T; Towner, Jonathan S

2012-01-01

Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ~2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (~six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a basis for developing Marburg hemorrhagic fever risk reduction strategies.

Seasonal Pulses of Marburg Virus Circulation in Juvenile Rousettus aegyptiacus Bats Coincide with Periods of Increased Risk of Human Infection

PubMed Central

Amman, Brian R.; Carroll, Serena A.; Reed, Zachary D.; Sealy, Tara K.; Balinandi, Stephen; Swanepoel, Robert; Kemp, Alan; Erickson, Bobbie Rae; Comer, James A.; Campbell, Shelley; Cannon, Deborah L.; Khristova, Marina L.; Atimnedi, Patrick; Paddock, Christopher D.; Kent Crockett, Rebekah J.; Flietstra, Timothy D.; Warfield, Kelly L.; Unfer, Robert; Katongole-Mbidde, Edward; Downing, Robert; Tappero, Jordan W.; Zaki, Sherif R.; Rollin, Pierre E.; Ksiazek, Thomas G.; Nichol, Stuart T.; Towner, Jonathan S.

2012-01-01

Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ∼2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (∼six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a basis for developing Marburg hemorrhagic fever risk reduction strategies. PMID:23055920

Histopathological evaluation of the diversity of cells susceptible to H5N1 virulent avian influenza virus.

PubMed

Ogiwara, Haru; Yasui, Fumihiko; Munekata, Keisuke; Takagi-Kamiya, Asako; Munakata, Tsubasa; Nomura, Namiko; Shibasaki, Futoshi; Kuwahara, Kazuhiko; Sakaguchi, Nobuo; Sakoda, Yoshihiro; Kida, Hiroshi; Kohara, Michinori

2014-01-01

Patients infected with highly pathogenic avian influenza A H5N1 viruses (H5N1 HPAIV) show diffuse alveolar damage. However, the temporal progression of tissue damage and repair after viral infection remains poorly defined. Therefore, we assessed the sequential histopathological characteristics of mouse lung after intranasal infection with H5N1 HPAIV or H1N1 2009 pandemic influenza virus (H1N1 pdm). We determined the amount and localization of virus in the lung through IHC staining and in situ hybridization. IHC used antibodies raised against the virus protein and antibodies specific for macrophages, type II pneumocytes, or proliferating cell nuclear antigen. In situ hybridization used RNA probes against both viral RNA and mRNA encoding the nucleoprotein and the hemagglutinin protein. H5N1 HPAIV infection and replication were observed in multiple lung cell types and might result in rapid progression of lung injury. Both type II pneumocytes and macrophages proliferated after H5N1 HPAIV infection. However, the abundant macrophages failed to block the viral attack, and proliferation of type II pneumocytes failed to restore the damaged alveoli. In contrast, mice infected with H1N1 pdm exhibited modest proliferation of type II pneumocytes and macrophages and slight alveolar damage. These results suggest that the virulence of H5N1 HPAIV results from the wide range of cell tropism of the virus, excessive virus replication, and rapid development of diffuse alveolar damage. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Histopathological Evaluation of the Diversity of Cells Susceptible to H5N1 Virulent Avian Influenza Virus

PubMed Central

Ogiwara, Haru; Yasui, Fumihiko; Munekata, Keisuke; Takagi-Kamiya, Asako; Munakata, Tsubasa; Nomura, Namiko; Shibasaki, Futoshi; Kuwahara, Kazuhiko; Sakaguchi, Nobuo; Sakoda, Yoshihiro; Kida, Hiroshi; Kohara, Michinori

2015-01-01

Patients infected with highly pathogenic avian influenza A H5N1 viruses (H5N1 HPAIV) show diffuse alveolar damage. However, the temporal progression of tissue damage and repair after viral infection remains poorly defined. Therefore, we assessed the sequential histopathological characteristics of mouse lung after intranasal infection with H5N1 HPAIV or H1N1 2009 pandemic influenza virus (H1N1 pdm). We determined the amount and localization of virus in the lung through IHC staining and in situ hybridization. IHC used antibodies raised against the virus protein and antibodies specific for macrophages, type II pneumocytes, or proliferating cell nuclear antigen. In situ hybridization used RNA probes against both viral RNA and mRNA encoding the nucleoprotein and the hemagglutinin protein. H5N1 HPAIV infection and replication were observed in multiple lung cell types and might result in rapid progression of lung injury. Both type II pneumocytes and macrophages proliferated after H5N1 HPAIV infection. However, the abundant macrophages failed to block the viral attack, and proliferation of type II pneumocytes failed to restore the damaged alveoli. In contrast, mice infected with H1N1 pdm exhibited modest proliferation of type II pneumocytes and macrophages and slight alveolar damage. These results suggest that the virulence of H5N1 HPAIV results from the wide range of cell tropism of the virus, excessive virus replication, and rapid development of diffuse alveolar damage. PMID:24200852

High-Performance Ink-Synthesized Cu-Gate Thin-Film Transistor with Diffusion Barrier Formation

NASA Astrophysics Data System (ADS)

Woo, Whang Je; Nam, Taewook; Oh, Il-Kwon; Maeng, Wanjoo; Kim, Hyungjun

2018-02-01

The improved electrical properties of Cu-gate thin-film transistors (TFTs) using an ink-synthesizing process were studied; this technology enables a low-cost and large area process for the display industry. We investigated the film properties and the effects of the ink-synthesized Cu layer in detail with respect to device characteristics. The mobility and reliability of the devices were significantly improved by applying a diffusion barrier at the interface between the Cu gate and the gate insulator. By using a TaN diffusion barrier layer, considerably improved and stabilized ink-Cu gated TFTs could be realized, comparable to sputtered-Cu gated TFTs under positive bias temperature stress measurements.

High-Performance Ink-Synthesized Cu-Gate Thin-Film Transistor with Diffusion Barrier Formation

NASA Astrophysics Data System (ADS)

Woo, Whang Je; Nam, Taewook; Oh, Il-Kwon; Maeng, Wanjoo; Kim, Hyungjun

2018-05-01

The improved electrical properties of Cu-gate thin-film transistors (TFTs) using an ink-synthesizing process were studied; this technology enables a low-cost and large area process for the display industry. We investigated the film properties and the effects of the ink-synthesized Cu layer in detail with respect to device characteristics. The mobility and reliability of the devices were significantly improved by applying a diffusion barrier at the interface between the Cu gate and the gate insulator. By using a TaN diffusion barrier layer, considerably improved and stabilized ink-Cu gated TFTs could be realized, comparable to sputtered-Cu gated TFTs under positive bias temperature stress measurements.

Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

ClinicalTrials.gov

2018-06-25

Diffuse Large B-Cell Lymphoma Activated B-Cell Type; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; High Grade B-Cell Lymphoma, Not Otherwise Specified; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Ocular abnormalities in congenital Zika syndrome: a case report, and review of the literature.

PubMed

Guevara, Jade Gieseke; Agarwal-Sinha, Swati

2018-06-09

As the number of children with Zika virus-related complications grows, the long-term developmental trajectory and its effects on families are unknown. We present the first known case of congenital Zika syndrome seen at our institution with significant fundus findings. A 3-day-old Hispanic baby girl presented with severe microcephaly of 24 cm and temperature instability at birth. Her mother had traveled to Honduras early in pregnancy and testing of amniotic fluid was positive for Zika virus via polymerase chain reaction. A dilated fundus examination was significant for bilateral severe colobomatous chorioretinal atrophy of the macula and pigmentary changes. Neonatal magnetic resonance imaging revealed diffuse lissencephaly with decreased brain volume, atrophic corpus callosum and brainstem, periventricular calcifications, and ventriculomegaly of the lateral ventricles. Our patient, who presented with the first known case of congenital Zika syndrome in Northern Florida, demonstrated profound bilateral colobomatous chorioretinal atrophy of the macula. The ophthalmologic findings along with severe microcephaly emphasize the neurotropism of the Zika virus, and ultimately are indicative of poor developmental and visual prognosis for affected infants. With the increased prevalence of Zika virus, ophthalmologists should be aware of the associated findings and the importance of an eye-screening examination with a dilated fundus examination within 1 month of life of infants in which congenital Zika syndrome is suspected. A multidisciplinary care approach is essential for the care of affected infants and their families.

Association of interferon lambda-1 with herpes simplex viruses-1 and -2, Epstein-Barr virus, and human cytomegalovirus in chronic periodontitis.

PubMed

Muzammil; Jayanthi, D; Faizuddin, Mohamed; Noor Ahamadi, H M

2017-05-01

Periodontal tissues facilitate the homing of herpes viruses that elicit the immune-inflammatory response releasing the interferons (IFN). IFN lambda-1 (λ1) can suppress the replication of viruses, and induces the antiviral mechanism. The aim of the present study was to evaluate the association between IFN-λ1 and periodontal herpes viruses in the immunoregulation of chronic periodontal disease. The cross-sectional study design included 30 chronic periodontitis patients with a mean age of 42.30 ± 8.63 years. Gingival crevicular fluid collected was assessed for IFN-λ1 using enzyme-linked immunosorbent assay and four herpes viruses were detected using multiplex polymerase chain reaction technique. IFN-λ1 levels were compared between virus-positive and -negative patients for individual and total viruses. Fifty per cent (n = 15) of patients were positive for the four herpes viruses together; 50% (n = 15), 30% (n = 9), 26.7% (n = 8), and 40% (n = 12) were positive for herpes simplex virus (HSV)-1, Epstein-Barr virus, HSV-2, and human cytomegalovirus, respectively. The mean concentrations of IFN-λ1 in virus-positive patients (14.38 ± 13.95) were lower than those of virus-negative patients (228.26 ± 215.35). INF-λ1 levels in individual virus groups were also lower in virus-positive patients compared to virus-negative patients, with P < 0.001. These results suggest that IFN-λ1 could have antiviral and therapeutic value against the viruses in the pathogenesis of chronic periodontitis. © 2015 Wiley Publishing Asia Pty Ltd.

9 CFR 113.47 - Detection of extraneous viruses by the fluorescent antibody technique.

Code of Federal Regulations, 2010 CFR

2010-01-01

...; (ii) Reovirus; and (iii) Rabies virus. (2) Bovine, caprine, and ovine cells shall, in addition, be... have rabies virus on premises either for research or production purposes are exempt from having to produce positive rabies virus control monolayers. Fixed positive rabies virus control monolayers will be...

Bioaerosol Sampling in Modern Agriculture: A Novel Approach for Emerging Pathogen Surveillance?

PubMed Central

Anderson, Benjamin D.; Ma, Mengmeng; Xia, Yao; Wang, Tao; Shu, Bo; Lednicky, John A.; Ma, Mai-Juan; Lu, Jiahai; Gray, Gregory C.

2016-01-01

Background. Modern agricultural practices create environmental conditions conducive to the emergence of novel pathogens. Current surveillance efforts to assess the burden of emerging pathogens in animal production facilities in China are sparse. In Guangdong Province pig farms, we compared bioaerosol surveillance for influenza A virus to surveillance in oral pig secretions and environmental swab specimens. Methods. During the 2014 summer and fall/winter seasons, we used 3 sampling techniques to study 5 swine farms weekly for influenza A virus. Samples were molecularly tested for influenza A virus, and positive specimens were further characterized with culture. Risk factors for influenza A virus positivity for each sample type were assessed. Results. Seventy-one of 354 samples (20.1%) were positive for influenza A virus RNA by real-time reverse-transcription polymerase chain reaction analysis. Influenza A virus positivity in bioaerosol samples was a statistically significant predictor for influenza A virus positivity in pig oral secretion and environmental swab samples. Temperature of <20°C was a significant predictor of influenza A virus positivity in bioaerosol samples. Discussions. Climatic factors and routine animal husbandry practices may increase the risk of human exposure to aerosolized influenza A viruses in swine farms. Data suggest that bioaerosol sampling in pig barns may be a noninvasive and efficient means to conduct surveillance for novel influenza viruses. PMID:27190187

Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment

PubMed Central

Carbone, Antonino; Gloghini, Annunziata

2013-01-01

The relationships between lymphomas and their microenvironment appear to follow 3 major patterns: (1) an independent pattern; (2) a dependent pattern on deregulated interactions; and (3) a dependent pattern on regulated coexistence. Typical examples of the third pattern are hepatitis C virus (HCV)-associated marginal zone lymphomas (MZLs) and mucosa-associated lymphoid tissue lymphomas. In these lymphomas, a regulated coexistence of the malignant cells and the microenvironmental factors usually occurs. At least initially, however, tumor development and cell growth largely depend on external signals from the microenvironment, such as viral antigens, cytokines, and cell-cell interactions. The association between HCV infection and B-cell lymphomas is not completely defined, although this association has been demonstrated by epidemiological studies. MZL and diffuse large B-cell lymphoma are the histotypes most frequently associated with HCV infection. Many mechanisms have been proposed for explaining HCV-induced lymphomagenesis; antigenic stimulation by HCV seems to be fundamental in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B-cell lymphomas. Recently, antiviral treatment has been proved to be effective in the treatment of HCV-associated indolent lymphomas. Importantly, clinically responses were linked to the eradication of the HCV-RNA, providing a strong argument in favor of a causative link between HCV and lymphoproliferation. PMID:24307781

EDs on heightened alert for MERS-CoV as first cases reach the US.

PubMed

2014-07-01

The first cases of Middle East Respiratory Syndrome coronavirus (MERS-CoV) have turned up in the United States. First, in late April, a patient tested positive for the virus at a hospital in Munster, IN, and then shortly thereafter, a second patient tested positive at a hospital in Orlando, FL. While both patients have since recovered from the virus and been released, the cases have raised awareness of the infectious threat of MERS-CoV, and they have put EDs and other frontline providers on heightened alert for patients with severe respiratory symptoms and other risk factors. While MERS-CoV is not yet as contagious as seasonal influenza or the severe acute respiratory syndrome (SARS) that started in China and then swept around the globe in 2003, it is more deadly. The World Health Organization reports that roughly one-quarter of 514 people who have tested positive for the virus have died. Experts note that health care workers make up a large percentage of the documented cases of MERS-CoV, and they point out that most human-to-human transmissions of the virus occur in the hospital setting. Public health officials urge emergency personnel to pay strict attention to infection control practices, and to query patients who present with fever and respiratory distress about recent travel to the Arabian Peninsula and/or close contact with a person who has a confirmed or probable case of MERS-CoV.

Herpes viruses and human papilloma virus in nasal polyposis and controls.

PubMed

Ioannidis, Dimitrios; Lachanas, Vasileios A; Florou, Zoe; Bizakis, John G; Petinaki, Efthymia; Skoulakis, Charalampos E

2015-01-01

Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p=0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%, p=0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

The PA-Gene-Mediated Lethal Dissemination and Excessive Innate Immune Response Contribute to the High Virulence of H5N1 Avian Influenza Virus in Mice

PubMed Central

Hu, Jiao; Hu, Zenglei; Song, Qingqing; Gu, Min; Liu, Xiaowen; Wang, Xiaoquan; Hu, Shunlin; Chen, Chaoyang; Liu, Huimou; Liu, Wenbo; Chen, Sujuan; Peng, Daxin

2013-01-01

Highly pathogenic H5N1 influenza A virus remains a substantial threat to public health. To understand the molecular basis and host mechanism for the high virulence of H5N1 viruses in mammals, we compared two H5N1 isolates which have similar genetic backgrounds but greatly differ in their virulence in mice. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly pathogenic, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is nonpathogenic. We first showed that CK10 elicited a more potent innate immune response than did GS10 in mouse lungs by increasing the number and expression levels of activated genes. We then generated a series of reassortants between the two viruses and evaluated their virulence in mice. Inclusion of the CK10 PA gene in the GS10 background resulted in a dramatic increase in virulence. Conversely, expression of the GS10 PA gene in the CK10 background significantly attenuated the virulence. These results demonstrated that the PA gene mainly determines the pathogenicity discrepancy between CK10 and GS10 in mice. We further determined that arginine (R) at position 353 of the PA gene contributes to the high virulence of CK10 in mice. The reciprocal substitution at position 353 in PA or the exchange of the entire PA gene largely caused the transfer of viral phenotypes, including virus replication, polymerase activity, and manipulation of the innate response, between CK10 and GS10. We therefore defined a novel molecular marker associated with the high virulence of H5N1 influenza viruses, providing further insights into the pathogenesis of H5N1 viruses in mammals. PMID:23255810

Phytoalexin induction in rubiaceae.

PubMed

Braga, M R; Claudia, M; Young, M; Dietrich, S M; Gottlieb, O R

1991-06-01

Phytoalexin responses were measured by modified drop-diffusate and facilitated diffusion techniques after fungal inoculation of leaves of 32 Rubiaceae species from Brazilian forest and savanna. Such responses presented a trend similar to that previously observed for a broad sample of dicotyledonous plants and are more frequently positive for the more primitive (or slower growing) trees than for the advanced (or faster growing) herbs. Fifteen of these species analyzed during a one-year period showed that positive phytoalexin responses are stronger for the rainy (and hotter) than for the dry (and cooler) season. Species that contain relatively large quantities of phenolics gave invariably negative responses. Positive responses are not necessarily associated with the appearance of new substances within leaf tissue and are thus caused by inhibitins rather than by phytoalexins. These results are discussed recognizing that the tested plants are subject to the multifarious influences of their natural environment and of a possible conjugate-caused compartmentation of plant metabolites.

Ebola Virus RNA in Semen from an HIV-Positive Survivor of Ebola.

PubMed

Purpura, Lawrence J; Rogers, Emerson; Baller, April; White, Stephen; Soka, Moses; Choi, Mary J; Mahmoud, Nuha; Wasunna, Christine; Massaquoi, Moses; Kollie, Jomah; Dweh, Straker; Bemah, Philip; Ladele, Victor; Kpaka, Jonathan; Jawara, Mary; Mugisha, Margaret; Subah, Onyekachi; Faikai, Mylene; Bailey, Jeff A; Rollin, Pierre; Marston, Barbara; Nyenswah, Tolbert; Gasasira, Alex; Knust, Barbara; Nichol, Stuart; Williams, Desmond

2017-04-01

Ebola virus is known to persist in semen of male survivors of Ebola virus disease (EVD). However, maximum duration of, or risk factors for, virus persistence are unknown. We report an EVD survivor with preexisting HIV infection, whose semen was positive for Ebola virus RNA 565 days after recovery from EVD.

Ultrasensitive Detection of RNA and DNA Viruses Simultaneously Using Duplex UNDP-PCR Assay

PubMed Central

Wang, Zengguo; Zhang, Xiujuan; Zhao, Xiaomin; Du, Qian; Chang, Lingling; Tong, Dewen

2015-01-01

Mixed infection of multiple viruses is common in modern intensive pig rearing. However, there are no methods available to detect DNA and RNA viruses in the same reaction system in preclinical level. In this study, we aimed to develop a duplex ultrasensitive nanoparticle DNA probe-based PCR assay (duplex UNDP-PCR) that was able to simultaneously detect DNA and RNA viruses in the same reaction system. PCV2 and TGEV are selected as representatives of the two different types of viruses. PCV2 DNA and TGEV RNA were simultaneously released from the serum sample by boiling with lysis buffer, then magnetic beads and gold nanoparticles coated with single and/or duplex specific probes for TGEV and PCV2 were added to form a sandwich-like complex with nucleic acids released from viruses. After magnetic separation, DNA barcodes specific for PCV2 and TGEV were eluted using DTT and characterized by specific PCR assay for specific DNA barcodes subsequently. The duplex UNDP-PCR showed similar sensitivity as that of single UNDP-PCR and was able to detect 20 copies each of PCV2 and TGEV in the serum, showing approximately 250-fold more sensitivity than conventional duplex PCR/RT-PCR assays. No cross-reaction was observed with other viruses. The positive detection rate of single MMPs- and duplex MMPs-based duplex UNDP-PCR was identical, with 29.6% for PCV2, 9.3% for TGEV and 3.7% for PCV2 and TGEV mixed infection. This duplex UNDP-PCR assay could detect TGEV (RNA virus) and PCV2 (DNA virus) from large-scale serum samples simultaneously without the need for DNA/RNA extraction, purification and reverse transcription of RNA, and showed a significantly increased positive detection rate for PCV2 (29%) and TGEV (11.7%) preclinical infection than conventional duplex PCR/RT-PCR. Therefore, the established duplex UNDP-PCR is a rapid and economical detection method, exhibiting high sensitivity, specificity and reproducibility. PMID:26544710

Ultrasensitive Detection of RNA and DNA Viruses Simultaneously Using Duplex UNDP-PCR Assay.

PubMed

Huang, Yong; Xing, Na; Wang, Zengguo; Zhang, Xiujuan; Zhao, Xiaomin; Du, Qian; Chang, Lingling; Tong, Dewen

2015-01-01

Mixed infection of multiple viruses is common in modern intensive pig rearing. However, there are no methods available to detect DNA and RNA viruses in the same reaction system in preclinical level. In this study, we aimed to develop a duplex ultrasensitive nanoparticle DNA probe-based PCR assay (duplex UNDP-PCR) that was able to simultaneously detect DNA and RNA viruses in the same reaction system. PCV2 and TGEV are selected as representatives of the two different types of viruses. PCV2 DNA and TGEV RNA were simultaneously released from the serum sample by boiling with lysis buffer, then magnetic beads and gold nanoparticles coated with single and/or duplex specific probes for TGEV and PCV2 were added to form a sandwich-like complex with nucleic acids released from viruses. After magnetic separation, DNA barcodes specific for PCV2 and TGEV were eluted using DTT and characterized by specific PCR assay for specific DNA barcodes subsequently. The duplex UNDP-PCR showed similar sensitivity as that of single UNDP-PCR and was able to detect 20 copies each of PCV2 and TGEV in the serum, showing approximately 250-fold more sensitivity than conventional duplex PCR/RT-PCR assays. No cross-reaction was observed with other viruses. The positive detection rate of single MMPs- and duplex MMPs-based duplex UNDP-PCR was identical, with 29.6% for PCV2, 9.3% for TGEV and 3.7% for PCV2 and TGEV mixed infection. This duplex UNDP-PCR assay could detect TGEV (RNA virus) and PCV2 (DNA virus) from large-scale serum samples simultaneously without the need for DNA/RNA extraction, purification and reverse transcription of RNA, and showed a significantly increased positive detection rate for PCV2 (29%) and TGEV (11.7%) preclinical infection than conventional duplex PCR/RT-PCR. Therefore, the established duplex UNDP-PCR is a rapid and economical detection method, exhibiting high sensitivity, specificity and reproducibility.

Evolution and Antiviral Specificities of Interferon-Induced Mx Proteins of Bats against Ebola, Influenza, and Other RNA Viruses

PubMed Central

Fuchs, Jonas; Hölzer, Martin; Schilling, Mirjam; Patzina, Corinna; Schoen, Andreas; Zimmer, Gert; Marz, Manja; Müller, Marcel A.

2017-01-01

ABSTRACT Bats serve as a reservoir for various, often zoonotic viruses, including significant human pathogens such as Ebola and influenza viruses. However, for unknown reasons, viral infections rarely cause clinical symptoms in bats. A tight control of viral replication by the host innate immune defense might contribute to this phenomenon. Transcriptomic studies revealed the presence of the interferon-induced antiviral myxovirus resistance (Mx) proteins in bats, but detailed functional aspects have not been assessed. To provide evidence that bat Mx proteins might act as key factors to control viral replication we cloned Mx1 cDNAs from three bat families, Pteropodidae, Phyllostomidae, and Vespertilionidae. Phylogenetically these bat Mx1 genes cluster closely with their human ortholog MxA. Using transfected cell cultures, minireplicon systems, virus-like particles, and virus infections, we determined the antiviral potential of the bat Mx1 proteins. Bat Mx1 significantly reduced the polymerase activity of viruses circulating in bats, including Ebola and influenza A-like viruses. The related Thogoto virus, however, which is not known to infect bats, was not inhibited by bat Mx1. Further, we provide evidence for positive selection in bat Mx1 genes that might explain species-specific antiviral activities of these proteins. Together, our data suggest a role for Mx1 in controlling these viruses in their bat hosts. IMPORTANCE Bats are a natural reservoir for various viruses that rarely cause clinical symptoms in bats but are dangerous zoonotic pathogens, like Ebola or rabies virus. It has been hypothesized that the interferon system might play a key role in controlling viral replication in bats. We speculate that the interferon-induced Mx proteins might be key antiviral factors of bats and have coevolved with bat-borne viruses. This study evaluated for the first time a large set of bat Mx1 proteins spanning three major bat families for their antiviral potential, including activity against Ebola virus and bat influenza A-like virus, and we describe here their phylogenetic relationship, revealing patterns of positive selection that suggest a coevolution with viral pathogens. By understanding the molecular mechanisms of the innate resistance of bats against viral diseases, we might gain important insights into how to prevent and fight human zoonotic infections caused by bat-borne viruses. PMID:28490593

Evolution and Antiviral Specificities of Interferon-Induced Mx Proteins of Bats against Ebola, Influenza, and Other RNA Viruses.

PubMed

Fuchs, Jonas; Hölzer, Martin; Schilling, Mirjam; Patzina, Corinna; Schoen, Andreas; Hoenen, Thomas; Zimmer, Gert; Marz, Manja; Weber, Friedemann; Müller, Marcel A; Kochs, Georg

2017-08-01

Bats serve as a reservoir for various, often zoonotic viruses, including significant human pathogens such as Ebola and influenza viruses. However, for unknown reasons, viral infections rarely cause clinical symptoms in bats. A tight control of viral replication by the host innate immune defense might contribute to this phenomenon. Transcriptomic studies revealed the presence of the interferon-induced antiviral myxovirus resistance (Mx) proteins in bats, but detailed functional aspects have not been assessed. To provide evidence that bat Mx proteins might act as key factors to control viral replication we cloned Mx1 cDNAs from three bat families, Pteropodidae, Phyllostomidae, and Vespertilionidae. Phylogenetically these bat Mx1 genes cluster closely with their human ortholog MxA. Using transfected cell cultures, minireplicon systems, virus-like particles, and virus infections, we determined the antiviral potential of the bat Mx1 proteins. Bat Mx1 significantly reduced the polymerase activity of viruses circulating in bats, including Ebola and influenza A-like viruses. The related Thogoto virus, however, which is not known to infect bats, was not inhibited by bat Mx1. Further, we provide evidence for positive selection in bat Mx1 genes that might explain species-specific antiviral activities of these proteins. Together, our data suggest a role for Mx1 in controlling these viruses in their bat hosts. IMPORTANCE Bats are a natural reservoir for various viruses that rarely cause clinical symptoms in bats but are dangerous zoonotic pathogens, like Ebola or rabies virus. It has been hypothesized that the interferon system might play a key role in controlling viral replication in bats. We speculate that the interferon-induced Mx proteins might be key antiviral factors of bats and have coevolved with bat-borne viruses. This study evaluated for the first time a large set of bat Mx1 proteins spanning three major bat families for their antiviral potential, including activity against Ebola virus and bat influenza A-like virus, and we describe here their phylogenetic relationship, revealing patterns of positive selection that suggest a coevolution with viral pathogens. By understanding the molecular mechanisms of the innate resistance of bats against viral diseases, we might gain important insights into how to prevent and fight human zoonotic infections caused by bat-borne viruses. Copyright © 2017 American Society for Microbiology.

MMS Encounters with Reconnection Diffusion Regions in the Earth's Magnetotail

NASA Astrophysics Data System (ADS)

Torbert, R. B.; Burch, J. L.; Argall, M. R.; Farrugia, C. J.; Alm, L.; Dors, I.; Payne, D.; Rogers, A. J.; Strangeway, R. J.; Phan, T.; Ergun, R.; Goodrich, K.; Lindqvist, P. A.; Khotyaintsev, Y. V.; Giles, B. L.; Rager, A. C.; Gershman, D. J.; Kletzing, C.

2017-12-01

The Magnetospheric Multiscale (MMS) fleet of four spacecraft traversed the Earth's magnetotail in May through August of 2017 with an apogee of 25 Re, and encountered diffusion regions characteristic of symmetric reconnection. This presentation will describe in-situ measurements of large electric fields, strong electron cross-tail and Hall currents, and electron velocity distributions (frequently crescent-shaped) that are commonly observed in these regions. Positive electromagnetic energy conversion is also typical. The characteristics of symmetric reconnection observations will be contrasted with those of asymmetric reconnection that MMS observed previously at the dayside magnetopause.

Central Rotations of Milky Way Globular Clusters

NASA Astrophysics Data System (ADS)

Fabricius, Maximilian H.; Noyola, Eva; Rukdee, Surangkhana; Saglia, Roberto P.; Bender, Ralf; Hopp, Ulrich; Thomas, Jens; Opitsch, Michael; Williams, Michael J.

2014-06-01

Most Milky Way globular clusters (GCs) exhibit measurable flattening, even if on a very low level. Both cluster rotation and tidal fields are thought to cause this flattening. Nevertheless, rotation has only been confirmed in a handful of GCs, based mostly on individual radial velocities at large radii. We are conducting a survey of the central kinematics of Galactic GCs using the new Integral Field Unit instrument VIRUS-W. We detect rotation in all 11 GCs that we have observed so far, rendering it likely that a large majority of the Milky Way GCs rotate. We use published catalogs of GCs to derive central ellipticities and position angles. We show that in all cases where the central ellipticity permits an accurate measurement of the position angle, those angles are in excellent agreement with the kinematic position angles that we derive from the VIRUS-W velocity fields. We find an unexpected tight correlation between central rotation and outer ellipticity, indicating that rotation drives flattening for the objects in our sample. We also find a tight correlation between central rotation and published values for the central velocity dispersion, most likely due to rotation impacting the old dispersion measurements. This Letter includes data taken at The McDonald Observatory of The University of Texas at Austin.

Speckle field as a multiple particle trap

NASA Astrophysics Data System (ADS)

Shvedov, V. G.; Rode, A. V.; Izdebskaya, Ya. V.; Desyatnikov, A. S.; Krolikowski, W.; Kivshar, Yu. S.

2010-04-01

We demonstrate that a speckle pattern in the spatially coherent laser field transmitted by a diffuser forms a multitude of three-dimensional bottle-shaped micro-traps. These multiple traps serve as a means for an effective trapping of large number of air-born absorbing particles. Confinement of up to a few thousand particles in air with a single beam has been achieved. The ability to capture light-absorbing particles suspended in gases by optical means opens up rich and diverse practical opportunities, including development of photonic shielding/fencing for environmental protection in nanotechnology industry and new methods of touch-free air transport of particles and small containers, which may hold dangerous substances, or viruses and living cells.

Re-evaluating TTF-1 immunohistochemistry in diffuse gliomas: Expression is clone-dependent and associated with tumor location.

PubMed

Pratt, Drew; Afsar, Nina; Allgauer, Michael; Fetsch, Patricia; Palisoc, Maryknoll; Pittaluga, Stefania; Quezado, Martha

TTF-1 is widely used as a marker in routine surgical pathology in the work-up of malignancy. Aberrant expression of TTF-1 in extrapulmonary and extrathyroidal malignancies is a frequently reported phenomenon. In addition to the recently characterized pituicyte-derived tumors of the sella, immunoreactivity has been reported in diffuse gliomas with the SPT24 clone. Here, we sought to evaluate TTF-1 expression with three commercially available clones in a large series of gliomas. Expression was compared across the newly defined diagnostic entities in the 2016 WHO Classification of CNS Tumors. Using tissue microarrays (TMA), 212 diffuse gliomas (WHO grades II - IV) were systematically evaluated with TTF-1 immunohistochemistry using three clones: SPT24, 8G7G3/1, and SP141, and results correlated with clinicopathologic features. 14 high-grade diffuse gliomas demonstrated nuclear staining with the SP141 and SPT24 clones. Two tumors showed weak positivity with the 8G7G3/1 clone. All tumors were high grade by histology (WHO grades III and IV). 86% (12/14) of TTF-1-positive gliomas involved the frontal lobes at diagnosis. No relationship with IDH R132H, ATRX, p53, H3K27M, or EGFR immunohistochemistry was identified. TTF-1 expression in gliomas was not independently prognostic of overall survival. TTF-1 expression in diffuse gliomas is a rare but potentially misleading occurrence. In our cohort, staining occurred with both the SPT24 and SP141 clones at equal intensity and frequency. Clustering of TTF-1-positive tumors in the frontal lobe(s) suggests lineage-specific expression. Due to clone-specific expression in diffuse gliomas, caution must be exercised in the work-up of intracranial tumors with TTF-1.
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A Diffusive-Particle Theory of Free Recall

PubMed Central

Fumarola, Francesco

2017-01-01

Diffusive models of free recall have been recently introduced in the memory literature, but their potential remains largely unexplored. In this paper, a diffusive model of short-term verbal memory is considered, in which the psychological state of the subject is encoded as the instantaneous position of a particle diffusing over a semantic graph. The model is particularly suitable for studying the dependence of free-recall observables on the semantic properties of the words to be recalled. Besides predicting some well-known experimental features (forward asymmetry, semantic clustering, word-length effect), a novel prediction is obtained on the relationship between the contiguity effect and the syllabic length of words; shorter words, by way of their wider semantic range, are predicted to be characterized by stronger forward contiguity. A fresh analysis of archival free-recall data allows to confirm this prediction. PMID:29085521

Development and evaluation of a recombinant-glycoprotein-based latex agglutination test for rabies virus antibody assessment.

PubMed

Jemima, Ebenezer Angel; Manoharan, Seeralan; Kumanan, Kathaperumal

2014-08-01

The measurement of neutralizing antibodies induced by the glycoprotein of rabies virus is indispensable for assessing the level of neutralizing antibodies in animals or humans. A rapid fluorescent focus inhibition test (RFFIT) has been approved by WHO and is the most widely used method to measure the virus-neutralizing antibody content in serum, but a rapid test system would be of great value to screen large numbers of serum samples. To develop and evaluate a latex agglutination test (LAT) for measuring rabies virus antibodies, a recombinant glycoprotein was expressed in an insect cell system and purified, and the protein was coated onto latex beads at concentrations of 0.1, 0.25, 0.5, 0.75, and 1 mg/ml to find out the optimal concentration for coating latex beads. It was found that 0.5 mg/ml of recombinant protein was optimal for coating latex beads, and this concentration was used to sensitize the latex beads for screening of dog serum samples. Grading of LAT results was done with standard reference serum with known antibody titers. A total of 228 serum samples were tested, out of which 145 samples were positive by both RFFIT and LAT, and the specificity was found to be 100 %. In RFFIT, 151 samples were positive, the sensitivity was found to be 96.03 %, and the accuracy/concordance was found to be 97.39 %. A rapid field test-a latex agglutination test (LAT)-was developed and evaluated for rabies virus antibody assessment using recombinant glycoprotein of rabies virus expressed in an insect cell system.

GOLDEN2-LIKE transcription factors coordinate the tolerance to Cucumber mosaic virus in Arabidopsis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Xue-Ying; Li, Peng-Xu; Zou, Li-Juan

Arabidopsis thaliana GOLDEN2-LIKE (GLKs) transcription factors play important roles in regulation of photosynthesis-associated nuclear genes, as well as participate in chloroplast development. However, the involvement of GLKs in plants resistance to virus remains largely unknown. Here, the relationship between GLKs and Cucumber mosaic virus (CMV) stress response was investigated. Our results showed that the Arabidopsis glk1glk2 double-mutant was more susceptible to CMV infection and suffered more serious damages (such as higher oxidative damages, more compromised in PSII photochemistry and more reactive oxygen species accumulation) when compared with the wild-type plants. Interestingly, there was little difference between single mutant (glk1 ormore » glk2) and wild-type plants in response to CMV infection, suggesting GLK1 and GLK2 might function redundant in virus resistance in Arabidopsis. Furthermore, the induction of antioxidant system and defense-associated genes expression in the double mutant were inhibited when compared with single mutant or wild-type plants after CMV infection. Further evidences showed that salicylic acid (SA) and jasmonic acid (JA) might be involved in GLKs-mediated virus resistance, as SA or JA level and synthesis-related genes transcription were impaired in glk1glk2 mutant. Taken together, our results indicated that GLKs played a positively role in virus resistance in Arabidopsis. - Highlights: • GLKs play a positive role in CMV resistance in Arabidopsis. • Defective of GLKs suffered more ROS accumulation. • Arabidopsis lacking GLKs have damaged photosynthesis. • Arabidopsis lacking GLKs show low SA and JA accumulation.« less

Isolation and Characterization of Metallosphaera turreted icosahedral virus (MTIV), a founding member of a new family of archaeal viruses.

PubMed

Wagner, Cassia; Reddy, Vijay; Asturias, Francisco; Khoshouei, Maryam; Johnson, John E; Manrique, Pilar; Munson-McGee, Jacob; Baumeister, Wolfgang; Lawrence, C Martin; Young, Mark J

2017-08-02

Our understanding of archaeal virus diversity and structure is just beginning to emerge. Here we describe a new archaeal virus, tentatively named Metallosphaera turreted icosahedral virus (MTIV), that was isolated from an acidic hot spring in Yellowstone National Park, USA. Two strains of the virus were identified and found to replicate in an archaeal host species closely related to Metallosphaera yellowstonensis Each strain encodes for a 9.8-9.9 kb, linear dsDNA genome with large inverted terminal repeats. Each genome encodes for 21 ORFs. Between the strains the ORFs display high homology, but they are quite distinct from other known viral genes. The 70-nm diameter virion is built upon on a T=28 icosahedral lattice. Both single particle cryo-electron microscopy and cryo-tomography reconstructions reveal an unusual structure that has 42 turret-like projections: 12 from each of the 5-fold axes and 30 hexameric units positioned on icosahedral 2-fold axes. Both the virion structural properties and genome content support MTIV as the founding member of a new family of archaeal viruses. Importance: Many archaeal viruses are quite different than viruses infecting bacteria and eukaryotes. Initial characterization of MTIV reveals a virus distinct from other known bacterial, eukaryotic, and archaeal viruses; this finding suggests that viruses infecting Archaea are still an understudied group of viruses. As the first known virus infecting the Metallosphaera , MTIV provides a new system for exploring archaeal virology by examining host-virus interactions and the unique features of MTIV structure-function relationships. These studies will likely expand our understanding of virus ecology and evolution. Copyright © 2017 American Society for Microbiology.

Ilarviruses of Prunus spp.: a continued concern for fruit trees.

PubMed

Pallas, V; Aparicio, F; Herranz, M C; Amari, K; Sanchez-Pina, M A; Myrta, A; Sanchez-Navarro, J A

2012-12-01

Prunus spp. are affected by a large number of viruses, causing significant economic losses through either direct or indirect damage, which results in reduced yield and fruit quality. Among these viruses, members of the genus Ilarvirus (isometric labile ringspot viruses) occupy a significant position due to their distribution worldwide. Although symptoms caused by these types of viruses were reported early in the last century, their molecular characterization was not achieved until the 1990s, much later than for other agronomically relevant viruses. This was mainly due to the characteristic liability of virus particles in tissue extracts. In addition, ilarviruses, together with Alfalfa mosaic virus, are unique among plant viruses in that they require a few molecules of the coat protein in the inoculum in order to be infectious, a phenomenon known as genome activation. Another factor that has made the study of this group of viruses difficult is that infectious clones have been obtained only for the type member of the genus, Tobacco streak virus. Four ilarviruses, Prunus necrotic ringspot virus, Prune dwarf virus, Apple mosaic virus, and American plum line pattern virus, are pathogens of the main cultivated fruit trees. As stated in the 9th Report of the International Committee on Taxonomy of Viruses, virions of this genus are "unpromising subjects for the raising of good antisera." With the advent of molecular approaches for their detection and characterization, it has been possible to get a more precise view of their prevalence and genome organization. This review updates our knowledge on the incidence, genome organization and expression, genetic diversity, modes of transmission, and diagnosis, as well as control of this peculiar group of viruses affecting fruit trees.

Multistage adsorption of diffusing macromolecules and viruses

NASA Astrophysics Data System (ADS)

Chou, Tom; D'Orsogna, Maria R.

2007-09-01

We derive the equations that describe adsorption of diffusing particles onto a surface followed by additional surface kinetic steps before being transported across the interface. Multistage surface kinetics occurs during membrane protein insertion, cell signaling, and the infection of cells by virus particles. For example, viral entry into healthy cells is possible only after a series of receptor and coreceptor binding events occurs at the cellular surface. We couple the diffusion of particles in the bulk phase with the multistage surface kinetics and derive an effective, integrodifferential boundary condition that contains a memory kernel embodying the delay induced by the surface reactions. This boundary condition takes the form of a singular perturbation problem in the limit where particle-surface interactions are short ranged. Moreover, depending on the surface kinetics, the delay kernel induces a nonmonotonic, transient replenishment of the bulk particle concentration near the interface. The approach generalizes that of Ward and Tordai [J. Chem. Phys. 14, 453 (1946)] and Diamant and Andelman [Colloids Surf. A 183-185, 259 (2001)] to include surface kinetics, giving rise to qualitatively new behaviors. Our analysis also suggests a simple scheme by which stochastic surface reactions may be coupled to deterministic bulk diffusion.

Simian virus 40-related antigens in three human meningiomas with defined chromosome loss.

PubMed Central

Weiss, A F; Portmann, R; Fischer, H; Simon, J; Zang, K D

1975-01-01

Two out of seven meningiomas tested in early cell cultures by indirect immunofluorescence staining showed simian virus 40 (SV40)-related tumor (T) antigen. In one tumor 90% of the cells were positive. An additional SV40-related antigen (U) was found in 10% of cells of a third tumor. These findings indicate that the meningioma cells showing a positive reaction are transformed by a papova virus that has at least partly the same antigenic properties as SV40 virus. SV40-related viral capsid (V) antigen was absent in all the meningiomas tested. No virus infectious for African green monkey kidney (AGMK) cells could be isolated. The tumors positive for T and U antigens showed the chromosome aberration typical for human meningiomas, i.e., the loss of one chromosome, G-22. The T-antigen-positive tumors showed further hypodiploidization. Experiments to rescue virus from the T-antigen-positive tumors showed further hypodiploidization. Experiments to rescue virus from the T-antigen-positive meningioma cells were performed: fusion of cells pretreated with 8-azaguanine with cells premissive for SV40 led to a low percentage (0.01-0.05%) of V-antigen-positive nuclei in heterokaryon cultures. On the basis of these results, the possibility of a correlation between the meningioma, a relatively common intracranial tumor in man, and an SV40-related papova virus must be considered. It remains to be shown whether this virus is a causative agent for human meningiomas. Images PMID:164660

Isolation of human monoclonal antibodies to the envelope e2 protein of hepatitis C virus and their characterization.

PubMed

Shimizu, Yohko K; Hijikata, Minako; Oshima, Masamichi; Shimizu, Kazufumi; Alter, Harvey J; Purcell, Robert H; Yoshikura, Hiroshi; Hotta, Hak

2013-01-01

We isolated and characterized two human monoclonal antibodies to the envelope E2 protein of hepatitis C virus (HCV). Lymphoblastoid cell lines stably producing antibodies were obtained by immortalizing peripheral blood mononuclear cells of a patient with chronic hepatitis C using Epstein-Barr virus. Screening for antibody-positive clones was carried out by immunofluorescence with Huh7 cells expressing the E2 protein of HCV strain H (genotype 1a) isolated from the same patient. Isotype of resulting antibodies, #37 and #55, was IgG1/kappa and IgG1/lambda, respectively. Epitope mapping revealed that #37 and #55 recognize conformational epitopes spanning amino acids 429 to 652 and 508 to 607, respectively. By immunofluorescence using virus-infected Huh7.5 cells as targets both antibodies were reactive with all of the nine different HCV genotypes/subtypes tested. The antibodies showed a different pattern of immuno-staining; while #37 gave granular reactions mostly located in the periphery of the nucleus, #55 gave diffuse staining throughout the cytoplasm. Both antibodies were shown by immuno-gold electron microscopy to bind to intact viral particles. In a neutralization assay (focus-forming unit reduction using chimeric infectious HCV containing structural proteins derived from genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, 6a, and 7a), #55 inhibited the infection of all HCV genotypes tested but genotype 7a to a lesser extent. #37 did not neutralize any of these viruses. As a broadly cross-neutralizing human antibody, #55 may be useful for passive immunotherapy of HCV infection.

Atezolizumab, Gemcitabine, Oxaliplatin, and Rituximab in Treating Patients With Relapsed or Refractory Transformed Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2018-06-06

Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Transformed Indolent Non-Hodgkin Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Systematic CpT (ApG) depletion and CpG excess are unique genomic signatures of large DNA viruses infecting invertebrates.

PubMed

Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal

2014-01-01

Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts.

Bent paths of a positive streamer and a cathode-directed spark leader in diffuse discharges preionized by runaway electrons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Cheng; Shao, Tao, E-mail: st@mail.iee.ac.cn; Wang, Ruixue

2015-03-15

Diffuse discharges preionized by runaway electrons can produce large-area homogeneous discharges at elevated pressures, which is an intriguing phenomenon in the physics of pulsed discharges. In this paper, runaway-electron-preionized diffuse discharge (REP DD) was obtained in a wide pressure range (0.05–0.25 MPa), and under certain conditions a positive streamer and a cathode-directed spark leader could be observed to propagate at some angles to the applied (background) electric field lines. For a 16-mm gap at an air pressure of 0.08–0.1 MPa, the percentage of pulses in which such propagation is observed is about 5%–50% of their total number, and in the other pulsesmore » such bent paths could not be observed because there is even no streamer or cathode-directed spark leader in diffuse discharges. In our opinion, such propagation of the positive streamer and the cathode-directed spark leader at some angle to the background electric field lines owes to different increase rates of the electron density in different regions of the discharge volume under REP DD conditions. Therefore, during the formation of a REP DD, the increase of the electron density is inhomogeneous and nonsimultaneous, resulting in an electron density gradient at the ionization wave front.« less

Ebola Virus RNA in Semen from an HIV-Positive Survivor of Ebola

PubMed Central

Rogers, Emerson; Baller, April; White, Stephen; Soka, Moses; Choi, Mary J.; Mahmoud, Nuha; Wasunna, Christine; Massaquoi, Moses; Kollie, Jomah; Dweh, Straker; Bemah, Philip; Ladele, Victor; Kpaka, Jonathan; Jawara, Mary; Mugisha, Margaret; Subah, Onyekachi; Faikai, Mylene; Bailey, Jeff A.; Rollin, Pierre; Marston, Barbara; Nyenswah, Tolbert; Gasasira, Alex; Knust, Barbara; Nichol, Stuart; Williams, Desmond

2017-01-01

Ebola virus is known to persist in semen of male survivors of Ebola virus disease (EVD). However, maximum duration of, or risk factors for, virus persistence are unknown. We report an EVD survivor with preexisting HIV infection, whose semen was positive for Ebola virus RNA 565 days after recovery from EVD. PMID:28287374

Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma

ClinicalTrials.gov

2017-10-24

Composite Lymphoma; Grade 3b Follicular Lymphoma; Stage I Diffuse Large B-Cell Lymphoma; Stage I Follicular Lymphoma; Stage II Diffuse Large B-Cell Lymphoma; Stage II Follicular Lymphoma; Stage III Diffuse Large B-Cell Lymphoma; Stage III Follicular Lymphoma; Stage IV Diffuse Large B-Cell Lymphoma; Stage IV Follicular Lymphoma

Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C.

PubMed

Cacoub, P; Renou, C; Rosenthal, E; Cohen, P; Loury, I; Loustaud-Ratti, V; Yamamoto, A M; Camproux, A C; Hausfater, P; Musset, L; Veyssier, P; Raguin, G; Piette, J C

2000-01-01

From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV infection in a large cohort of HCV patients, to identify associations between clinical and biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral coinfections with HIV and/or hepatitis B virus, connective tissue diseases, and a wide panel of autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including arthralgia (60/321, 19%), skin manifestations (55/321, 17%), xerostomia (40/321, 12%), xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main biologic abnormalities were mixed cryoglobulins (110/196, 56%), thrombocytopenia (50/291, 17%), and the presence of the following autoantibodies: antinuclear (123/302, 41%), rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%), antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1 autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with cryoglobulin positivity: systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2), rheumatoid factor positivity (p = 0.01, OR = 2.8), and sicca syndrome (p = 0.03, OR = 0.27). A definite connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed cryoglobulinemia and systemic vasculitis, HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18), thrombocytopenia (p = 0.01, OR = 3.56), and arthralgia or myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented more severe histologic lesions (p = 0.0004). Extrahepatic clinical manifestations in HCV patients involve primarily the skin and joints. The most frequent immunologic abnormalities include mixed cryoglobulins, rheumatoid factor, antinuclear, anticardiolipin, and antithyroglobulin antibodies. Cryoglobulin positivity is associated with systemic vasculitis and rheumatoid factor and HIV positivity. HIV coinfection is associated with arthralgia or myalgia, anticardiolipin antibodies, and thrombocytopenia.

Seborrheic Keratosis-like Lesions of the Cervix and Vagina: Report of a New Entity Possibly Related to Low-risk Human Papillomavirus Infection.

PubMed

Talia, Karen L; McCluggage, W Glenn

2017-04-01

We report a series of 7 unusual and morphologically distinct cervical or upper vaginal lesions in women aged 41 to 70 years. The lesions involved the cervix in 3 cases, the upper vagina in 2, the cervix and vagina in 1, and in 1 case the site of origin could not be determined. The lesions had a consistent morphologic appearance with a surface "plaque-like" or "stuck-on" configuration apparent in those cases where surrounding normal tissues were present. Broad coalescing solid sheets and interconnecting trabeculae of cytologically bland cells with a rather "basaloid" appearance emanated from the surface and there were scattered squamous eddies. Other features included peripheral palisading and a stroma containing hyalinized basement membrane-like material. Immunohistochemically, the lesions were diffusely positive with p63, CK5/6, and 34βE12 and focally positive with CK7, but largely negative with CK20, EMA, CEA, and BerEP4. p16 was negative or exhibited nonblock-type immunoreactivity and GATA3 was negative or weakly positive. Molecular testing detected human papillomavirus type 42 in 3 of 7 cases, with no virus detected in the remaining 4 cases. Rarely, similar cases have been reported previously as inverted transitional papilloma of the cervix or vagina, but based on the morphology and immunophenotype we do not feel these represent transitional lesions. We suggest the term seborrheic keratosis-like lesions to designate this new and rare entity, which may be associated with low-risk human papillomavirus infection. Limited follow-up in a small number of cases suggests that these lesions follow a benign clinical course.

Evaluation of Altona Diagnostics RealStar Zika Virus Reverse Transcription-PCR Test Kit for Zika Virus PCR Testing

PubMed Central

Lombos, Ernesto; Tang, Elaine; Perusini, Stephen; Eshaghi, Alireza; Nagra, Sandeep; Frantz, Christine; Olsha, Romy; Kristjanson, Erik; Dimitrova, Kristina; Safronetz, David; Drebot, Mike

2017-01-01

ABSTRACT With the emerging Zika virus (ZIKV) epidemic, accessible real-time reverse transcription-PCR (rRT-PCR) assays are needed to streamline testing. The commercial Altona Diagnostics RealStar ZIKV rRT-PCR test kit (Altona PCR) has been approved for emergency use authorization by the U.S. FDA. Our aim was to verify the Altona PCR by comparing it to the CDC-designed dual-target ZIKV rRT-PCR reference assay (reference PCR) and describe the demographics of patients tested for ZIKV by rRT-PCR in Ontario, Canada. A large set of clinical specimens was tested for ZIKV by the Altona PCR and the reference PCR. Positive or equivocal specimens underwent PCR and Sanger sequencing targeting the ZIKV NS5 gene. A total of 671 serum specimens were tested by the reference PCR: 58 (8.6%) were positive, 193 (28.8%) were equivocal, and 420 (62.6%) were negative. Ninety percent of the reference PCR-positive patients were tested in the first 5 days after symptom onset. The Altona PCR was performed on 284/671 specimens tested by the reference PCR. The Altona PCR was positive for 53/58 (91%) reference PCR-positive specimens and 16/193 (8%) reference PCR-equivocal specimens; the ZIKV NS5 PCR was positive for all 68 Altona PCR-positive specimens and negative for all 181 Altona PCR-negative specimens that underwent the NS5 PCR. The Altona PCR has very good sensitivity (91%) and specificity (97%) compared to the reference PCR. The Altona PCR can be used for ZIKV diagnostic testing and has less extensive verification requirements than a laboratory-developed test. PMID:28298448

A report on the outbreak of Zika virus on Easter Island, South Pacific, 2014.

PubMed

Tognarelli, J; Ulloa, S; Villagra, E; Lagos, J; Aguayo, C; Fasce, R; Parra, B; Mora, J; Becerra, N; Lagos, N; Vera, L; Olivares, B; Vilches, M; Fernández, J

2016-03-01

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus circulating in Asia and Africa. In 2013, a large outbreak was reported on the archipelago of French Polynesia. In this study, we report the detection and molecular characterization of Zika virus for the first time in Chile from an outbreak among the inhabitants of Easter Island. A total of 89 samples from patients suspected of having ZIKV infection were collected between the period from January to May, 2014. Molecular diagnosis of the virus was performed by RT-PCR followed by the sequencing of the region containing the NS5 gene. A comparison of the viral nucleic acid sequence with those of other strains of ZIKA virus was performed using the MEGA software. Fifty-one samples were found positive for ZIKV by RT-PCR analysis. Further analysis of the NS5 gene revealed that the ZIKV strains identified in Easter Island were most closely related to those found in French Polynesia (99.8 to 99.9% nt and 100% aa sequence identity). These results strongly suggest that the transmission pathway leading to the introduction of Zika virus on Easter Island has its origin in French Polynesia.

Thymic pseudotumorous enlargement due to follicular hyperplasia in a human immunodeficiency virus sero-positive patient. Immunohistochemical and molecular biological study of viral infected cells.

PubMed

Prevot, S; Audouin, J; Andre-Bougaran, J; Griffais, R; Le Tourneau, A; Fournier, J G; Diebold, J

1992-03-01

An enlargement of the thymus suggesting a tumor was discovered in a 28-year-old man who had early-stage acquired immune deficiency syndrome. A biopsy was performed. The adipose involuted thymus, with persistence of many Hassall's corpuscles, was judged to be a large lymphoid follicular hyperplasia. This follicular hyperplasia was similar to that previously described for lymph nodes, spleen, and other lymphoid tissues at earlier stages of human immunodeficiency virus infection, before the development of acquired immune deficiency syndrome. Human immunodeficiency virus RNA and p24 human immunodeficiency virus protein were detected in the hyperplastic germinal centers (lymphocytes and follicular dendritic infected cells), and also in many cells that may have been either lymphocytes and/or epithelial cells in the interfollicular areas. The tissue was negative for Epstein-Barr virus DNA sequences, as determined by the polymerase chain reaction. These observations identify the first state of infection of the thymus in a human immune deficiency virus-infected adult, preceding the severe involution with lymphoid depletion observed in all fatal cases of acquired immunodeficiency syndrome in which the thymus has been analyzed.

Diagnosis of Richter transformation in chronic lymphocytic leukemia: histology tips the scales.

PubMed

Federmann, Birgit; Mueller, Martin R; Steinhilber, Julia; Horger, Marius S; Fend, Falko

2018-06-12

Development of diffuse large B-cell lymphoma in chronic lymphocytic leukemia, so-called Richter transformation (RT), occurs in 2-5% of patients and is associated with poor outcome. The clinical features of RT are fairly non-specific and unable to discriminate transformation from other mimics. In case of clinically suspected RT, a CT/MRT is recommended, and FDG-PET/CT may help to select the site of biopsy. Radiological features suggestive of RT have been defined, but there are only limited data about their predictive value, and histological confirmation is still considered the gold standard for RT diagnosis. We retrospectively analyzed 34 patients with clinically suspected RT and available radiological and histological data. A histopathological diagnosis of RT with concordant clinical and radiological findings was obtained in 13 patients. In 18 patients, CT did not show features of transformation, concordant with lack of RT in the biopsy. Of interest, a distinct lymphoma other than DLBCL was identified in two of these cases. A false-positive radiological diagnosis of RT was rendered in two patients, including a case of Herpes simplex virus lymphadenitis. In conclusion, our findings confirm the central role of tissue biopsy in the diagnostic work up in case of clinically suspected RT.

Low Zika virus seroprevalence among pregnant women in North Central Nigeria, 2016.

PubMed

Mathé, Philipp; Egah, Daniel Z; Müller, Janis A; Shehu, Nathan Y; Obishakin, Emmanuel T; Shwe, David D; Pam, Victor C; Okolo, Mark O; Yilgwan, Christopher; Gomerep, Simji S; Fuchs, Jonas; Abok, Ibrahim; Onyedibe, Kenneth I; Olugbo, Ewa J; Isa, Samson E; Machunga-Mambula, Salamatu S; Attah, Caleb J; Münch, Jan; Oguche, Stephen; Panning, Marcus

2018-05-26

Zika virus (ZIKV) has been known for decades in Africa but contemporary data is lacking at large. To describe the seroepidemiology of ZIKV in North Central Nigeria. We performed a cross-sectional study at six health care facilities in North Central Nigeria from January to December 2016. Detection of ZIKV antibodies was done using an anti-ZIKV recombinant non-structural protein 1 (NS1)-based ELISA. A colorimetric assay to detect ZIKV neutralizing antibodies was used on ELISA reactive and randomly selected ELISA non-reactive samples. ZIKV real-time RT-PCR was done on a subset of samples. A total of 468 individual samples were included with almost 60% from pregnant women. Using NS1-based ELISA, an anti-ZIKV positive rate of 6% for IgM and 4% for IgG was found. Pregnant women showed anti-ZIKV positive rates of 4% for IgM and 3% for IgG. None of the ZIKV antibody positive samples tested ZIKV RT-PCR positive. An association with male sex was found for anti-ZIKV IgG ELISA positivity (prevalence ratio 3.49; 95% confidence interval: 1.48-8.25; p = .004). No association with pregnancy, yellow fever vaccination or malaria was found for anti-ZIKV IgM or IgG positivity. ZIKV neutralizing antibodies were detected in 17/18 (94%) anti-ZIKV NS1 positive/borderline samples and in one sample without detectable ZIKV NS1 antibodies. Partial ZIKV E gene sequence was retrieved in one sample without ZIKV antibodies, which clustered within the West African ZIKV lineage. Our results show a largely ZIKV immunologically naïve population and reinforce the importance of ZIKV surveillance in Africa. Copyright © 2018 Elsevier B.V. All rights reserved.

Correlation of human papillomavirus status with apparent diffusion coefficient of diffusion-weighted MRI in head and neck squamous cell carcinomas.

PubMed

Driessen, Juliette P; van Bemmel, Alexander J M; van Kempen, Pauline M W; Janssen, Luuk M; Terhaard, Chris H J; Pameijer, Frank A; Willems, Stefan M; Stegeman, Inge; Grolman, Wilko; Philippens, Marielle E P

2016-04-01

Identification of prognostic patient characteristics in head and neck squamous cell carcinoma (HNSCC) is of great importance. Human papillomavirus (HPV)-positive HNSCCs have favorable response to (chemo)radiotherapy. Apparent diffusion coefficient, derived from diffusion-weighted MRI, has also shown to predict treatment response. The purpose of this study was to evaluate the correlation between HPV status and apparent diffusion coefficient. Seventy-three patients with histologically proven HNSCC were retrospectively analyzed. Mean pretreatment apparent diffusion coefficient was calculated by delineation of total tumor volume on diffusion-weighted MRI. HPV status was analyzed and correlated to apparent diffusion coefficient. Six HNSCCs were HPV-positive. HPV-positive HNSCC showed significantly lower apparent diffusion coefficient compared to HPV-negative. This correlation was independent of other patient characteristics. In HNSCC, positive HPV status correlates with low mean apparent diffusion coefficient. The favorable prognostic value of low pretreatment apparent diffusion coefficient might be partially attributed to patients with a positive HPV status. © 2015 Wiley Periodicals, Inc. Head Neck 38: E613-E618, 2016. © 2015 Wiley Periodicals, Inc.

Challenges for Serology-Based Characterization of Foot-and-Mouth Disease Outbreaks in Endemic Areas; Identification of Two Separate Lineages of Serotype O FMDV in Uganda in 2011.

PubMed

Namatovu, A; Belsham, G J; Ayebazibwe, C; Dhikusooka, M T; Wekesa, S N; Siegismund, H R; Muwanika, V B; Tjørnehøj, K

2015-10-01

Control of foot-and-mouth disease (FMD) in Uganda by ring vaccination largely depends on costly trivalent vaccines, and use of monovalent vaccines could improve the cost effectiveness. This, however, requires application of highly specific diagnostic tests. This study investigated outbreaks of FMD in seven Ugandan districts, during 2011, using the PrioCHECK® FMDV NS ELISA, solid-phase blocking ELISAs (SPBEs) and virus neutralization tests (VNTs), together with virological analyses for characterization of the responsible viruses. Two hundred and eighteen (218) cattle and 23 goat sera as well as 82 oropharyngeal fluid/epithelial tissue samples were collected. Some 50% of the cattle and 17% of the goat sera were positive by the PrioCHECK® FMDV NS ELISA, while SPBEs identified titres ≥80 for antibodies against serotype O FMD virus (FMDV) in 51% of the anti-NSP positive cattle sera. However, 35% of the anti-NSP positive cattle sera had SPBE titres ≥80 against multiple serotypes, primarily against serotypes O, SAT 1 and SAT 3. Comparison of SPBEs and VNTs for the detection of antibodies against serotypes O, SAT 1 and SAT 3 in 72 NSP positive cattle sera showed comparable results against serotype O (P = 0.181), while VNTs detected significantly fewer samples positive for antibodies against SAT 1 and SAT 3 than the SPBEs (P < 0.001). Detection of antibodies against serotype O was consistent with the isolation of serotype O FMDVs from 13 samples. Four of these viruses were sequenced and belonged to two distinct lineages within the East Africa-2 (EA-2) topotype, each differing from the currently used vaccine strain (EA-1 topotype). The relationships of these lineages to other serotype O viruses in the Eastern Africa region are discussed. To enhance the control of FMD in Uganda, there is need to improve the specificity of the SAT-SPBEs, perform vaccine matching and implement improved regional FMD control. © 2013 Blackwell Verlag GmbH.

Effect of Crystal Defects on Minority Carrier Diffusion Length in 6H SiC Measured Using the Electron Beam Induced Current Method

NASA Technical Reports Server (NTRS)

Tabib-Azar, Massood

1997-01-01

We report values of minority carrier diffusion length in n-type 6H SiC measured using a planar Electron Beam Induced Current (EBIC) method. Values of hole diffusion length in defect free regions of n-type 6H SiC, with a doping concentration of 1.7El7 1/cu cm, ranged from 1.46 microns to 0.68 microns. We next introduce a novel variation of the planar method used above. This 'planar mapping' technique measured diffusion length along a linescan creating a map of diffusion length versus position. This map is then overlaid onto the EBIC image of the corresponding linescan, allowing direct visualization of the effect of defects on minority carrier diffusion length. Measurements of the above n-type 6H SiC resulted in values of hole diffusion length ranging from 1.2 micron in defect free regions to below 0.1 gm at the center of large defects. In addition, measurements on p-type 6H SiC resulted in electron diffusion lengths ranging from 1.42 micron to 0.8 micron.

Identification of amino acids of the beet necrotic yellow vein virus p25 protein required for induction of the resistance response in leaves of Beta vulgaris plants.

PubMed

Chiba, Soutaro; Miyanishi, Masaki; Andika, Ida Bagus; Kondo, Hideki; Tamada, Tetsuo

2008-05-01

The RNA3-encoded p25 protein of beet necrotic yellow vein virus (BNYVV) is responsible for the production of rhizomania symptoms of sugar beet roots (Beta vulgaris subsp. vulgaris). Here, it was found that the presence of the p25 protein is also associated with the resistance response in rub-inoculated leaves of sugar beet and wild beet (Beta vulgaris subsp. maritima) plants. The resistance phenotype displayed a range of symptoms from no visible lesions to necrotic or greyish lesions at the inoculation site, and only very low levels of virus and viral RNA accumulated. The susceptible phenotype showed large, bright yellow lesions and developed high levels of virus accumulation. In roots after Polymyxa betae vector inoculation, however, no drastic differences in virus and viral RNA accumulation levels were found between plants with susceptible and resistant phenotypes, except at an early stage of infection. There was a genotype-specific interaction between BNYVV strains and two selected wild beet lines (MR1 and MR2) and sugar beet cultivars. Sequence analysis of natural BNYVV isolates and site-directed mutagenesis of the p25 protein revealed that 3 aa residues at positions 68, 70 and 179 are important in determining the resistance phenotype, and that host-genotype specificity is controlled by single amino acid changes at position 68. The mechanism of the occurrence of resistance-breaking BNYVV strains is discussed.

Treating respiratory viral diseases with chemically modified, second generation intranasal siRNAs.

PubMed

Barik, Sailen

2009-01-01

Chemically synthesized short interfering RNA (siRNA) of pre-determined sequence has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus. As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of intranasal siRNA against RSV, second-generation siRNAs were made against the viral polymerase large subunit (L) that were chemically modified and screened for improved stability, activity and pharmacokinetics. 2'-O-methyl (2'-O-Me) and 2'-deoxy-2'-fluoro (2'-F) substitutions in the ribose ring were incorporated in different positions of the sense and antisense strands and the resultant siRNAs were tested with various transfection reagents intranasally against RSV. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (i) modified 19-27 nt long double-stranded siRNAs are functional in the lung, (ii) excessive 2'-OMe and 2'-F modifications in either or both strands of these siRNAs reduce efficacy, and (iii) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent.

African swine fever outbreak on a medium-sized farm in Uganda: biosecurity breaches and within-farm virus contamination.

PubMed

Chenais, Erika; Sternberg-Lewerin, Susanna; Boqvist, Sofia; Liu, Lihong; LeBlanc, Neil; Aliro, Tonny; Masembe, Charles; Ståhl, Karl

2017-02-01

In Uganda, a low-income country in east Africa, African swine fever (ASF) is endemic with yearly outbreaks. In the prevailing smallholder subsistence farming systems, farm biosecurity is largely non-existent. Outbreaks of ASF, particularly in smallholder farms, often go unreported, creating significant epidemiological knowledge gaps. The continuous circulation of ASF in smallholder settings also creates biosecurity challenges for larger farms. In this study, an on-going outbreak of ASF in an endemic area was investigated on farm level, including analyses of on-farm environmental virus contamination. The study was carried out on a medium-sized pig farm with 35 adult pigs and 103 piglets or growers at the onset of the outbreak. Within 3 months, all pigs had died or were slaughtered. The study included interviews with farm representatives as well as biological and environmental sampling. ASF was confirmed by the presence of ASF virus (ASFV) genomic material in biological (blood, serum) and environmental (soil, water, feed, manure) samples by real-time PCR. The ASFV-positive biological samples confirmed the clinical assessment and were consistent with known virus characteristics. Most environmental samples were found to be positive. Assessment of farm biosecurity, interviews, and the results from the biological and environmental samples revealed that breaches and non-compliance with biosecurity protocols most likely led to the introduction and within-farm spread of the virus. The information derived from this study provides valuable insight regarding the implementation of biosecurity measures, particularly in endemic areas.

Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis.

PubMed

Farinati, F; Cardin, R; De Maria, N; Della Libera, G; Marafin, C; Lecis, E; Burra, P; Floreani, A; Cecchetto, A; Naccarato, R

1995-04-01

Little is known about the pathogenesis of liver damage related to hepatitis C virus. The presence of steatosis or increased ferritin levels, and preliminary data on the relevance of iron as a prognostic factor prompted us to ascertain whether hepatitis C virus-related liver damage might be mediated by iron accumulation. We evaluated the degree of hepatic inflammation and steatosis, serum ferritin, transferrin saturation and iron levels, tissue iron concentrations and iron index, liver glutathione and malondialdehyde in 33 males and 20 females with chronic hepatitis C virus- or hepatitis B virus-related hepatitis (42 + 11). We also considered six patients with both alcohol abuse and hepatitis C virus, four males with chronic alcoholic liver disease and four males with genetic hemochromatosis, giving a total of 67. All diagnoses were histologically confirmed. Patients with cirrhosis were excluded. Our data show that: 1. Steatosis is more frequent in hepatitis C virus and hepatitis C virus+alcohol abuse patients; 2. In males, serum ferritin and tissue iron are significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.01 and 0.05); transferrin saturation is higher (p < 0.05) in hepatitis C virus-positive than in hepatitis B virus-positive patients only when males and females are considered together; 3. Serum ferritin and transferrin saturation only correlate with liver iron (r = 0.833 and r = 0.695, respectively, p = 0.00001); tissue iron is significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.05); 4. In patients with chronic hepatitis, serum ferritin is a better marker of liver iron storage than transferrin saturation, both in males and in females; 5. Hepatitis C virus-positive patients have higher malondialdehyde levels and activation of turnover of glutathione, probably in response to free-radical-mediated liver damage. Females have lower liver iron levels but similar trends. These findings suggest that hepatitis C virus-related liver damage is characterized by increased iron storage (possibly induced by the virus) which elicits a free-radical-mediated peroxidation, with consequent steatosis and activation of glutathione turnover.

Selection of attenuated dengue 4 viruses by serial passage in primary kidney cells. II. Attributes of virus cloned at different dog kidney passage levels.

PubMed

Halstead, S B; Marchette, N J; Diwan, A R; Palumbo, N E; Putvatana, R

1984-07-01

Uncloned dengue (DEN) 4 (H-241) which had been passaged 15, 30 and 50 times in primary dog kidney (PDK) cells were subjected to two successive terminal dilution procedures. In the first (3Cl), virus was diluted in 10-fold steps in 10 replicate tubes. An infected tube from a dilution row with three or fewer virus-infected tubes was selected for two further passages. In the second (TD3), virus was triple terminal diluted using 2-fold dilution steps and selecting one positive tube out of 10. Both procedures selected virus population which differed from antecedents. Plaque size of PDK 15 was medium, PDK 30, small and PDK 50, pin-point. PDK 19-3Cl were medium and 56-3Cl, 24-TD3, 35-TD3 and 61-TD3 were all small. All cloned virus replication was completely shut-off at 38.5 degrees C; PDK 15 and 30 continued to replicate at this temperature. Uncloned viruses showed a graduated decrease in monkey virulence with PDK passage; cloned viruses were either avirulent for monkeys (19-3Cl, 56-31Cl, 24-TD3 and 35-TD3) or produced revertant large plaque parental-type viremia (35-3Cl and 61-TD3). Those cloned viruses which exhibited temperature sensitivity, reduced monkey virulence and stability after monkey passage may be suitable as vaccine candidates for evaluation in human beings.

Zika Virus and Sexual Transmission: A New Route of Transmission for Mosquito-borne Flaviviruses
.

PubMed

Hastings, Andrew K; Fikrig, Erol

2017-06-01

Beginning in 2015, concern over a new global epidemic has spread in the media, governmental agencies, legislative bodies and the public at large. This newly emerging threat has been reported to cause symptoms ranging from mild fever, rash, and body aches, to severe birth defects and acute onset paralysis. The causative agent of this disease, Zika virus, is closely related to two other important human pathogens, dengue and West Nile Virus (WNV), but has some distinguishing features that has raised alarms from the scientific community. Like its two close relatives, this virus is a member of the Flaviviridae family, a class of single stranded RNA viruses with a positive sense genome and is spread primarily via the bite of an infected mosquito. However, this virus has demonstrated another route of transmission that is particularly concerning for people outside of the regions where the main mosquito vector for this virus is present. Sexual transmission of Zika virus has been increasingly reported, from both infected males and females to their partner, which has resulted in the World Health Organization (WHO) and the Center for Disease Control (CDC) issuing warnings to those living in or travelling to areas of Zika transmission to practice abstinence and/or avoid unprotected sexual contact for up to six months after infection with this virus. This perspective will outline the evidence for sexual transmission and persistence of viral infection in semen and vaginal secretions as well as review the animal models for sexual transmission of Zika virus.

Noncoding Subgenomic Flavivirus RNA: Multiple Functions in West Nile Virus Pathogenesis and Modulation of Host Responses

PubMed Central

Roby, Justin A.; Pijlman, Gorben P.; Wilusz, Jeffrey; Khromykh, Alexander A.

2014-01-01

Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA) derived from the 3' untranslated region (UTR). sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'–3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-α/β by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated. PMID:24473339

Biological and Structural Characterization of a Host-Adapting Amino Acid in Influenza Virus

PubMed Central

Yamada, Shinya; Hatta, Masato; Staker, Bart L.; Watanabe, Shinji; Imai, Masaki; Shinya, Kyoko; Sakai-Tagawa, Yuko; Ito, Mutsumi; Ozawa, Makoto; Watanabe, Tokiko; Sakabe, Saori; Li, Chengjun; Kim, Jin Hyun; Myler, Peter J.; Phan, Isabelle; Raymond, Amy; Smith, Eric; Stacy, Robin; Nidom, Chairul A.; Lank, Simon M.; Wiseman, Roger W.; Bimber, Benjamin N.; O'Connor, David H.; Neumann, Gabriele; Stewart, Lance J.; Kawaoka, Yoshihiro

2010-01-01

Two amino acids (lysine at position 627 or asparagine at position 701) in the polymerase subunit PB2 protein are considered critical for the adaptation of avian influenza A viruses to mammals. However, the recently emerged pandemic H1N1 viruses lack these amino acids. Here, we report that a basic amino acid at position 591 of PB2 can compensate for the lack of lysine at position 627 and confers efficient viral replication to pandemic H1N1 viruses in mammals. Moreover, a basic amino acid at position 591 of PB2 substantially increased the lethality of an avian H5N1 virus in mice. We also present the X-ray crystallographic structure of the C-terminus of a pandemic H1N1 virus PB2 protein. Arginine at position 591 fills the cleft found in H5N1 PB2 proteins in this area, resulting in differences in surface shape and charge for H1N1 PB2 proteins. These differences may affect the protein's interaction with viral and/or cellular factors, and hence its ability to support virus replication in mammals. PMID:20700447

An update on vulvar intraepithelial neoplasia: terminology and a practical approach to diagnosis.

PubMed

Reyes, M Carolina; Cooper, Kumarasen

2014-04-01

There are two distinct types of vulvar intraepithelial neoplasia (VIN), which differ in their clinical presentation, aetiology, pathogenesis and histological/immunophenotypical features. One form driven by high-risk human papilloma virus infection usually occurs in young women and has been termed classic or usual VIN (uVIN). The other, not related to viral infection, occurs in postmenopausal women with chronic skin conditions such as lichen sclerosus and lichen simplex chronicus and is termed differentiated or simplex-type VIN. The latter is the precursor lesion of the most common type of squamous cell carcinoma (SCC) in the vulva, namely keratinizing SCC (representing 60% of cases). In contrast, uVIN usually gives rise to basaloid or warty SCC (40% of cases). The histological features of uVIN are similar to those of high grade lesions encountered in other lower anogenital tract sites (hyperchomatic nuclei with high nuclear to cytoplasmic ratios and increased mitotic activity). However, differentiated VIN has very subtle histopathological changes and often escapes diagnosis. Since uVIN is driven by high-risk human papilloma virus infections, p16 immunohistochemistry is diffusely positive in these lesions and is characterized with a high Ki-67 proliferation index. In contrast, differentiated or simplex-type VIN is consistently negative for p16 and the majority of the cases harbour TP53 mutations, correlating with p53 positivity by immunohistochemistry.

Cytologic and immunocytochemical features of EBV negative primary effusion lymphoma: report on seven Japanese cases.

PubMed

Kishimoto, Koji; Kitamura, Takashi; Hirayama, Yoshiko; Tate, Genshu; Mitsuya, Toshiyuki

2009-04-01

Primary effusion lymphoma (PEL) is very rare type of non-Hodgkin's lymphoma (NHL) usually confined to the body cavities such as the pleural space, pericardium, and peritoneum. PEL is a human herpes virus-8 (HHV-8)-associated lymphoma and commonly observed in human immunodeficiency virus (HIV)-infected patients. However, HIV-infected patients are extremely fewer in Japan in comparison with those in Western countries; PEL is usually not associated with HIV infection in Japan. This report presents seven Japanese cases of PEL. In situ hybridization revealed that the PEL cells were negative for EBV in all cases. An immunocytological analysis showed that only one case was positive for HHV-8, and PEL cells were positive for CD20 in all cases. MUM1 was positive, but CD10 and CD138 were negative in six cases. One case each was positive for CD30 and BCL-6. The phenotypic patterns of HIV-related is BCL6-/MUM1+/CD138+, thus, the phenotypic findings observed by immunocytochemistry in this study were somehow different from those reported in Western countries. However, the cytomorphological features of PEL cells showed large cell size, abundant basophilic cytoplasm, coarse chromatin, and occasional binucleated or multinucleated cells, similar to a large cell immunoblastic and anaplastic large cell lymphoma, indicating that the cytomorphological characteristics of PE cells in Giemsa and Papanicolaou stain were consistent with those reported abroad. The prognosis for PEL in these cases was poor, but the survival time was variable ranging from 1 month to 54 months, and was different from that of Western cases. No p16/CDKN2A expression was observed, and one case showed PEL cells with a BLIMP1 mutation.

White matter deficits assessed by diffusion tensor imaging and cognitive dysfunction in psychostimulant users with comorbid human immunodeficiency virus infection.

PubMed

Tang, Victor M; Lang, Donna J; Giesbrecht, Chantelle J; Panenka, William J; Willi, Taylor; Procyshyn, Ric M; Vila-Rodriguez, Fidel; Jenkins, Willough; Lecomte, Tania; Boyda, Heidi N; Aleksic, Ana; MacEwan, G William; Honer, William G; Barr, Alasdair M

2015-09-30

Psychostimulant drug use is commonly associated with drug-related infection, including the human immunodeficiency virus (HIV). Both psychostimulant use and HIV infection are known to damage brain white matter and impair cognition. To date, no study has examined white matter integrity using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) in chronic psychostimulant users with comorbid HIV infection, and determined the relationship of white matter integrity to cognitive function. Twenty-one subjects (mean age 37.5 ± 9.0 years) with a history of heavy psychostimulant use and HIV infection (8.7 ± 4.3 years) and 22 matched controls were scanned on a 3T MRI. Fractional anisotropy (FA) values were calculated with DTI software. Four regions of interest were manually segmented, including the genu of the corpus callosum, left and right anterior limbs of the internal capsule, and the anterior commissure. Subjects also completed a neurocognitive battery and questionnaires about physical and mental health. The psychostimulant using, HIV positive group displayed decreased white matter integrity, with significantly lower FA values for all white matter tracts (p < 0.05). This group also exhibited decreased cognitive performance on tasks that assessed cognitive set-shifting, fine motor speed and verbal memory. FA values for the white matter tracts correlated with cognitive performance on many of the neurocognitive tests. White matter integrity was thus impaired in subjects with psychostimulant use and comorbid HIV infection, which predicted worsened cognitive performance on a range of tests. Further study on this medical comorbidity is required.

Nanotechnology knowledge diffusion: measuring the impact of the research networking and a strategy for improvement

NASA Astrophysics Data System (ADS)

Liu, Xuan; Jiang, Shan; Chen, Hsinchun; Larson, Catherine A.; Roco, Mihail C.

2014-09-01

Given the global increase in public funding for nanotechnology research and development, it is even more important to support projects with promising return on investment. A main return is the benefit to other researchers and to the entire field through knowledge diffusion, invention, and innovation. The social network of researchers is one of the channels through which this happens. This study considers the scientific publication network in the field of nanotechnology, and evaluates how knowledge diffusion through coauthorship and citations is affected in large institutions by the location and connectivity of individual researchers in the network. The relative position and connectivity of a researcher is measured by various social network metrics, including degree centrality, Bonacich Power centrality, structural holes, and betweenness centrality. Leveraging the Cox regression model, we analyzed the temporal relationships between knowledge diffusion and social network measures of researchers in five leading universities in the United States using papers published from 2000 to 2010. The results showed that the most significant effects on knowledge diffusion in the field of nanotechnology were from the structural holes of the network and the degree centrality of individual researchers. The data suggest that a researcher has potential to perform better in knowledge creation and diffusion on boundary-spanning positions between different communities and when he or she has a high level of connectivity in the knowledge network. These observations may lead to improved strategies in planning, conducting, and evaluating multidisciplinary nanotechnology research. The paper also identifies the researchers who made most significant contributions to nanotechnology knowledge diffusion in the networks of five leading U.S. universities.

West Nile Virus in Resident Birds from Yucatan, Mexico.

PubMed

Chaves, Andrea; Sotomayor-Bonilla, Jesus; Monge, Otto; Ramírez, Abigaíl; Galindo, Francisco; Sarmiento-Silva, Rosa Elena; Gutiérrez-Espeleta, Gustavo A; Suzán, Gerardo

2016-01-01

West Nile virus (WNV) in the Americas is thought to be transported at large spatial scales by migratory birds and locally spread and amplified by resident birds. Local processes, including interspecific interactions and dominance of passerine species recognized as competent reservoirs, may boost infection and maintain endemic cycles. Change in species composition has been recognized as an important driver for infection dynamics. Due to migration and changes in species diversity and composition in wintering grounds, changes in infection prevalence are expected. To these changes, we used PCR to estimate the prevalence of WNV in wild resident birds during the dry and rainy seasons of 2012 in Yucatan, Mexico. Serum samples were obtained from 104 wild birds, belonging to six orders and 35 species. We detected WNV in 14 resident birds, representing 11 species and three orders. Prevalences by order was Passeriformes (27%), Columbiformes (6%), and Piciformes (33%). Resident birds positive to WNV from Yucatan may be indicative of local virus circulation and evidence of past virus transmission activity.

Biologically active peptides of the vesicular stomatitis virus glycoprotein.

PubMed Central

Schlegel, R; Wade, M

1985-01-01

A peptide corresponding to the amino-terminal 25 amino acids of the mature vesicular stomatitis virus glycoprotein has recently been shown to be a pH-dependent hemolysin. In the present study, we analyzed smaller constituent peptides and found that the hemolytic domain resides within the six amino-terminal amino acids. Synthesis of variant peptides indicates that the amino-terminal lysine can be replaced by another positively charged amino acid (arginine) but that substitution with glutamic acid results in the total loss of the hemolytic function. Peptide-induced hemolysis was dependent upon buffer conditions and was inhibited when isotonicity was maintained with mannitol, sucrose, or raffinose. In sucrose, all hemolytic peptides were also observed to mediate hemagglutination. The large 25-amino acid peptide is also a pH-dependent cytotoxin for mammalian cells and appears to effect gross changes in cell permeability. Conservation of the amino terminus of vesicular stomatitis virus and rabies virus suggests that the membrane-destabilizing properties of this domain may be important for glycoprotein function. Images PMID:2981356

A New Group of Hepadnaviruses Naturally Infecting Orangutans (Pongo pygmaeus)

PubMed Central

Warren, Kristin S.; Heeney, Jonathan L.; Swan, Ralph A.; Heriyanto; Verschoor, Ernst J.

1999-01-01

A high prevalence (42.6%) of hepatitis B virus (HBV) infection was suspected in 195 formerly captive orangutans due to a large number of serum samples which cross-reacted with human HBV antigens. It was assumed that such viral infections were contracted from humans during captivity. However, two wild orangutans were identified which were HBV surface antigen positive, indicating that HBV or related viruses may be occurring naturally in the orangutan populations. Sequence analyses of seven isolates revealed that orangutans were infected with hepadnaviruses but that these were clearly divergent from the six known human HBV genotypes and those of other nonhuman hepadnaviruses reported. Phylogenetic analyses revealed geographic clustering with Southeast Asian genotype C viruses and gibbon ape HBV. This implies a common origin of infection within this geographic region, with cross-species transmission of hepadnaviruses among hominoids. PMID:10438880

Roles of the phosphorylation of specific serines and threonines in the NS1 protein of human influenza A viruses.

PubMed

Hsiang, Tien-Ying; Zhou, Ligang; Krug, Robert M

2012-10-01

We demonstrate that phosphorylation of the NS1 protein of a human influenza A virus occurs not only at the threonine (T) at position 215 but also at serines (Ss), specifically at positions 42 and 48. By generating recombinant influenza A/Udorn/72 (Ud) viruses that encode mutant NS1 proteins, we determined the roles of these phosphorylations in virus replication. At position 215 only a T-to-A substitution attenuated replication, whereas other substitutions (T to E to mimic constitutive phosphorylation, T to N, and T to P, the amino acid in avian influenza A virus NS1 proteins) had no effect. We conclude that attenuation resulting from the T-to-A substitution at position 215 is attributable to a deleterious structural change in the NS1 protein that is not caused by other amino acid substitutions and that phosphorylation of T215 does not affect virus replication. At position 48 neither an S-to-A substitution nor an S-to-D substitution that mimics constitutive phosphorylation affected virus replication. In contrast, at position 42, an S-to-D, but not an S-to-A, substitution caused attenuation. The S-to-D substitution eliminates detectable double-stranded RNA binding by the NS1 protein, accounting for attenuation of virus replication. We show that protein kinase C α (PKCα) catalyzes S42 phosphorylation. Consequently, the only phosphorylation of the NS1 protein of this human influenza A virus that regulates its replication is S42 phosphorylation catalyzed by PKCα. In contrast, phosphorylation of Ts or Ss in the NS1 protein of the 2009 H1N1 pandemic virus was not detected, indicating that NS1 phosphorylation probably does not play any role in the replication of this virus.

Temperature Dependence of Nonelectrolyte Permeation across Red Cell Membranes

PubMed Central

Galey, W. R.; Owen, J. D.; Solomon, A. K.

1973-01-01

The temperature dependence of permeation across human red cell membranes has been determined for a series of hydrophilic and lipophilic solutes, including urea and two methyl substituted derivatives, all the straight-chain amides from formamide through valeramide and the two isomers, isobutyramide and isovaleramide. The temperature coefficient for permeation by all the hydrophilic solutes is 12 kcal mol-1 or less, whereas that for all the lipophilic solutes is 19 kcal mol-1 or greater. This difference is consonant with the view that hydrophilic molecules cross the membrane by a path different from that taken by the lipophilic ones. The thermodynamic parameters associated with lipophile permeation have been studied in detail. ΔG is negative for adsorption of lipophilic amides onto an oil-water interface, whereas it is positive for transfer of the polar head from the aqueous medium to bulk lipid solvent. Application of absolute reaction rate theory makes it possible to make a clear distinction between diffusion across the water-red cell membrane interface and diffusion within the membrane. Diffusion coefficients and apparent activation enthalpies and entropies have been computed for each process. Transfer of the polar head from the solvent into the interface is characterized by ΔG ‡ = 0 kcal mol-1 and ΔS ‡ negative, whereas both of these parameters have large positive values for diffusion within the membrane. Diffusion within the membrane is similar to what is expected for diffusion through a highly associated viscous fluid. PMID:4708405

Comparison of Test Results for Zika Virus RNA in Urine, Serum, and Saliva Specimens from Persons with Travel-Associated Zika Virus Disease - Florida, 2016.

PubMed

Bingham, Andrea M; Cone, Marshall; Mock, Valerie; Heberlein-Larson, Lea; Stanek, Danielle; Blackmore, Carina; Likos, Anna

2016-05-13

In May 2015, Zika virus was reported to be circulating in Brazil. This was the first identified introduction of the virus in the Region of the Americas. Since that time, Zika virus has rapidly spread throughout the region. As of April 20, 2016, the Florida Department of Health Bureau of Public Health Laboratories (BPHL) has tested specimens from 913 persons who met state criteria for Zika virus testing. Among these 913 persons, 91 met confirmed or probable Zika virus disease case criteria and all cases were travel-associated (1). On the basis of previous small case studies reporting real time reverse-transcription polymerase chain reaction (RT-PCR) detection of Zika virus RNA in urine, saliva, and semen (2-6), the Florida Department of Health collected multiple specimen types from persons with suspected Zika virus disease. Test results were evaluated by specimen type and number of days after symptom onset to determine the most sensitive and efficient testing algorithm for acute Zika virus disease. Urine specimens were collected from 70 patients with suspected Zika virus disease from zero to 20 days after symptom onset. Of these, 65 (93%) tested positive for Zika virus RNA by RT-PCR. Results for 95% (52/55) of urine specimens collected from persons within 5 days of symptom onset tested positive by RT-PCR; only 56% (31/55) of serum specimens collected on the same date tested positive by RT-PCR. Results for 82% (9/11) of urine specimens collected >5 days after symptom onset tested positive by RT-PCR; none of the RT-PCR tests for serum specimens were positive. No cases had results that were exclusively positive by RT-PCR testing of saliva. BPHL testing results suggest urine might be the preferred specimen type to identify acute Zika virus disease.

Systematic CpT (ApG) Depletion and CpG Excess Are Unique Genomic Signatures of Large DNA Viruses Infecting Invertebrates

PubMed Central

Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal

2014-01-01

Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts. PMID:25369195

Efficiency in Complexity: Composition and Dynamic Nature of Mimivirus Replication Factories

PubMed Central

Milrot, Elad; Mutsafi, Yael; Ben-Dor, Shifra; Levin, Yishai; Savidor, Alon; Kartvelishvily, Elena

2016-01-01

ABSTRACT The recent discovery of multiple giant double-stranded DNA (dsDNA) viruses blurred the consensual distinction between viruses and cells due to their size, as well as to their structural and genetic complexity. A dramatic feature revealed by these viruses as well as by many positive-strand RNA viruses is their ability to rapidly form elaborate intracellular organelles, termed “viral factories,” where viral progeny are continuously generated. Here we report the first isolation of viral factories at progressive postinfection time points. The isolated factories were subjected to mass spectrometry-based proteomics, bioinformatics, and imaging analyses. These analyses revealed that numerous viral proteins are present in the factories but not in mature virions, thus implying that multiple and diverse proteins are required to promote the efficiency of viral factories as “production lines” of viral progeny. Moreover, our results highlight the dynamic and highly complex nature of viral factories, provide new and general insights into viral infection, and substantiate the intriguing notion that viral factories may represent the living state of viruses. IMPORTANCE Large dsDNA viruses such as vaccinia virus and the giant mimivirus, as well as many positive-strand RNA viruses, generate elaborate cytoplasmic organelles in which the multiple and diverse transactions required for viral replication and assembly occur. These organelles, which were termed “viral factories,” are attracting much interest due to the increasing realization that the rapid and continuous production of viral progeny is a direct outcome of the elaborate structure and composition of the factories, which act as efficient production lines. To get new insights into the nature and function of viral factories, we devised a method that allows, for the first time, the isolation of these organelles. Analyses of the isolated factories generated at different times postinfection by mass spectrometry-based proteomics provide new perceptions of their role and reveal the highly dynamic nature of these organelles. PMID:27581975

Pre- Versus Posttransplant Treatment of Hepatitis C Virus With Direct-Acting Antivirals in Liver Transplant Recipients: More Issues to be Solved.

PubMed

Abdelqader, Abdelhai; Kabacam, Gokhan; Woreta, Tinsay A; Hamilton, James P; Luu, Harry; Al Khalloufi, Kawtar; Saberi, Behnam; Philosophe, Benjamin; Cameron, Andrew M; Gurakar, Ahmet

2017-02-01

Our goal was to investigate wait times related to hepatitis C virus treatment with direct acting antivirals before versus after liver transplant at a single center as well as wait times for insurance approval for preemptive treatment with these agents after liver transplant. We retrospectively evaluated hepatitis C virus infections in transplant recipients of deceased liver donations in 2014 and 2015. Demographics, hepatocellular carcinoma incidence, Model for End-Stage Liver Disease scores, and transplant wait times were compared between patients treated before or after liver transplant. Wait times to approval of direct-acting antiviral treatment were evaluated in those untreated before transplant. During our study period, of 67 deceased-donor liver transplants, 21 patients received hepatitis C virus treatment pretransplant (treated group) and 46 patients were not treated pretransplant (untreated group). Twenty-five patients in the untreated group received hepatitis C virus-positive donations, with all in this group treated with direct-acting antivirals. We found no statistically significant differences regarding age, sex, race, donation after cardiac death, or incidence of hepatocellular carcinoma between groups. The treated group had a longer median wait time (287 vs 172 days; P = .02). Twelve of the 46 untreated patients (26.1%) developed biopsy-proven hepatitis C virus-related relapse (median 87 days; range, 55-383 days). Preemptive direct-acting antiviral therapy was initiated at a median of 81 days in the untreated group. Although treatment of hepatitis C virus before liver transplant is an attractive option to eliminate the risk of complications, it can limit the donor pool for recipients to uninfected donors, significantly increasing wait times in regions with large hepatitis C virus-positive donor pools. Allocation of Model for End-Stage Liver Disease score was not different between the treated and untreated groups. Insurance companies should revise their policies for rapid approval of preemptive direct-acting antiviral treatment after liver transplant.

Validation of a Computational Model for the SLS Core Stage Oxygen Tank Diffuser Concept and the Low Profile Diffuser - An Advanced Development Design for the SLS

NASA Technical Reports Server (NTRS)

Brodnick, Jacob; Richardson, Brian; Ramachandran, Narayanan

2015-01-01

The Low Profile Diffuser (LPD) project originated as an award from the Marshall Space Flight Center (MSFC) Advanced Development (ADO) office to the Main Propulsion Systems Branch (ER22). The task was created to develop and test an LPD concept that could produce comparable performance to a larger, traditionally designed, ullage gas diffuser while occupying a smaller volume envelope. Historically, ullage gas diffusers have been large, bulky devices that occupy a significant portion of the propellant tank, decreasing the tank volume available for propellant. Ullage pressurization of spacecraft propellant tanks is required to prevent boil-off of cryogenic propellants and to provide a positive pressure for propellant extraction. To achieve this, ullage gas diffusers must slow hot, high-pressure gas entering a propellant tank from supersonic speeds to only a few meters per second. Decreasing the incoming gas velocity is typically accomplished through expansion to larger areas within the diffuser which has traditionally led to large diffuser lengths. The Fluid Dynamics Branch (ER42) developed and applied advanced Computational Fluid Dynamics (CFD) analysis methods in order to mature the LPD design from and initial concept to an optimized test prototype and to provide extremely accurate pre-test predictions of diffuser performance. Additionally, the diffuser concept for the Core Stage of the Space Launch System (SLS) was analyzed in a short amount of time to guide test data collection efforts of the qualification of the device. CFD analysis of the SLS diffuser design provided new insights into the functioning of the device and was qualitatively validated against hot wire anemometry of the exterior flow field. Rigorous data analysis of the measurements was performed on static and dynamic pressure data, data from two microphones, accelerometers and hot wire anemometry with automated traverse. Feasibility of the LPD concept and validation of the computational model were demonstrated by the test data.

Specific Antibodies Reacting with SV40 Large T Antigen Mimotopes in Serum Samples of Healthy Subjects

PubMed Central

Tognon, Mauro; Corallini, Alfredo; Manfrini, Marco; Taronna, Angelo; Butel, Janet S.; Pietrobon, Silvia; Trevisiol, Lorenzo; Bononi, Ilaria; Vaccher, Emanuela; Barbanti-Brodano, Giuseppe; Martini, Fernanda; Mazzoni, Elisa

2016-01-01

Simian Virus 40, experimentally assayed in vitro in different animal and human cells and in vivo in rodents, was classified as a small DNA tumor virus. In previous studies, many groups identified Simian Virus 40 sequences in healthy individuals and cancer patients using PCR techniques, whereas others failed to detect the viral sequences in human specimens. These conflicting results prompted us to develop a novel indirect ELISA with synthetic peptides, mimicking Simian Virus 40 capsid viral protein antigens, named mimotopes. This immunologic assay allowed us to investigate the presence of serum antibodies against Simian Virus 40 and to verify whether Simian Virus 40 is circulating in humans. In this investigation two mimotopes from Simian Virus 40 large T antigen, the viral replication protein and oncoprotein, were employed to analyze for specific reactions to human sera antibodies. This indirect ELISA with synthetic peptides from Simian Virus 40 large T antigen was used to assay a new collection of serum samples from healthy subjects. This novel assay revealed that serum antibodies against Simian Virus 40 large T antigen mimotopes are detectable, at low titer, in healthy subjects aged from 18–65 years old. The overall prevalence of reactivity with the two Simian Virus 40 large T antigen peptides was 20%. This new ELISA with two mimotopes of the early viral regions is able to detect in a specific manner Simian Virus 40 large T antigen-antibody responses. PMID:26731525

Diffuse Surface Scattering in the Plasmonic Resonances of Ultralow Electron Density Nanospheres.

PubMed

Monreal, R Carmina; Antosiewicz, Tomasz J; Apell, S Peter

2015-05-21

Localized surface plasmon resonances (LSPRs) have recently been identified in extremely diluted electron systems obtained by doping semiconductor quantum dots. Here, we investigate the role that different surface effects, namely, electronic spill-out and diffuse surface scattering, play in the optical properties of these ultralow electron density nanosystems. Diffuse scattering originates from imperfections or roughness at a microscopic scale on the surface. Using an electromagnetic theory that describes this mechanism in conjunction with a dielectric function including the quantum size effect, we find that the LSPRs show an oscillatory behavior in both position and width for large particles and a strong blue shift in energy and an increased width for smaller radii, consistent with recent experimental results for photodoped ZnO nanocrystals. We thus show that the commonly ignored process of diffuse surface scattering is a more important mechanism affecting the plasmonic properties of ultralow electron density nanoparticles than the spill-out effect.

Differential gene expression in HIV/SIV-associated and spontaneous lymphomas

PubMed Central

2005-01-01

Diffuse large B-cell lymphoma (DLBCL) is more prevalent and more often fatal in HIV-infected patients and SIV-infected monkeys compared to immune-competent individuals. Molecular, biological, and immunological data indicate that virus-associated lymphomagenesis is similar in both infected hosts. To find genes specifically overexpressed in HIV/SIV-associated and non-HIV/SIV-associated DLBCL we compared gene expression profiles of HIV/SIV-related and non-HIV-related lymphomas using subtractive hybridization and Northern blot analysis. Our experimental approach allowed us to detect two genes (a-myb and pub) upregulated solely in HIV/SIV-associated DLBCLs potentially involved in virus-specific lymphomagenesis in human and monkey. Downregulation of the pub gene was observed in all non-HIV-associated lymphomas investigated. In addition, we have found genes upregulated in both non-HIV- and HIV-associated lymphomas. Among those were genes both with known (set, ND4, SMG-1) and unknown functions. In summary, we have demonstrated that simultaneous transcriptional upregulation of at least two genes (a-myb and pub) was specific for AIDS-associated lymphomas. PMID:16239949

Hemophagocytic lymphohistiocytosis caused by primary Epstein-Barr virus in patient with Crohn's disease.

PubMed

Virdis, Francesco; Tacci, Sara; Messina, Federico; Varcada, Massimo

2013-11-27

We present a case of a 19-year-old man with a 6-year history of Crohn's disease (CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus (EBV) infection and subsequently developed a hemophagocytic lymphohistiocytosis (HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EBV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease (IBD) treated with thiopurines. Specific EBV-related clinical and virological management should be considered when treating a patient with IBD with immunosuppressive therapy. Moreover EBV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large B cell lymphoma. Our case confirms what is described in the literature; patients with IBD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH.

Hepatitis C Virus-Related Lymphomagenesis in a Mouse Model

PubMed Central

Tsukiyama-Kohara, Kyoko; Sekiguchi, Satoshi; Kasama, Yuri; Salem, Nagla Elwy; Machida, Keigo; Kohara, Michinori

2011-01-01

B cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with hepatitis C virus (HCV) infection. The mechanism by which HCV infection leads to lymphoproliferative disorder remains unclear. Our group established HCV transgenic mice that expressed the full HCV genome in B cells (RzCD19Cre mice). We observed a 25.0% incidence of diffuse large B cell non-Hodgkin lymphomas (22.2% in male and 29.6% in female mice) within 600 days of birth. Interestingly, RzCD19Cre mice with substantially elevated serum-soluble interleukin-2 receptor α-subunit (sIL-2Rα) levels (>1000 pg/mL) developed B cell lymphomas. Another mouse model of lymphoproliferative disorder was established by persistent expression of HCV structural proteins through disruption of interferon regulatory factor-1 (irf-1_/_/CN2 mice). Irf-1_/_/CN2 mice showed extremely high incidences of lymphomas and lymphoproliferative disorders. Moreover, these mice showed increased levels of interleukin (IL)-2, IL-10, and Bcl-2 as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes. PMID:22084693

[Risk related to the transmission of H5N1 subtype avian influenza virus in the environment of poultry markets in Changsha, China].

PubMed

Zhang, Ru-sheng; Ou, Xin-hua; Song, Ke-yun; Yuan, Jie; Chen, Tian-mu; Xiao, Shan; Sun, Bian-cheng

2012-08-01

To investigate the risk of H5N1 subtype avian influenza virus (AIV) transmission in the poultry market environment in Changsha city. H5N1 antibody levels among the groups related occupational exposure and AIV nucleic acid in the environment of poultry markets were detected. The characteristics of haemagglutinin (HA) genes of H5N1 AIV in the environment were analyzed. One district and one county from Changsha city were selected randomly and two poultry markets at inner city or township levels were selected in the same district or county respectively. H5N1 antibody of the occupational exposure groups in the poultry market was tested and AIV nucleic acid in the poultry market environment monitored. One hundred and two blood samples of the occupational exposure groups were tested for H5N1 antibody with single radioimmunoassay diffusion hemolysis (SRH) while 160 environment samples (from sewage, birds stools, feathers and smearing samples of poultry cages) in the poultry market were also detected for AIV nucleic acid with real-time PCR method. Four sewage samples of H5N1 subtype AIV were collected from poultry markets in Changsha, and the HA genes of H5N1 subtype AIV amplified by RT-PCR and then sequenced with TA cloning. Amino acid sequence alignment and phylogenetic tree analysis were conducted by Lasergene and Mega 5.0 software. The results through H5N1 antibody monitoring program showed that H5N1 antibody positive rates from workers were 25.5% (26/102), 50.0% (9/18) and 25.4% (17/67) respectively in the poultry markets of township and inner cities. H5N1 antibody positive rate in the township poultry markets was higher than in the inner cities poultry markets. from the surveillance on AIV nucleic acid showed that the overall H5 subtype positive rate in Changsha poultry markets was 31.3% (50/160), and the positive rate of townships poultry markets was 37.3% (31/83), which were both higher than those from the inner cities poultry markets (24.7%, 19/77). H5 subtype AIV positive rate was different in the tested specimens, with ranking of positive rates were sewage (50.0%, 24/48), feathers (44.5%, 4/9), birds stools (29.8%, 14/47) and smearing samples of poultry cages (14.3%, 8/56), with statistically significant differences (P < 0.01). Four H5N1 HA genes TA cloning were successfully constructed and identified as Eurasian branch, similar to viruses isolated in mainland China and Hong Kong in the same group, according to genetic analysis. Sequence data of the four HA genes showed the same feature of high pathogenicity, compared to the H5N1 AIV from mainland China of human origin. The receptor specificities were still with avian influenza origin (QSG) and the connecting peptide between HA1 and HA2 possessing the polybasic motif (RERRRKK or RERRGKK). One of the reasons for H5N1 antibody positive rate of 25.5% among poultry markets workers was that there were large numbers of H5N1 subtype AIV detected in the environment of poultry markets and HA genes of H5N1 subtype AIV in the poultry markets environment carried molecular characteristics of highly pathogenic which could increase the risk for H5N1 subtype AIV transmission in the environment of poultry markets.

PB2 mutations D701N and S714R promote adaptation of an influenza H5N1 virus to a mammalian host.

PubMed

Czudai-Matwich, Volker; Otte, Anna; Matrosovich, Mikhail; Gabriel, Gülsah; Klenk, Hans-Dieter

2014-08-01

Mutation D701N in the PB2 protein is known to play a prominent role in the adaptation of avian influenza A viruses to mammalian hosts. In contrast, little is known about the nearby mutations S714I and S714R, which have been observed in some avian influenza viruses highly pathogenic for mammals. We have generated recombinant H5N1 viruses with PB2 displaying the avian signature 701D or the mammalian signature 701N and serine, isoleucine, and arginine at position 714 and compared them for polymerase activity and virus growth in avian and mammalian cells, as well as for pathogenicity in mice. Mutation D701N led to an increase in polymerase activity and replication efficiency in mammalian cells and in mouse pathogenicity, and this increase was significantly enhanced when mutation D701N was combined with mutation S714R. Stimulation by mutation S714I was less distinct. These observations indicate that PB2 mutation S714R, in combination with the mammalian signature at position 701, has the potential to promote the adaptation of an H5N1 virus to a mammalian host. Influenza A/H5N1 viruses are avian pathogens that have pandemic potential, since they are spread over large parts of Asia, Africa, and Europe and are occasionally transmitted to humans. It is therefore of high scientific interest to understand the mechanisms that determine the host specificity and pathogenicity of these viruses. It is well known that the PB2 subunit of the viral polymerase is an important host range determinant and that PB2 mutation D701N plays an important role in virus adaptation to mammalian cells. In the present study, we show that mutation S714R is also involved in adaptation and that it cooperates with D701N in exposing a nuclear localization signal that mediates importin-α binding and entry of PB2 into the nucleus, where virus replication and transcription take place. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Hepatitis delta virus infection in a large cohort of chronic hepatitis B patients in Ethiopia.

PubMed

Aberra, Hanna; Gordien, Emmanuel; Desalegn, Hailemichael; Berhe, Nega; Medhin, Girmay; Mekasha, Bitsatab; Gundersen, Svein G; Gerber, Athenaïs; Stene-Johansen, Kathrine; Øverbø, Joakim; Johannessen, Asgeir

2018-06-01

Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia. In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA-positive samples by nucleotide sequencing followed by phylogenetic analyses. Demographical, clinical and biological data from patients were recorded and compared based on HDV RNA results. Most patients (n = 748, 59.0%) were men, and the median age was 31 years (interquartile range 26-40). Anti-HDV antibodies were detected in 19 individuals (1.5%), 12 of whom were HDV RNA-positive with a viral load ranging from <2 to >8 log 10 IU/mL. All strains were genotype 1. HDV RNA-positive patients were more likely to have significant liver fibrosis (63.6% vs 24.7%, P = .007) and cirrhosis (45.5% vs 16.4%, P = .024). HDV infection is rare in Ethiopia but is associated with more advanced liver fibrosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Kinetic Monte Carlo Simulation of Oxygen Diffusion in Ytterbium Disilicate

NASA Technical Reports Server (NTRS)

Good, Brian S.

2015-01-01

Ytterbium disilicate is of interest as a potential environmental barrier coating for aerospace applications, notably for use in next generation jet turbine engines. In such applications, the transport of oxygen and water vapor through these coatings to the ceramic substrate is undesirable if high temperature oxidation is to be avoided. In an effort to understand the diffusion process in these materials, we have performed kinetic Monte Carlo simulations of vacancy-mediated and interstitial oxygen diffusion in Ytterbium disilicate. Oxygen vacancy and interstitial site energies, vacancy and interstitial formation energies, and migration barrier energies were computed using Density Functional Theory. We have found that, in the case of vacancy-mediated diffusion, many potential diffusion paths involve large barrier energies, but some paths have barrier energies smaller than one electron volt. However, computed vacancy formation energies suggest that the intrinsic vacancy concentration is small. In the case of interstitial diffusion, migration barrier energies are typically around one electron volt, but the interstitial defect formation energies are positive, with the result that the disilicate is unlikely to exhibit experience significant oxygen permeability except at very high temperature.

Unilateral uveitis masquerade syndrome caused by diffuse large B-cell lymphoma diagnosed using multiparametric flow cytometry of the aqueous humor.

PubMed

Monsalvo, Silvia; Serrano, Cristina; Prieto, Elena; Fernández-Sanz, Guillermo; Puente, Maria-Camino; Rodriguez-Pinilla, Maria; Garcia Raso, Aranzazu; Llamas, Pilar; Cordoba, Raul

2017-07-01

The uveitis masquerade syndromes (UMS) are a group of ocular diseases that may mimic chronic intraocular inflammation. Many malignant entities such as non-Hodgkin's lymphomas may masquerade as uveitis. We report a case of an HIV-positive patient with masquerade syndrome presenting unilateral uveitis. 45-year-old Caucasian man with a diagnosis of diffuse large B-cell lymphoma (DLBCL). The patient was diagnosed by a biopsy of an abdominal mass which showed fragments of gastric mucosa with diffuse growth of neoplastic cells. At diagnosis, the patient suffered from unilateral blurring of vision and a sudden decrease of left-eye visual acuity. A slit-lamp examination of the left eye revealed a diagnosis of anterior uveitis. The patient exhibited no signs of posterior uveitis. An anterior-chamber paracentesis was performed and analyzed by multiparameter flow cytometry (MFC), showing cells CD45, CD19, CD20, CD22, and CD38 positives, and moderate expression of CD10 with kappa light chain restriction, showing a monoclonal B-cell population. The patient received CHOP-R with intrathecal methotrexate followed by consolidation high dose methotrexate obtaining a complete response which is ongoing. Differential diagnosis between chronic uveitis and ocular lymphoma may be challenging. We advocate anterior-chamber paracentesis in cases of refractory uveitis in patients with hematologic malignancies. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

Stem water storage in five coexisting temperate broad-leaved tree species: significance, temporal dynamics and dependence on tree functional traits.

PubMed

Köcher, Paul; Horna, Viviana; Leuschner, Christoph

2013-08-01

The functional role of internal water storage is increasingly well understood in tropical trees and conifers, while temperate broad-leaved trees have only rarely been studied. We examined the magnitude and dynamics of the use of stem water reserves for transpiration in five coexisting temperate broad-leaved trees with largely different morphology and physiology (genera Fagus, Fraxinus, Tilia, Carpinus and Acer). We expected that differences in water storage patterns would mostly reflect species differences in wood anatomy (ring vs. diffuse-porous) and wood density. Sap flux density was recorded synchronously at five positions along the root-to-branch flow path of mature trees (roots, three stem positions and branches) with high temporal resolution (2 min) and related to stem radius changes recorded with electronic point dendrometers. The daily amount of stored stem water withdrawn for transpiration was estimated by comparing the integrated flow at stem base and stem top. The temporal coincidence of flows at different positions and apparent time lags were examined by cross-correlation analysis. Our results confirm that internal water stores play an important role in the four diffuse-porous species with estimated 5-12 kg day(-1) being withdrawn on average in 25-28 m tall trees representing 10-22% of daily transpiration; in contrast, only 0.5-2.0 kg day(-1) was withdrawn in ring-porous Fraxinus. Wood density had a large influence on storage; sapwood area (diffuse- vs. ring-porous) may be another influential factor but its effect was not significant. Across the five species, the length of the time lag in flow at stem top and stem base was positively related to the size of stem storage. The stem stores were mostly exhausted when the soil matrix potential dropped below -0.1 MPa and daily mean vapor pressure deficit exceeded 3-5 hPa. We conclude that stem storage is an important factor improving the water balance of diffuse-porous temperate broad-leaved trees in moist periods, while it may be of low relevance in dry periods and in ring-porous species.

CD4 T cell decline following HIV seroconversion in individuals with and without CXCR4-tropic virus.

PubMed

Ghosn, Jade; Bayan, Tatiana; Meixenberger, Karolin; Tran, Laurent; Frange, Pierre; d'Arminio Monforte, Antonella; Zangerle, Robert; de Mendoza, Carmen; Krastinova, Evguenia; Porter, Kholoud; Meyer, Laurence; Chaix, Marie-Laure

2017-10-01

The natural clinical and immunological courses following HIV seroconversion with CXCR4-tropic or dual-mixed (X4/DM) viruses are controversial. We compared spontaneous immunological outcome in patients harbouring an X4/DM virus at the time of seroconversion with those harbouring a CCR5-tropic (R5) virus. Data were included from patients participating in CASCADE, a large cohort collaboration of HIV seroconverters, with ≥2 years of follow-up since seroconversion. The HIV envelope gene was sequenced from frozen plasma samples collected at enrolment, and HIV tropism was determined using Geno2Pheno (false-positive rate 10%). The spontaneous CD4 T cell evolution was compared by modelling CD4 kinetics using linear mixed-effects models with random intercept and random slope. A total of 1387 patients were eligible. Median time between seroconversion and enrolment was 1 month (range 0-3). At enrolment, 202 of 1387 (15%) harboured an X4/DM-tropic virus. CD4 decrease slopes were not significantly different according to HIV-1 tropism during the first 30 months after seroconversion. No marked change in these results was found after adjusting for age, year of seroconversion and baseline HIV viral load. Time to antiretroviral treatment initiation was not statistically different between patients harbouring an R5 (20.76 months) and those harbouring an X4/DM-tropic virus (22.86 months, logrank test P = 0.32). Conclusions: In this large cohort collaboration, 15% of the patients harboured an X4/DM virus close to HIV seroconversion. Patients harbouring X4/DM-tropic viruses close to seroconversion did not have an increased risk of disease progression, estimated by the decline in CD4 T cell count or time to combined ART initiation. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Revisiting the immune microenvironment of diffuse large B-cell lymphoma using a tissue microarray and immunohistochemistry: robust semi-automated analysis reveals CD3 and FoxP3 as potential predictors of response to R-CHOP

PubMed Central

Coutinho, Rita; Clear, Andrew J.; Mazzola, Emanuele; Owen, Andrew; Greaves, Paul; Wilson, Andrew; Matthews, Janet; Lee, Abigail; Alvarez, Rute; da Silva, Maria Gomes; Cabeçadas, José; Neuberg, Donna; Calaminici, Maria; Gribben, John G.

2015-01-01

Gene expression studies have identified the microenvironment as a prognostic player in diffuse large B-cell lymphoma. However, there is a lack of simple immune biomarkers that can be applied in the clinical setting and could be helpful in stratifying patients. Immunohistochemistry has been used for this purpose but the results are inconsistent. We decided to reinvestigate the immune microenvironment and its impact using immunohistochemistry, with two systems of image analysis, in a large set of patients with diffuse large B-cell lymphoma. Diagnostic tissue from 309 patients was arrayed onto tissue microarrays. Results from 161 chemoimmunotherapy-treated patients were used for outcome prediction. Positive cells, percentage stained area and numbers of pixels/area were quantified and results were compared with the purpose of inferring consistency between the two semi-automated systems. Measurement cutpoints were assessed using a recursive partitioning algorithm classifying results according to survival. Kaplan-Meier estimators and Fisher exact tests were evaluated to check for significant differences between measurement classes, and for dependence between pairs of measurements, respectively. Results were validated by multivariate analysis incorporating the International Prognostic Index. The concordance between the two systems of image analysis was surprisingly high, supporting their applicability for immunohistochemistry studies. Patients with a high density of CD3 and FoxP3 by both methods had a better outcome. Automated analysis should be the preferred method for immunohistochemistry studies. Following the use of two methods of semi-automated analysis we suggest that CD3 and FoxP3 play a role in predicting response to chemoimmunotherapy in diffuse large B-cell lymphoma. PMID:25425693

Revisiting the immune microenvironment of diffuse large B-cell lymphoma using a tissue microarray and immunohistochemistry: robust semi-automated analysis reveals CD3 and FoxP3 as potential predictors of response to R-CHOP.

PubMed

Coutinho, Rita; Clear, Andrew J; Mazzola, Emanuele; Owen, Andrew; Greaves, Paul; Wilson, Andrew; Matthews, Janet; Lee, Abigail; Alvarez, Rute; da Silva, Maria Gomes; Cabeçadas, José; Neuberg, Donna; Calaminici, Maria; Gribben, John G

2015-03-01

Gene expression studies have identified the microenvironment as a prognostic player in diffuse large B-cell lymphoma. However, there is a lack of simple immune biomarkers that can be applied in the clinical setting and could be helpful in stratifying patients. Immunohistochemistry has been used for this purpose but the results are inconsistent. We decided to reinvestigate the immune microenvironment and its impact using immunohistochemistry, with two systems of image analysis, in a large set of patients with diffuse large B-cell lymphoma. Diagnostic tissue from 309 patients was arrayed onto tissue microarrays. Results from 161 chemoimmunotherapy-treated patients were used for outcome prediction. Positive cells, percentage stained area and numbers of pixels/area were quantified and results were compared with the purpose of inferring consistency between the two semi-automated systems. Measurement cutpoints were assessed using a recursive partitioning algorithm classifying results according to survival. Kaplan-Meier estimators and Fisher exact tests were evaluated to check for significant differences between measurement classes, and for dependence between pairs of measurements, respectively. Results were validated by multivariate analysis incorporating the International Prognostic Index. The concordance between the two systems of image analysis was surprisingly high, supporting their applicability for immunohistochemistry studies. Patients with a high density of CD3 and FoxP3 by both methods had a better outcome. Automated analysis should be the preferred method for immunohistochemistry studies. Following the use of two methods of semi-automated analysis we suggest that CD3 and FoxP3 play a role in predicting response to chemoimmunotherapy in diffuse large B-cell lymphoma. Copyright© Ferrata Storti Foundation.

Preliminary crystallographic analysis of the major capsid protein P2 of the lipid-containing bacteriophage PM2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abrescia, Nicola G. A.; Kivelä, Hanna M.; Grimes, Jonathan M.

2005-08-01

The viral capsid protein P2 of bacteriophage PM2 has been crystallized. Preliminary X-ray analysis demonstrates the position and orientation of the two trimers in the asymmetric unit. PM2 (Corticoviridae) is a dsDNA bacteriophage which contains a lipid membrane beneath its icosahedral capsid. In this respect it resembles bacteriophage PRD1 (Tectiviridae), although it is not known whether the similarity extends to the detailed molecular architecture of the virus, for instance the fold of the major coat protein P2. Structural analysis of PM2 has been initiated and virus-derived P2 has been crystallized by sitting-nanodrop vapour diffusion. Crystals of P2 have been obtainedmore » in space group P2{sub 1}2{sub 1}2, with two trimers in the asymmetric unit and unit-cell parameters a = 171.1, b = 78.7, c = 130.1 Å. The crystals diffract to 4 Å resolution at the ESRF BM14 beamline (Grenoble, France) and the orientation of the non-crystallographic threefold axes, the spatial relationship between the two trimers and the packing of the trimers within the unit cell have been determined. The trimers form tightly packed layers consistent with the crystal morphology, possibly recapitulating aspects of the arrangement of subunits in the virus.« less

Structure of large dsDNA viruses

PubMed Central

Klose, Thomas; Rossmann, Michael G.

2015-01-01

Nucleocytoplasmic large dsDNA viruses (NCLDVs) encompass an ever-increasing group of large eukaryotic viruses, infecting a wide variety of organisms. The set of core genes shared by all these viruses includes a major capsid protein with a double jelly-roll fold forming an icosahedral capsid, which surrounds a double layer membrane that contains the viral genome. Furthermore, some of these viruses, such as the members of the Mimiviridae and Phycodnaviridae have a unique vertex that is used during infection to transport DNA into the host. PMID:25003382

Trichomonas vaginalis and Human Immunodeficiency Virus Coinfection Among Women Under Community Supervision: A Call for Expanded T. vaginalis Screening.

PubMed

Davis, Alissa; Dasgupta, Anindita; Goddard-Eckrich, Dawn; El-Bassel, Nabila

2016-10-01

The United States has a large community supervision population, a growing number of whom are women. Trichomonas vaginalis infection is strongly associated with an increased risk of human immunodeficiency virus (HIV) acquisition and transmission, particularly among women, but there is a paucity of research on HIV and T. vaginalis co-infection among women under community supervision. This article examines the prevalence of T. vaginalis infection and T. vaginalis and HIV coinfection at baseline among women under community supervision in New York City. It also examines the 12-month outcomes of women treated for T. vaginalis. Women received biological tests for HIV and T. vaginalis at baseline and 12 months follow-up. Of the 333 women tested for sexually transmitted infections, 77 women (23.1%) tested positive for T. vaginalis at baseline and 44 (13.3%) were HIV positive. Human immunodeficiency virus-positive women had significantly higher rates of T. vaginalis infection than HIV-negative women (36.4% vs 21.3%, P ≤ 0.05). Sixteen women (4.8%) were coinfected with T. vaginalis and HIV. Of the 77 women who were positive for T. vaginalis infection at baseline, 58 (75.3%) received treatment by a health care provider. Of those who received treatment, 17 (29.3%) tested positive for T. vaginalis at the 12-month follow-up. Given the high prevalence of T. vaginalis among this sample of women, particularly among HIV-positive women, and high levels of reinfection or persistent infection, screening for T. vaginalis among women under community supervision may have a substantial impact on reducing HIV acquisition and transmission among this high-risk population.

Cell transformation mediated by chromosomal deoxyribonucleic acid of polyoma virus-transformed cells.

PubMed Central

Della Valle, G; Fenton, R G; Basilico, C

1981-01-01

To study the mechanism of deoxyribonucleic acid (DNA)-mediated gene transfer, normal rat cells were transfected with total cellular DNA extracted from polyoma virus-transformed cells. This resulted in the appearance of the transformed phenotype in 1 X 10(-6) to 3 X 10(-6) of the transfected cells. Transformation was invariably associated with the acquisition of integrated viral DNA sequences characteristic of the donor DNA. This was caused not by the integration of free DNA molecules, but by the transfer of large DNA fragments (10 to 20 kilobases) containing linked cellular and viral sequences. Although Southern blot analysis showed that integration did not appear to occur in a homologous region of the recipient chromosome, the frequency of transformation was rather high when compared with that of purified polyoma DNA, perhaps due to "position" effects or to the high efficiency of recombination of large DNA fragments. Images PMID:6100965

Adaptation to Human Populations Is Revealed by Within-Host Polymorphisms in HIV-1 and Hepatitis C Virus

PubMed Central

Poon, Art F. Y; Kosakovsky Pond, Sergei L.; Bennett, Phil; Richman, Douglas D; Leigh Brown, Andrew J.; Frost, Simon D. W

2007-01-01

CD8+ cytotoxic T-lymphocytes (CTLs) perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately “toggle” in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1– (n ≥ 3,000) and HCV-infected patients (n ≥ 2,600) by screening bulk RT-PCR sequences for sequencing “mixtures” (i.e., ambiguous nucleotides), which act as site-specific markers of genetic variation within each host. We find that nonsynonymous mixtures are abundant and significantly associated with codon positions under host-specific CTL selection, which should deplete within-host variation by driving the fixation of the favored variant. Using a simple model, we demonstrate that this apparently contradictory outcome can be explained by the transmission of unfavorable variants to new hosts before they are removed by selection, which occurs more frequently when selection and transmission occur on similar time scales. Consequently, the circulating virus population is shaped by the transmission rate and the disparity in selection intensities for escape or reversion as much as it is shaped by the immune diversity of the host population, with potentially serious implications for vaccine design. PMID:17397261

Sero-prevalence and factors associated with Hepatitis B and C co-infection in pregnant Nigerian women living with HIV Infection

PubMed Central

Ezechi, Oliver Chukwujekwu; Kalejaiye, Olufunto Olufela; Gab-Okafor, Chidinma Vivian; Oladele, David Ayola; Oke, Bamidele Oludare; Musa, Zaidat Adesola; Ekama, Sabdat Ozichu; Ohwodo, Harry; Agahowa, Endurance; Gbajabiamilla, Titilola; Ezeobi, Paschal Mbanefo; Okwuraiwe, Azuka; Audu R, Rosemary Ajuma; Okoye, Rosemary Nwakaego; David, Agatha Nkiru; Odunukwe, Nkiruka Nonyelum; Onwujekwe, Dan Ifeanyi; Ujah, Innocent Achanya

2014-01-01

Introduction Perinatal and horizontal transmission of Hepatitis B occur in areas of high endemicity as most infections are acquired in the first 5 years of life. Unless Hepatitis B and C infected pregnant women identified, and appropriate treatment provided, children born to these women are at high risk of chronic Hepatitis B (and C) virus infection. The objecive of this study was to determined the prevalence and the factors associated with Hepatitis B and C Virus infection in pregnant HIV positive Nigerians. Methods A cross sectional study among HIV Positive pregnant women seen at a large PMTCT clinic in Lagos Nigeria. The women were screened for Hepatitis B and C Virus infection at enrollment. HIV viral load, CD4 count, liver transaminases and hemoglobin levels were also determined. Data were managed with SPSS for windows version. Ethical approval was obtained from the Institutions Ethical Review Board. Results Of the 2391 studied subjects, 101(4.2%) and 37(1.5%) respectively were seropositive for Hepatitis B and C Virus infection. Twowomen (0. 08%) had triple infections. blood transfusion, (cOR: 2.3; 95% CI:1.1 - 4.6), history of induced abortion (cOR:2. 2;95% CI:1.3 - 3.6), and elevated baseline ALT (cOR:2. 2; 95%CI:2. 2;4.2) were significantly associated with HBV. History of induced abortion was the only factor found to be associated with HIV/ HCV (cOR: 1.9;95%CI:1. 3-3.9). Conclusion Hepatitis B Virus infection (4.2%) is relatively common in our environment and associated with induced abortion, blood transfusion and elevated baseline transaminase. Hepatitis C Virus infection (1.5%) is less common and associated with only history of induced abortion. PMID:25396023

[Multiplex real-time PCR method for rapid detection of Marburg virus and Ebola virus].

PubMed

Yang, Yu; Bai, Lin; Hu, Kong-Xin; Yang, Zhi-Hong; Hu, Jian-Ping; Wang, Jing

2012-08-01

Marburg virus and Ebola virus are acute infections with high case fatality rates. A rapid, sensitive detection method was established to detect Marburg virus and Ebola virus by multiplex real-time fluorescence quantitative PCR. Designing primers and Taqman probes from highly conserved sequences of Marburg virus and Ebola virus through whole genome sequences alignment, Taqman probes labeled by FAM and Texas Red, the sensitivity of the multiplex real-time quantitative PCR assay was optimized by evaluating the different concentrations of primers and Probes. We have developed a real-time PCR method with the sensitivity of 30.5 copies/microl for Marburg virus positive plasmid and 28.6 copies/microl for Ebola virus positive plasmids, Japanese encephalitis virus, Yellow fever virus, Dengue virus were using to examine the specificity. The Multiplex real-time PCR assays provide a sensitive, reliable and efficient method to detect Marburg virus and Ebola virus simultaneously.

Usutu virus persistence and West Nile virus inactivity in the Emilia-Romagna region (Italy) in 2011.

PubMed

Calzolari, Mattia; Bonilauri, Paolo; Bellini, Romeo; Albieri, Alessandro; Defilippo, Francesco; Tamba, Marco; Tassinari, Massimo; Gelati, Antonio; Cordioli, Paolo; Angelini, Paola; Dottori, Michele

2013-01-01

The circulation of West Nile virus and Usutu virus was detected in the Emilia-Romagna region in 2008 and 2009. To evaluate the extent of circulation of both viruses, environmental surveillance, based on bird and mosquito testing, was conducted in 2008 and gradually improved over the years. In February-March 2009-2011, 5,993 hibernating mosquitoes were manually sampled, out of which 80.1% were Culex pipiens; none tested positive for the viruses. From 2008 to 2011, 946,213 mosquitoes, sampled between May and October, were tested; 86.5% were Cx. pipiens. West Nile virus was detected in 32 Cx. pipiens pools, and Usutu virus was detected in 229 mosquito pools (217 Cx. pipiens, 10 Aedes albopictus, one Anopheles maculipennis s.l., and one Aedes caspius). From 2009 to 2011, of 4,546 birds collected, 42 tested positive for West Nile virus and 48 for Usutu virus. West Nile virus and Usutu virus showed different patterns of activity during the 2008-2011 surveillance period. West Nile virus was detected in 2008, 2009, and 2010, but not in 2011. Usutu virus, however, was continuously active throughout 2009, 2010, and 2011. The data strongly suggest that both viruses overwinter in the surveyed area rather than being continually reintroduced every season. The lack of hibernating mosquitoes testing positive for the viruses and the presence of positive birds sampled early in the season support the hypothesis that the viruses overwinter in birds rather than in mosquitoes. Herd immunity in key bird species could explain the decline of West Nile virus observed in 2011, while the persistence of Usutu virus may be explained by not yet identified reservoirs. Reported results are comparable with a peri-Mediterranean circulation of the West Nile virus lineage 1 related strain, which became undetectable in the environment after two to three years of obvious circulation.

Crystallization and preliminary X-ray diffraction analysis of red clover necrotic mosaic virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, Stanton L.; Guenther, Richard H.; Sit, Tim L.

2010-11-12

Red clover necrotic mosaic virus (RCNMV) is a species that belongs to the Tombusviridae family of plant viruses with a T = 3 icosahedral capsid. RCNMV virions were purified and were crystallized for X-ray analysis using the hanging-drop vapor-diffusion method. Self-rotation functions and systematic absences identified the space group as I23, with two virions in the unit cell. The crystals diffracted to better than 4 {angstrom} resolution but were very radiation-sensitive, causing rapid decay of the high-resolution reflections. The data were processed to 6 {angstrom} in the analysis presented here.

Lack of evidence for the presence of emerging HoBi-like viruses in North American fetal bovine serum lots.

PubMed

Bauermann, Fernando V; Flores, Eduardo F; Falkenberg, Shollie M; Weiblen, Rudi; Ridpath, Julia F

2014-01-01

The detection of an emerging pestivirus species, "HoBi-like virus," in fetal bovine serum (FBS) labeled as U.S. origin, but packaged in Europe, raised concerns that HoBi-like virus may have entered the United States. In the current study, 90 lots of FBS originating in North America (NA) were screened for pestivirus antigen and antibodies. Lots in group 1 (G1, 72 samples) and group 2 (G2, 9 samples) originated in NA and were packaged in the United States. Group 3 (G3) was composed of 9 lots collected in NA and processed in Europe. Lots in G1 were claimed negative for Bovine viral diarrhea virus (BVDV), while lots in G2 and G3 were claimed positive by the commercial processor. All lots in G1 and G2 tested negative by reverse transcription polymerase chain reaction (RT-PCR) using HoBi-like-specific primers. Two G1 lots tested positive by BVDV RT-PCR. One of these was also positive by virus isolation. All G2 lots were positive by BVDV RT-PCR. In addition, four G2 lots were VI positive while 1 lot was antigen-capture enzyme-linked immunosorbent assay (ELISA) positive. Two G3 lots were positive by HoBi-like-specific RT-PCR tests. All lots were negative for HoBi_D32/00 neutralizing antibodies. Seven lots (4 G1; 1 G2; 2 G3) had antibodies against BVDV by virus neutralization and/or antigen-capture ELISA. While there is no evidence of HoBi-like viruses in NA based on tested samples, further studies are required to validate HoBi-like virus-free status and develop means to prevent the spread of HoBi-like virus into NA.

Wuhan large pig roundworm virus identified in human feces in Brazil.

PubMed

Luchs, Adriana; Leal, Elcio; Komninakis, Shirley Vasconcelos; de Pádua Milagres, Flavio Augusto; Brustulin, Rafael; da Aparecida Rodrigues Teles, Maria; Gill, Danielle Elise; Deng, Xutao; Delwart, Eric; Sabino, Ester Cerdeira; da Costa, Antonio Charlys

2018-03-28

We report here the complete genome sequence of a bipartite virus, herein denoted WLPRV/human/BRA/TO-34/201, from a sample collected in 2015 from a two-year-old child in Brazil presenting acute gastroenteritis. The virus has 98-99% identity (segments 2 and 1, respectively) with the Wuhan large pig roundworm virus (unclassified RNA virus) that was recently discovered in the stomachs of pigs from China. This is the first report of a Wuhan large pig roundworm virus detected in human specimens, and the second genome described worldwide. However, the generation of more sequence data and further functional studies are required to fully understand the ecology, epidemiology, and evolution of this new unclassified virus.

Protein Crystallization.

PubMed

McPherson, Alexander

2017-01-01

Protein crystallization was discovered by chance nearly 200 years ago and was developed in the late nineteenth century as a powerful purification tool, and a demonstration of chemical purity. The crystallization of proteins, nucleic acids, and large biological complexes, such as viruses, depends on the creation of a solution that is supersaturated in the macromolecule, but exhibits conditions that do not significantly perturb its natural state. Supersaturation is produced through the addition of mild precipitating agents such as neutral salts or polymers, and by manipulation of various parameters that include temperature, ionic strength, and pH. Also important in the crystallization process are factors that can affect the structural state of the macromolecule, such as metal ions, inhibitors, cofactors, or other conventional small molecules. A variety of approaches have been developed that combine the spectrum of factors that effect and promote crystallization, and among the most widely used are vapor diffusion, dialysis, batch, and liquid-liquid diffusion. Successes in macromolecular crystallization have multiplied rapidly in recent years due to the advent of practical, easy-to-use screening kits, and the application of laboratory robotics.

Defining the Interaction of HIV-1 with the Mucosal Barriers of the Female Reproductive Tract

PubMed Central

Carias, Ann M.; McCoombe, Scott; McRaven, Michael; Anderson, Meegan; Galloway, Nicole; Vandergrift, Nathan; Fought, Angela J.; Lurain, John; Duplantis, Maurice; Veazey, Ronald S.

2013-01-01

Worldwide, HIV-1 infects millions of people annually, the majority of whom are women. To establish infection in the female reproductive tract (FRT), HIV-1 in male ejaculate must overcome numerous innate and adaptive immune factors, traverse the genital epithelium, and establish infection in underlying CD4+ target cells. How the virus achieves this remains poorly defined. By utilizing a new technique, we define how HIV-1 interacts with different tissues of the FRT using human cervical explants and in vivo exposure in the rhesus macaque vaginal transmission model. Despite previous claims of the squamous epithelium being an efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact columnar and squamous epithelial barriers to depths where the virus can encounter potential target cells. In the squamous epithelium, we identify virus entry occurring through diffusive percolation, penetrating areas where cell junctions are absent. In the columnar epithelium, we illustrate that virus does not transverse barriers as well as previously thought due to mucus impediment. We also show a statistically significant correlation between the viral load of inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our results suggest a diffusive percolation mechanism for the initial events of HIV-1 entry. With these data, we also mathematically extrapolate the number of HIV-1 particles that penetrate the mucosa per coital act, providing a biological description of the mechanism for HIV-1 transmission during the acute and chronic stages of infection. PMID:23966398

Cell-free transmission of human adenovirus by passive mass transfer in cell culture simulated in a computer model.

PubMed

Yakimovich, Artur; Gumpert, Heidi; Burckhardt, Christoph J; Lütschg, Verena A; Jurgeit, Andreas; Sbalzarini, Ivo F; Greber, Urs F

2012-09-01

Viruses spread between cells, tissues, and organisms by cell-free and cell-cell transmissions. Both mechanisms enhance disease development, but it is difficult to distinguish between them. Here, we analyzed the transmission mode of human adenovirus (HAdV) in monolayers of epithelial cells by wet laboratory experimentation and a computer simulation. Using live-cell fluorescence microscopy and replication-competent HAdV2 expressing green fluorescent protein, we found that the spread of infection invariably occurred after cell lysis. It was affected by convection and blocked by neutralizing antibodies but was independent of second-round infections. If cells were overlaid with agarose, convection was blocked and round plaques developed around lytic infected cells. Infected cells that did not lyse did not give rise to plaques, highlighting the importance of cell-free transmission. Key parameters for cell-free virus transmission were the time from infection to lysis, the dose of free viruses determining infection probability, and the diffusion of single HAdV particles in aqueous medium. With these parameters, we developed an in silico model using multiscale hybrid dynamics, cellular automata, and particle strength exchange. This so-called white box model is based on experimentally determined parameters and reproduces viral infection spreading as a function of the local concentration of free viruses. These analyses imply that the extent of lytic infections can be determined by either direct plaque assays or can be predicted by calculations of virus diffusion constants and modeling.

The role of human papilloma virus and herpes viruses in the etiology of nasal polyposis.

PubMed

Koçoğlu, Mücahide Esra; Mengeloğlu, Fırat Zafer; Apuhan, Tayfun; Özsoy, Şeyda; Yilmaz, Beyhan

2016-02-17

The aim of this study was to investigate the etiological role of human papilloma virus (HPV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6) and -7 (HHV-7) in the occurrence of nasal polyposis. Nasal polyp samples from 30 patients with nasal polyposis and normal nasal mucosa from 10 patients without nasal polyps were obtained. DNA was extracted from tissues. Real-time polymerase chain reaction was performed for all runs. No HSV-1, HSV-2, or VZV was detected in the samples. Among the patient samples, EBV and HHV-7 DNA were detected in 18 (60%), HHV-6 was detected in 20 (66.7%), and HPV was detected in 4 (13.3%) samples. Among the controls, CMV DNA was positive in one (10%). EBV was positive in 5 (50%), HHV-6 and HHV-7 were positive in 7 (70%), and HPV was positive in 2 (20%) samples. No significant difference was found among the groups with any test in terms of positivity. The association of Herpesviridae and HPV with the pathogenesis of nasal polyps was investigated in this study and no relationship was found. Thus, these viruses do not play a significant role in the formation of nasal polyps.

Investigating plasmodesmata genetics with virus-induced gene silencing and an agrobacterium-mediated GFP movement assay.

PubMed

Brunkard, Jacob O; Burch-Smith, Tessa M; Runkel, Anne M; Zambryski, Patricia

2015-01-01

Plasmodesmata (PD) are channels that connect the cytoplasm of adjacent plant cells, permitting intercellular transport and communication. PD function and formation are essential to plant growth and development, but we still know very little about the genetic pathways regulating PD transport. Here, we present a method for assaying changes in the rate of PD transport following genetic manipulation. Gene expression in leaves is modified by virus-induced gene silencing. Seven to ten days after infection with Tobacco rattle virus carrying a silencing trigger, the gene(s) of interest is silenced in newly arising leaves. In these new leaves, individual cells are then transformed with Agrobacterium to express GFP, and the rate of GFP diffusion via PD is measured. By measuring GFP diffusion both within the epidermis and between the epidermis and mesophyll, the assay can be used to study the effects of silencing a gene(s) on PD transport in general, or transport through secondary PD specifically. Plant biologists working in several fields will find this assay useful, since PD transport impacts plant physiology, development, and defense.

Spreading and vanishing in a West Nile virus model with expanding fronts

NASA Astrophysics Data System (ADS)

Tarboush, Abdelrazig K.; Lin, ZhiGui; Zhang, MengYun

2017-05-01

In this paper, we study a simplified version of a West Nile virus model discussed by Lewis et al. [28], which was considered as a first approximation for the spatial spread of WNv. The basic reproduction number $R_0$ for the non-spatial epidemic model is defined and a threshold parameter $R_0 ^D$ for the corresponding problem with null Dirichlet boundary condition is introduced. We consider a free boundary problem with coupled system, which describes the diffusion of birds by a PDE and the movement of mosquitoes by a ODE. The risk index $R_0^F (t)$ associated with the disease in spatial setting is represented. Sufficient conditions for the WNv to eradicate or to spread are given. The asymptotic behavior of the solution to system when the spreading occurs are considered. It is shown that the initial number of infected populations, the diffusion rate of birds and the length of initial habitat exhibit important impacts on the vanishing or spreading of the virus. Numerical simulations are presented to illustrate the analytical results.

Burden and Seasonality of Viral Acute Respiratory Tract Infections among Outpatients in Southern Sri Lanka.

PubMed

Shapiro, David; Bodinayake, Champica K; Nagahawatte, Ajith; Devasiri, Vasantha; Kurukulasooriya, Ruvini; Hsiang, Jeremy; Nicholson, Bradley; De Silva, Aruna Dharshan; Østbye, Truls; Reller, Megan E; Woods, Christopher W; Tillekeratne, L Gayani

2017-07-01

In tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. We determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern Sri Lanka. From March 2013 to January 2015, we enrolled outpatients presenting with influenza-like illness (ILI). Nasal/nasopharyngeal samples were tested in duplicate using antigen-based rapid influenza testing and multiplex polymerase chain reaction (PCR) for respiratory viruses. Monthly proportion positive was calculated for each virus. Bivariable and multivariable logistic regression were used to identify associations between sociodemographic/clinical information and viral detection. Of 571 subjects, most (470, 82.3%) were ≥ 5 years of age and 53.1% were male. A respiratory virus was detected by PCR in 63.6% ( N = 363). Common viral etiologies included influenza (223, 39%), human enterovirus/rhinovirus (HEV/HRV, 14.5%), respiratory syncytial virus (RSV, 4.2%), and human metapneumovirus (hMPV, 3.9%). Both ILI and influenza showed clear seasonal variation, with peaks from March to June each year. RSV and hMPV activity peaked from May to July, whereas HEV/HRV was seen year-round. Patients with respiratory viruses detected were more likely to report pain with breathing (odds ratio [OR] = 2.60, P = 0.003), anorexia (OR = 2.29, P < 0.001), and fatigue (OR = 2.00, P = 0.002) compared with patients with no respiratory viruses detected. ILI showed clear seasonal variation in southern Sri Lanka, with most activity during March to June; peak activity was largely due to influenza. Targeted infection prevention activities such as influenza vaccination in January-February may have a large public health impact in this region.

Copanlisib and Nivolumab in Treating Participants With Recurrent or Refractory Diffuse Large B-cell Lymphoma or Primary Mediastinal Large B-cell Lymphoma

ClinicalTrials.gov

2018-06-11

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma

Whole-proteome phylogeny of large dsDNA viruses and parvoviruses through a composition vector method related to dynamical language model

PubMed Central

2010-01-01

Background The vast sequence divergence among different virus groups has presented a great challenge to alignment-based analysis of virus phylogeny. Due to the problems caused by the uncertainty in alignment, existing tools for phylogenetic analysis based on multiple alignment could not be directly applied to the whole-genome comparison and phylogenomic studies of viruses. There has been a growing interest in alignment-free methods for phylogenetic analysis using complete genome data. Among the alignment-free methods, a dynamical language (DL) method proposed by our group has successfully been applied to the phylogenetic analysis of bacteria and chloroplast genomes. Results In this paper, the DL method is used to analyze the whole-proteome phylogeny of 124 large dsDNA viruses and 30 parvoviruses, two data sets with large difference in genome size. The trees from our analyses are in good agreement to the latest classification of large dsDNA viruses and parvoviruses by the International Committee on Taxonomy of Viruses (ICTV). Conclusions The present method provides a new way for recovering the phylogeny of large dsDNA viruses and parvoviruses, and also some insights on the affiliation of a number of unclassified viruses. In comparison, some alignment-free methods such as the CV Tree method can be used for recovering the phylogeny of large dsDNA viruses, but they are not suitable for resolving the phylogeny of parvoviruses with a much smaller genome size. PMID:20565983

Immunohistochemical detection of autophagy-related microtubule-associated protein 1 light chain 3 (LC3) in the cerebellums of dogs naturally infected with canine distemper virus.

PubMed

Kabak, Y B; Sozmen, M; Yarim, M; Guvenc, T; Karayigit, M O; Gulbahar, M Y

2015-01-01

We investigated the expression of microtubule-associated protein 1 light chain 3 (LC3) protein in the cerebellums of dogs infected with canine distemper virus (CDV) using immunohistochemistry to detect autophagy. The cerebellums of 20 dogs infected with CDV were used. Specimens showing demyelination of white matter were considered to have an acute infection, whereas specimens showing signs of severe perivascular cuffing and demyelination of white matter were classified as having chronic CDV. Cerebellar sections were immunostained with CDV and LC3 antibodies. The cytoplasm of Purkinje cells, granular layer cells, motor neurons in large cerebellar ganglia and some neurons in white matter were positive for the LC3 antibody in both the control and CDV-infected dogs. In the infected cerebellums, however, white matter was immunostained more intensely, particularly the neurons and gemistocytic astrocytes in the demyelinated areas, compared to controls. Autophagy also was demonstrated in CDV-positive cells using double immunofluorescence staining. Our findings indicate that increased autophagy in the cerebellum of dogs naturally infected with CDV may play a role in transferring the virus from cell to cell.

Wind-Mediated Spread of Low-Pathogenic Avian Influenza Virus into the Environment during Outbreaks at Commercial Poultry Farms.

PubMed

Jonges, Marcel; van Leuken, Jeroen; Wouters, Inge; Koch, Guus; Meijer, Adam; Koopmans, Marion

2015-01-01

Avian influenza virus-infected poultry can release a large amount of virus-contaminated droppings that serve as sources of infection for susceptible birds. Much research so far has focused on virus spread within flocks. However, as fecal material or manure is a major constituent of airborne poultry dust, virus-contaminated particulate matter from infected flocks may be dispersed into the environment. We collected samples of suspended particulate matter, or the inhalable dust fraction, inside, upwind and downwind of buildings holding poultry infected with low-pathogenic avian influenza virus, and tested them for the presence of endotoxins and influenza virus to characterize the potential impact of airborne influenza virus transmission during outbreaks at commercial poultry farms. Influenza viruses were detected by RT-PCR in filter-rinse fluids collected up to 60 meters downwind from the barns, but virus isolation did not yield any isolates. Viral loads in the air samples were low and beyond the limit of RT-PCR quantification except for one in-barn measurement showing a virus concentration of 8.48 x 10(4) genome copies/m(3). Air samples taken outside poultry barns had endotoxin concentrations of ~50 EU/m(3) that declined with increasing distance from the barn. Atmospheric dispersion modeling of particulate matter, using location-specific meteorological data for the sampling days, demonstrated a positive correlation between endotoxin measurements and modeled particulate matter concentrations, with an R(2) varying from 0.59 to 0.88. Our data suggest that areas at high risk for human or animal exposure to airborne influenza viruses can be modeled during an outbreak to allow directed interventions following targeted surveillance.

Varroa destructor Macula-like virus, Lake Sinai virus and other new RNA viruses in wild bumblebee hosts (Bombus pascuorum, Bombus lapidarius and Bombus pratorum).

PubMed

Parmentier, Laurian; Smagghe, Guy; de Graaf, Dirk C; Meeus, Ivan

2016-02-01

Pollinators such as bumblebees (Bombus spp.) are in decline worldwide which poses a threat not only for ecosystem biodiversity but also to human crop production services. One main cause of pollinator decline may be the infection and transmission of diseases including RNA viruses. Recently, new viruses have been discovered in honeybees, but information on the presence of these in wild bumblebees is largely not available. In this study, we investigated the prevalence of new RNA viruses in Bombus species, and can report for the first time Varroa destructor Macula-like virus (VdMLV) and Lake Sinai virus (LSV) infection in multiple wild bumblebee hosts of Bombus pascuorum, Bombus lapidarius and Bombus pratorum. We sampled in 4 locations in Flanders, Belgium. Besides, we confirmed Slow bee paralysis virus (SBPV) in wild bumblebees, but no positive samples were obtained for Big Sioux river virus (BSRV). Secondly, we screened for the influence of apiaries on the prevalence of these viruses. Our results indicated a location effect for the prevalence of VdMLV in Bombus species, with a higher prevalence in the proximity of honeybee apiaries mainly observed in one location. For LSV, the prevalence was not different in the proximity or at a 1.5 km-distance of apiaries, but we reported a different isolate with similarities to LSV-2 and "LSV-clade A" as described by Ravoet et al. (2015), which was detected both in Apis mellifera and Bombus species. In general, our results indicate the existence of a disease pool of new viruses that seems to be associated to a broad range of Apoidae hosts, including multiple Bombus species. Copyright © 2015 Elsevier Inc. All rights reserved.

The development and psychometric analysis of the Chinese HIV-Related Fatigue Scale.

PubMed

Li, Su-Yin; Wu, Hua-Shan; Barroso, Julie

2016-04-01

To develop a Chinese version of the human immunodeficiency virus-related Fatigue Scale and examine its reliability and validity. Fatigue is found in more than 70% of people infected with human immunodeficiency virus. However, a scale to assess fatigue in human immunodeficiency virus-positive people has not yet been developed for use in Chinese-speaking countries. A methodologic study involving instrument development and psychometric evaluation was used. The human immunodeficiency virus-related Fatigue Scale was examined through a two-step procedure: (1) translation and back translation and (2) psychometric analysis. A sample of 142 human immunodeficiency virus-positive patients was recruited from the Infectious Disease Outpatient Clinic in central Taiwan. Their fatigue data were analysed with Cronbach's α for internal consistency. Two weeks later, the data of a random sample of 28 patients from the original 142 were analysed for test-retest reliability. The correlation between the World Health Organization Quality of Life Assessment-Human Immunodeficiency Virus and the Chinese version of the human immunodeficiency virus-related Fatigue Scale was analysed for concurrent validity. The Chinese version of the human immunodeficiency virus-related Fatigue Scale scores of human immunodeficiency virus-positive patients with highly active antiretroviral therapy and those without were compared to demonstrate construct validity. The internal consistency and test-retest reliability of the Chinese version of the human immunodeficiency virus-related Fatigue Scale were 0·97 and 0·686, respectively. In regard to concurrent validity, a negative correlation was found between the scores of the Chinese version of the human immunodeficiency virus-related Fatigue Scale and the World Health Organization Quality of Life Assessment-Human Immunodeficiency Virus. Additionally, the Chinese version of the human immunodeficiency virus-related Fatigue Scale could be used to effectively distinguish fatigue differences between the human immunodeficiency virus-positive patients with highly active antiretroviral therapy and those without. The Chinese version of the human immunodeficiency virus-related Fatigue Scale presents good reliability and validity through a robust psychometric analysis. This scale can be appropriately applied to human immunodeficiency virus-positive patients by clinical staff and case managers in Chinese-speaking countries. The Chinese version of the human immunodeficiency virus-related Fatigue Scale is an effective and comprehensive tool that can help clinical professionals measure the frequency, strength and impact on the quality of life of fatigue in Chinese human immunodeficiency virus-positive patients. © 2016 John Wiley & Sons Ltd.

Patterns of feline immunodeficiency virus multiple infection and genome divergence in a free-ranging population of African lions.

PubMed

Troyer, Jennifer L; Pecon-Slattery, Jill; Roelke, Melody E; Black, Lori; Packer, Craig; O'Brien, Stephen J

2004-04-01

Feline immunodeficiency virus (FIV) is a lentivirus that causes AIDS-like immunodeficiency disease in domestic cats. Free-ranging lions, Panthera leo, carry a chronic species-specific strain of FIV, FIV-Ple, which so far has not been convincingly connected with immune pathology or mortality. FIV-Ple, harboring the three distinct strains A, B, and C defined by pol gene sequence divergences, is endemic in the large outbred population of lions in the Serengeti ecosystem in Tanzania. Here we describe the pattern of variation in the three FIV genes gag, pol-RT, and pol-RNase among lions within 13 prides to assess the occurrence of FIV infection and coinfection. Genome diversity within and among FIV-Ple strains is shown to be large, with strain divergence for each gene approaching genetic distances observed for FIV between different species of cats. Multiple in fections with two or three strains were found in 43% of the FIV-positive individuals based on pol-RT sequence analysis, which may suggest that antiviral immunity or interference evoked by one strain is not consistently protective against infection by a second. This comprehensive study of FIV-Ple in a free-ranging population of lions reveals a dynamic transmission of virus in a social species that has historically adapted to render the virus benign.

Patterns of Feline Immunodeficiency Virus Multiple Infection and Genome Divergence in a Free-Ranging Population of African Lions

PubMed Central

Troyer, Jennifer L.; Pecon-Slattery, Jill; Roelke, Melody E.; Black, Lori; Packer, Craig; O'Brien, Stephen J.

2004-01-01

Feline immunodeficiency virus (FIV) is a lentivirus that causes AIDS-like immunodeficiency disease in domestic cats. Free-ranging lions, Panthera leo, carry a chronic species-specific strain of FIV, FIV-Ple, which so far has not been convincingly connected with immune pathology or mortality. FIV-Ple, harboring the three distinct strains A, B, and C defined by pol gene sequence divergences, is endemic in the large outbred population of lions in the Serengeti ecosystem in Tanzania. Here we describe the pattern of variation in the three FIV genes gag, pol-RT, and pol-RNase among lions within 13 prides to assess the occurrence of FIV infection and coinfection. Genome diversity within and among FIV-Ple strains is shown to be large, with strain divergence for each gene approaching genetic distances observed for FIV between different species of cats. Multiple in fections with two or three strains were found in 43% of the FIV-positive individuals based on pol-RT sequence analysis, which may suggest that antiviral immunity or interference evoked by one strain is not consistently protective against infection by a second. This comprehensive study of FIV-Ple in a free-ranging population of lions reveals a dynamic transmission of virus in a social species that has historically adapted to render the virus benign. PMID:15016897

Women's awareness of the human papilloma virus and related health problems.

PubMed

Akyuz, Aygul; Yılmaz, Cevriye; Yenen, Müfit Cemal; Yavan, Tülay; Kılıç, Ayşe

2011-12-01

This paper is a report of a study of women's awareness of the human papilloma virus and related health problems. Cervical cancer is an important cause of mortality, making up approximately 12% of all cancers in women. Awareness on the part of carriers of human papilloma virus is crucial in preventing transmission of the infection and protecting against cervical cancer. The study was performed as a cross-sectional descriptive study. The study consists of 79 human papilloma virus-positive women who had not been diagnosed with cervical cancer and 150 women who had not been diagnosed with human papilloma virus. Data were collected via questionnaires between November 2007 and April 2008. Percentages and chi-square test were used. A significantly higher percentage of women with positive human papilloma virus knew the definition of human papilloma virus, the fact that it is transmitted via sexual contact and that it can lead to cervical cancer than did women with negative human papilloma virus. It was established that approximately half the women with positive human papilloma virus presented at the hospital with a genital wart. None of the women knew that a Pap smear test was a necessary tool in the prevention of cervical cancer. Women with positive human papilloma virus have insufficient knowledge of human papilloma virus, sexually transmitted diseases, the health risks associated with human papilloma virus and the means of preventing these risks. It is therefore necessary to evaluate the education of health workers, and especially of nurses, on human papilloma virus and its prevention. © 2011 Blackwell Publishing Ltd.

Mechanisms of lithium transport in amorphous polyethylene oxide.

PubMed

Duan, Yuhua; Halley, J W; Curtiss, Larry; Redfern, Paul

2005-02-01

We report calculations using a previously reported model of lithium perchlorate in polyethylene oxide in order to understand the mechanism of lithium transport in these systems. Using an algorithm suggested by Voter, we find results for the diffusion rate which are quite close to experimental values. By analysis of the individual events in which large lithium motions occur during short times, we find that no single type of rearrangement of the lithium environment characterizes these events. We estimate the free energies of the lithium ion as a function of position during these events by calculation of potentials of mean force and thus derive an approximate map of the free energy as a function of lithium position during these events. The results are consistent with a Marcus-like picture in which the system slowly climbs a free energy barrier dominated by rearrangement of the polymer around the lithium ions, after which the lithium moves very quickly to a new position. Reducing the torsion forces in the model causes the diffusion rates to increase.

Experimentally guided models reveal replication principles that shape the mutation distribution of RNA viruses

PubMed Central

Schulte, Michael B; Draghi, Jeremy A; Plotkin, Joshua B; Andino, Raul

2015-01-01

Life history theory posits that the sequence and timing of events in an organism's lifespan are fine-tuned by evolution to maximize the production of viable offspring. In a virus, a life history strategy is largely manifested in its replication mode. Here, we develop a stochastic mathematical model to infer the replication mode shaping the structure and mutation distribution of a poliovirus population in an intact single infected cell. We measure production of RNA and poliovirus particles through the infection cycle, and use these data to infer the parameters of our model. We find that on average the viral progeny produced from each cell are approximately five generations removed from the infecting virus. Multiple generations within a single cell infection provide opportunities for significant accumulation of mutations per viral genome and for intracellular selection. DOI: http://dx.doi.org/10.7554/eLife.03753.001 PMID:25635405

Evaluation of sewage source and fate on southeast Florida coastal reefs

USGS Publications Warehouse

Carrie, Futch J.; Griffin, Dale W.; Banks, K.; Lipp, E.K.

2011-01-01

Water, sponge and coral samples were collected from stations impacted by a variety of pollution sources and screened for human enteric viruses as conservative markers for human sewage. While human enteroviruses and adenoviruses were not detected, noroviruses (NoV; human genogroups I and II) were detected in 31% of samples (especially in sponge tissue). Stations near inlets were the only ones to show multiple sample types positive for NoV. Fecal indicator bacteria and enteric viruses were further evaluated at multiple inlet stations on an outgoing tide. Greatest indicator concentrations and highest prevalence of viruses were found at the mouth of the inlet and offshore in the inlet plume. Results suggest that inlets moving large volumes of water into the coastal zone with tides may be an important source of fecal contaminants. Efforts to reduce run-off or unintended release of water into the Intracoastal Waterway may lower contaminants entering sensitive coastal areas. ?? 2011 Elsevier Ltd.

Low frequency mechanical modes of viruses with atomic detail

NASA Astrophysics Data System (ADS)

Dykeman, Eric; Sankey, Otto

2008-03-01

The low frequency mechanical modes of viruses can provide important insights into the large global motions that a virus may exhibit. Recently it has been proposed that these large global motions may be excited using impulsive stimulated Raman scattering producing permanent damage to the virus. In order to understand the coupling of external probes to the capsid, vibrational modes with atomic detail are essential. The standard approach to find the atomic modes of a molecule with N atoms requires the formation and diagonlization of a 3Nx3N matrix. As viruses have 10^5 or more atoms, the standard approach is difficult. Using ideas from electronic structure theory, we have developed a method to construct the mechanical modes of large molecules such as viruses with atomic detail. Application to viruses such as the cowpea chlorotic mottle virus, satellite tobacco necrosis virus, and M13 bacteriophage show a fairly complicated picture of the mechanical modes.

Sub-diffusion and trapped dynamics of neutral and charged probes in DNA-protein coacervates

NASA Astrophysics Data System (ADS)

Arfin, Najmul; Yadav, Avinash Chand; Bohidar, H. B.

2013-11-01

The physical mechanism leading to the formation of large intermolecular DNA-protein complexes has been studied. Our study aims to explain the occurrence of fast coacervation dynamics at the charge neutralization point, followed by the appearance of smaller complexes and slower coacervation dynamics as the complex experiences overcharging. Furthermore, the electrostatic potential and probe mobility was investigated to mimic the transport of DNA / DNA-protein complex in a DNA-protein complex coacervate medium [N. Arfin and H. B. Bohidar, J. Phys. Chem. B 116, 13192 (2012)] by assigning neutral, negative, or positive charge to the probe particle. The mobility of the neutral probe was maximal at low matrix concentrations and showed random walk behavior, while its mobility ceased at the jamming concentration of c = 0.6, showing sub-diffusion and trapped dynamics. The positively charged probe showed sub-diffusive random walk followed by trapped dynamics, while the negatively charged probe showed trapping with occasional hopping dynamics at much lower concentrations. Sub-diffusion of the probe was observed in all cases under consideration, where the electrostatic interaction was used exclusively as the dominant force involved in the dynamics. For neutral and positive probes, the mean square displacement ⟨R2⟩ exhibits a scaling with time as ⟨R2⟩ ˜ tα, distinguishing random walk and trapped dynamics at α = 0.64 ± 0.04 at c = 0.12 and c = 0.6, respectively. In addition, the same scaling factors with the exponent β = 0.64 ± 0.04 can be used to distinguish random walk and trapped dynamics for the neutral and positive probes using the relation between the number of distinct sites visited by the probe, S(t), which follows the scaling, S(t) ˜ tβ/ln (t). Our results established the occurrence of a hierarchy of diffusion dynamics experienced by a probe in a dense medium that is either charged or neutral.

Experimental layout, data analysis, and thresholds in ELISA testing of maize for aphid-borne viruses.

PubMed

Caciagli, P; Verderio, A

2003-06-30

Several aspects of enzyme-linked immunosorbent assay (ELISA) procedures and data analysis have been examined in an attempt to find a rapid and reliable method for discriminating between 'positive' and 'negative' results when testing a large number of samples. A layout of ELISA plates was designed to reduce uncontrolled variation and to optimize the number of negative and positive controls. A transformation using the fourth root (A(1/4)) of the optical density readings corrected for the blank (A) stabilized the variance of most ELISA data examined. Transformed A values were used to calculate the true limits, at a set protection level, for false positive (C) and false negative (D). Methods are discussed to reduce the number of undifferentiated samples, i.e. the samples with response falling between C and D. The whole procedure was set up for use with an electronic spreadsheet. With the addition of few instructions of the type 'if em leader then em leader else' in the spreadsheet, the ELISA results were obtained in the simple trichotomous form 'negative/undefined/positive'. This allowed rapid analysis of more than 1100 maize samples testing for the presence of seven aphid-borne viruses-in fact almost 8000 ELISA samples.

Accumulation of MS2, GA, and Qβ phages on high density polyethylene (HDPE) and drinking water biofilms under flow/non-flow conditions.

PubMed

Pelleïeux, Sandra; Bertrand, Isabelle; Skali-Lami, Salaheddine; Mathieu, Laurence; Francius, Grégory; Gantzer, Christophe

2012-12-01

Accumulation of enteric viruses on surfaces within a drinking water distribution system was investigated in a reactor using three F-specific RNA bacteriophages (MS2, GA, and Qβ) as models of human pathogenic viruses. The influence of hydrodynamic versus hydrostatic conditions and the effect of the colonization of HDPE surfaces with two-month-old biofilms were assessed for virus accumulation on surfaces. In order to work under controlled laminar conditions and to study various wall shear stresses at the same time, a new rotating disc reactor was designed. Among the wall shear rates applied in the reactor (450 to 1640 s(-1)) no significant differences were observed concerning both the total number of bacteria, which was found to be around 1.7 × 10(7) cells/cm(2) and the virus concentrations on surfaces were about 3 × 10(4), 5 × 10(5) and 3 × 10(5) eq PFU/cm(2) for MS2, GA and Qβ phages, respectively. Comparison between static versus dynamic conditions revealed that both Brownian diffusion and convective diffusion were involved in the transport of these soft colloidal particles and an increase reaching about 1 log in virus concentrations measured on surfaces appeared when hydrodynamic conditions where applied. Our results also showed the influence of the colonization by two-month-old drinking water biofilms which led to a change in the level of virus adhesion. The implication of the physico-chemical properties was also underlined since different adhesion profiles were obtained for the three bacteriophages and MS2 phage was found to be the less adherent one whatever the conditions applied. Copyright © 2012 Elsevier Ltd. All rights reserved.

Diffuse Large Cell Lymphoma Presenting as a Sacral Mass and Lupus Anticoagulant

PubMed Central

Ediriwickrema, Lilangi S.; Zaheer, Wajih

2011-01-01

A 67-year-old gentleman presented to Yale-New Haven Hospital (YNHH) for assessment of a supratherapeutic INR and sacral lesion. Hematologic workup revealed elevated ESR, PT, INR, PTT, and CRP, mixing studies that failed to correct, and a positive Russell Viper Venom Test (RVVT), which confirmed the presence of lupus anticoagulant (LA), a subtype of antiphospholipid syndrome (APA). Pathology of the patient’s sacral lesion revealed diffuse large B-cell lymphoma. This case provides insight into the association between APA and lymphoid neoplasm. The patient’s unique presentation is in marked contrast to other reports of APA and lymphoid malignancy, which are typically associated with elevated PTT, normal PT, minimal extranodal disease, and potential thrombotic complications. Further, treatment with Rituximab-CHOP chemotherapy led to excellent clinical response with tumor remission and normalization of PT and PTT. PMID:22180680

Diffuse large cell lymphoma presenting as a sacral mass and lupus anticoagulant.

PubMed

Ediriwickrema, Lilangi S; Zaheer, Wajih

2011-12-01

A 67-year-old gentleman presented to Yale-New Haven Hospital (YNHH) for assessment of a supratherapeutic INR and sacral lesion. Hematologic workup revealed elevated ESR, PT, INR, PTT, and CRP, mixing studies that failed to correct, and a positive Russell Viper Venom Test (RVVT), which confirmed the presence of lupus anticoagulant (LA), a subtype of antiphospholipid syndrome (APA). Pathology of the patient's sacral lesion revealed diffuse large B-cell lymphoma. This case provides insight into the association between APA and lymphoid neoplasm. The patient's unique presentation is in marked contrast to other reports of APA and lymphoid malignancy, which are typically associated with elevated PTT, normal PT, minimal extranodal disease, and potential thrombotic complications. Further, treatment with Rituximab-CHOP chemotherapy led to excellent clinical response with tumor remission and normalization of PT and PTT.

Parvovirus-like particles as vaccine vectors.

PubMed

Casal, J I; Rueda, P; Hurtado, A

1999-09-01

A wide array of systems have been developed to improve "classic" vaccines. The use of small polypeptides able to elicit potent antibody and cytotoxic responses seems to have enormous potential in the design of safer vaccines. While peptide coupling to large soluble proteins such as keyhole limpet hemocyanin is the current method of choice for eliciting antibody responses and insertion in live viruses for cytotoxic T-lymphocyte responses, alternative cheaper and/or safer methods will clearly be required in the future. Virus-like particles constitute very immunogenic molecules that allow for covalent coupling of the epitopes of interest in a simple way. In this article, we detail the methodology employed for the preparation of efficient virus vectors as delivery systems. We used parvovirus as the model for the design of new vaccine vectors. Recently parvovirus-like particles have been engineered to express foreign polypeptides in certain positions, resulting in the production of large quantities of highly immunogenic peptides, and to induce strong antibody, helper-T-cell, and cytotoxic T-lymphocyte responses. We discuss the different alternatives and the necessary steps to carry out this process, placing special emphasis on the flow of decisions that need to be made during the project. Copyright 1999 Academic Press.

Focal Cortical Dysplasia (FCD) lesion analysis with complex diffusion approach.

PubMed

Rajan, Jeny; Kannan, K; Kesavadas, C; Thomas, Bejoy

2009-10-01

Identification of Focal Cortical Dysplasia (FCD) can be difficult due to the subtle MRI changes. Though sequences like FLAIR (fluid attenuated inversion recovery) can detect a large majority of these lesions, there are smaller lesions without signal changes that can easily go unnoticed by the naked eye. The aim of this study is to improve the visibility of focal cortical dysplasia lesions in the T1 weighted brain MRI images. In the proposed method, we used a complex diffusion based approach for calculating the FCD affected areas. Based on the diffused image and thickness map, a complex map is created. From this complex map; FCD areas can be easily identified. MRI brains of 48 subjects selected by neuroradiologists were given to computer scientists who developed the complex map for identifying the cortical dysplasia. The scientists were blinded to the MRI interpretation result of the neuroradiologist. The FCD could be identified in all the patients in whom surgery was done, however three patients had false positive lesions. More lesions were identified in patients in whom surgery was not performed and lesions were seen in few of the controls. These were considered as false positive. This computer aided detection technique using complex diffusion approach can help detect focal cortical dysplasia in patients with epilepsy.

Three cases of mumps virus and enterovirus coinfection in children with enteroviral meningitis

PubMed Central

Rasti, Mojtaba; Makvandi, Manoochehr; Neisi, Niloofar; Azaran, Azarakhsh; Rastegarvand, Nasrin; Khalafkhany, Davod; Jahangirnezhad, Emad; Teimoori, Ali; Hadian, Maryam; Shabani, Abdolnabi; Shamsizadeh, Ahmad; Nikfar, Roya; Varnaseri, Mehran

2016-01-01

Abstract Several viruses are responsible for aseptic meningitis; however, in the region of Southwest Iran, the role played by each virus is still not very well known. The aim of this study is to determine the relative frequencies of mumps virus, herpes viruses, and enteroviruses, as well as coinfections among them, in patients with aseptic meningitis. In this cross-sectional study, samples of cerebrospinal fluid were collected between December 2012 and December 2013 from patients under 14 years, who were hospitalized in Abuzar Children's Hospital in Ahvaz, Southwest Iran (the only children's hospital in Khuzestan province and Southwest Iran). All 66 cerebrospinal fluid samples and corresponding clinical data were collected from patients with aseptic meningitis by specialists, and with the patients’ consent. The DNA and RNA were extracted from these samples and subjected to polymerase chain reaction as well as reverse transcription polymerase chain reaction (RT-PCR) for detection of mumps virus, herpes viruses, and enteroviruses. Nine of the samples (3 mumps-positive and 6 enterovirus-positive) were sequenced. The mumps virus sequences were investigated for possible mutations in the SH and partial HN regions. Up to 39 patients (59.09%) were found to be positive for enteroviruses, 3 (4.5%) for mumps virus, and 1 (1.5%) for herpes viruses (specifically, the varicella-zoster virus). Two patients (3.03%) had a mumps virus and enterovirus coinfection. Among the 3 detected mumps virus samples, 1 belonged to genotype B, while the others belonged to genotype N. Six sequenced enteroviruses indicated the highest similarity with Echovirus 30. An amino acid substitution at position 51 (N→T) was detected in the HN region of genotype N mumps virus samples, in comparison to the reference strain. PMID:27930588

Three cases of mumps virus and enterovirus coinfection in children with enteroviral meningitis.

PubMed

Rasti, Mojtaba; Makvandi, Manoochehr; Neisi, Niloofar; Azaran, Azarakhsh; Rastegarvand, Nasrin; Khalafkhany, Davod; Jahangirnezhad, Emad; Teimoori, Ali; Hadian, Maryam; Shabani, Abdolnabi; Shamsizadeh, Ahmad; Nikfar, Roya; Varnaseri, Mehran

2016-12-01

Several viruses are responsible for aseptic meningitis; however, in the region of Southwest Iran, the role played by each virus is still not very well known. The aim of this study is to determine the relative frequencies of mumps virus, herpes viruses, and enteroviruses, as well as coinfections among them, in patients with aseptic meningitis.In this cross-sectional study, samples of cerebrospinal fluid were collected between December 2012 and December 2013 from patients under 14 years, who were hospitalized in Abuzar Children's Hospital in Ahvaz, Southwest Iran (the only children's hospital in Khuzestan province and Southwest Iran).All 66 cerebrospinal fluid samples and corresponding clinical data were collected from patients with aseptic meningitis by specialists, and with the patients' consent. The DNA and RNA were extracted from these samples and subjected to polymerase chain reaction as well as reverse transcription polymerase chain reaction (RT-PCR) for detection of mumps virus, herpes viruses, and enteroviruses. Nine of the samples (3 mumps-positive and 6 enterovirus-positive) were sequenced. The mumps virus sequences were investigated for possible mutations in the SH and partial HN regions.Up to 39 patients (59.09%) were found to be positive for enteroviruses, 3 (4.5%) for mumps virus, and 1 (1.5%) for herpes viruses (specifically, the varicella-zoster virus). Two patients (3.03%) had a mumps virus and enterovirus coinfection. Among the 3 detected mumps virus samples, 1 belonged to genotype B, while the others belonged to genotype N. Six sequenced enteroviruses indicated the highest similarity with Echovirus 30. An amino acid substitution at position 51 (N→T) was detected in the HN region of genotype N mumps virus samples, in comparison to the reference strain.

Liver grafts from hepatitis B surface antigen-positive donors: A review of the literature.

PubMed

Loggi, Elisabetta; Conti, Fabio; Cucchetti, Alessandro; Ercolani, Giorgio; Pinna, Antonio Daniele; Andreone, Pietro

2016-09-21

The scarcity of available organs and the gap between supply and demand continue to be the main limitations of liver transplantation. To relieve the organ shortage, current transplant strategies have implemented extended criteria, which include the use of liver from patients with signs of past or present hepatitis B virus (HBV) infection. While the use of liver grafts from donors with evidence of past HBV infection is quite limited, some data have been collected regarding the feasibility of transplanting a liver graft from a hepatitis B surface antigen (HBsAg) positive donor. The aim of the present work was to review the literature regarding liver transplants from HBsAg-positive donors. A total of 17 studies were identified by a search in Medline. To date, HBsAg positive grafts have preferentially been allocated to HBsAg positive recipients. The large majority of these patients continue to be HBsAg positive despite the use of immunoglobulin, and infection prevention can only be guaranteed by using antiviral prophylaxis. Although serological persistence is evident, no significant HBV-related disease has been observed, except in patients coinfected with delta virus. Consistently less data are available for HBsAg negative recipients, although they are mostly promising. HBsAg-positive grafts could be an additional organ source for liver transplantation, provided that the risk of reinfection/reactivation is properly prevented.

Diagnosis of herpes simplex virus infection by immunofluorescence.

PubMed Central

Taber, L H; Brasier, F; Couch, R B; Greenberg, S B; Jones, D; Knight, V

1976-01-01

The utility of the indirect immunofluorescent antibody (IFA) technique for diagnosis of herpes simplex virus (HSV) infection was examined by testing specimens for this agent from 31 patients with encephalitis or meningitis, 17 with conjunctivitis, 19 with genital disease, and 1 with genital disease and meningitis. Brain biopsy tissue from four patients with encephalitis was positive by IFA and virus culture for HSV. Leukocytes in cerebrospinal fluid from these four patients and one with HSV meningitis were also positive by IFA, but virus isolation attempts on the fluid were all negative. Conjunctival scrapings from two patients with conjunctivitis were positive for HSV by both IFA and virus culture. Eleven of 12 culture-positive lesions of herpes progenitalis were positive by IFA, and 1 dark field-positive syphilitic chancre was also positive for HSV by both IFA and culture. Evidence for specificity of the results was provided by internal controls in each test and negative results from patients with other diagnoses. Thus, the IFA technique constituted a rapid, sensitive, and specific diagnostic method for the diagnosis of HSV infections. PMID:178689

Characterization of a novel single-stranded RNA virus, closely related to fusariviruses, infecting the plant pathogenic fungus Alternaria brassicicola.

PubMed

Zhong, Jie; Shang, Hong Hong; Zhu, Chuan Xia; Zhu, Jun Zi; Zhu, Hong Jian; Hu, Yan; Gao, Bi Da

2016-06-02

The alternaria blackspot of rapeseed is one of the most prominent diseases of rapeseed. It is caused by three species of the genus Alternaria: Alternaria brassicicola, Alternaria brassicae, and Alternaria raphanin. Here we report a novel positive-sense RNA virus from an A. brassicicola strain 817-14. The virus has a 6639 nucleotide (nt) long genome, excluding a poly (A)-tail, and was predicted to contain three putative open reading frames (ORF1, ORF2, and ORF3). The large ORF1 encoded a 174-kDa polyprotein (composed of 1522 amino acid residues) containing a conserved RNA-dependent RNA polymerase (RdRp) domain and a helicase domain. The other two smaller ORFs encoded polypeptides with unknown function. Homology search and phylogenetic analysis, based on the RdRp and helicase domains, suggest that this virus is related to and grouped with Sclerotinia sclerotiorum fusarivirus 1 (SsFV1), Rosellinia necatrix fusarivirus 1 (RnFV1), Fusarium graminearum virus-DK21 (FgV1), and Penicillium roqueforti RNA mycovirus 1 (PrRV1), all of which belong to a newly proposed family Fusariviridae. For this study, we designed the virus as "Alternaria brassicicola fusarivirus 1" (AbFV1). Virus elimination revealed that AbFV1 has no conspicuous impact on the biological properties of its host. Copyright © 2016. Published by Elsevier B.V.

Significance of bacteria and viruses in the carbon flow of tropical freshwater impoundments

NASA Astrophysics Data System (ADS)

Peduzzi, P.; Schiemer, F.

2003-04-01

In two types of tropical freshwater impoundments, free and particle-attached bacterial abundance and production as well as virus abundance, frequency of viral infection and virus production were investigated together with a set of environmental factors during two characteristic seasons. Organic nitrogen, phosphorus species, dissolved organic carbon and suspended solids were elevated in the wind-mixed water body of a shallow reservoir during the dry season, whereas a deeper reservoir type exhibited no obvious seasonality in these parameters. In SYBR GREEN-stained samples, bacterial abundance showed no seasonal pattern in either reservoir type. A large proportion of the overall bacterial production was associated with particulate material. Highest densities of virus particles and elevated frequency of bacteria containing mature phages were observed in the shallow reservoir during the dry season. The specific bacterial production was related to the abundance of particulate organic matter, phosphorus species and organic nitrogen. Most virus parameters were positively linked to bacterial density, production and to organic nitrogen. We calculated that between 13.2 and 46.1% of the bacterial standing stocks would be subjected to virus-mediated mortality. Carbon budgets for the microbial and organic matter compartments of these tropical freshwater reservoirs indicate prevailing autotrophy and a substantial pathway through the viral shunt. During the dry season the shallow, wind-mixed reservoir provided favorable conditions for bacterial growth and virus propagation.

[Nosocomial infections due to human coronaviruses in the newborn].

PubMed

Gagneur, A; Legrand, M C; Picard, B; Baron, R; Talbot, P J; de Parscau, L; Sizun, J

2002-01-01

Human coronaviruses, with two known serogroups named 229-E and OC-43, are enveloped positive-stranded RNA viruses. The large RNA is surrounded by a nucleoprotein (protein N). The envelop contains 2 or 3 glycoproteins: spike protein (or protein S), matrix protein (or protein M) and a hemagglutinin (or protein HE). Their pathogen role remains unclear because their isolation is difficult. Reliable and rapid methods as immunofluorescence with monoclonal antibodies and reverse transcription-polymerase chain reaction allow new researches on epidemiology. Human coronaviruses can survive for as long as 6 days in suspension and 3 hours after drying on surfaces, suggesting that they could be a source of hospital-acquired infections. Two prospective studies conducted in a neonatal and paediatric intensive care unit demonstrated a significant association of coronavirus-positive nasopharyngal samples with respiratory illness in hospitalised preterm neonates. Positive samples from staff suggested either a patient-to-staff or a staff-to-patient transmission. No cross-infection were observed from community-acquired respiratory-syncitial virus or influenza-infected children to neonates. Universal precautions with hand washing and surface desinfection could be proposed to prevent coronavirus transmission.

Vectorization of transport and diffusion computations on the CDC Cyber 205

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abu-Shumays, I.K.

1986-01-01

The development and testing of alternative numerical methods and computational algorithms specifically designed for the vectorization of transport and diffusion computations on a Control Data Corporation (CDC) Cyber 205 vector computer are described. Two solution methods for the discrete ordinates approximation to the transport equation are summarized and compared. Factors of 4 to 7 reduction in run times for certain large transport problems were achieved on a Cyber 205 as compared with run times on a CDC-7600. The solution of tridiagonal systems of linear equations, central to several efficient numerical methods for multidimensional diffusion computations and essential for fluid flowmore » and other physics and engineering problems, is also dealt with. Among the methods tested, a combined odd-even cyclic reduction and modified Cholesky factorization algorithm for solving linear symmetric positive definite tridiagonal systems is found to be the most effective for these systems on a Cyber 205. For large tridiagonal systems, computation with this algorithm is an order of magnitude faster on a Cyber 205 than computation with the best algorithm for tridiagonal systems on a CDC-7600.« less

Human Cytomegalovirus UL99-Encoded pp28 Is Required for the Cytoplasmic Envelopment of Tegument-Associated Capsids

PubMed Central

Silva, Maria C.; Yu, Qian-Chun; Enquist, Lynn; Shenk, Thomas

2003-01-01

The human cytomegalovirus UL99-encoded pp28 is a myristylated phosphoprotein that is a constituent of the virion. The pp28 protein is positioned within the tegument of the virus particle, a protein structure that resides between the capsid and envelope. In the infected cell, pp28 is found in a cytoplasmic compartment derived from the Golgi apparatus, where the virus buds into vesicles to acquire its final membrane. We have constructed two mutants of human cytomegalovirus that fail to produce the pp28 protein, a substitution mutant (BADsubUL99) and a point mutant (BADpmUL99), and we have propagated them by complementation in pp28-expressing fibroblasts. Both mutant viruses are profoundly defective for growth in normal fibroblasts; no infectious virus could be detected after infection. Whereas normal levels of viral DNA and late proteins were observed in mutant virus-infected cells, large numbers of tegument-associated capsids accumulated in the cytoplasm that failed to acquire an envelope. We conclude that pp28 is required for the final envelopment of the human cytomegalovirus virion in the cytoplasm. PMID:12970444

Development of a challenge-protective vaccine concept by modification of the viral RNA-dependent RNA polymerase of canine distemper virus.

PubMed

Silin, D; Lyubomska, O; Ludlow, M; Duprex, W P; Rima, B K

2007-12-01

We demonstrate that insertion of the open reading frame of enhanced green fluorescent protein (EGFP) into the coding sequence for the second hinge region of the viral L (large) protein (RNA-dependent RNA polymerase) attenuates a wild-type canine distemper virus. Moreover, we show that single intranasal immunization with this recombinant virus provides significant protection against challenge with the virulent parental virus. Protection against wild-type challenge was gained either after recovery of cellular immunity postimmunization or after development of neutralizing antibodies. Insertion of EGFP seems to result in overattenuation of the virus, while our previous experiments demonstrated that the insertion of an epitope tag into a similar position did not affect L protein function. Thus, a desirable level of attenuation could be reached by manipulating the length of the insert (in the second hinge region of the L protein), providing additional tools for optimization of controlled attenuation. This strategy for controlled attenuation may be useful for a "quick response" in vaccine development against well-known and "new" viral infections and could be combined efficiently with other strategies of vaccine development and delivery systems.

A large-scale serological survey of Akabane virus infection in cattle, yak, sheep and goats in China.

PubMed

Wang, Jidong; Blasdell, Kim R; Yin, Hong; Walker, Peter J

2017-08-01

Akabane virus (AKAV) is a member of the Simbu serogroup, classified in the genus Orthobunyavirus, family Bunyaviridae. AKAV infection can cause abortion, stillbirth, and congenital arthrogryposis and hydranencephaly in cattle and sheep. The distribution and prevalence of AKAV infection in China is still unknown. A total of 2731 sera collected from 2006 to 2015 in 24 provinces of China from cattle, sheep, goats and yak were examined by serum neutralisation test. The overall seroprevalence rates for AKAV antibodies were 21.3% in cattle (471/2215) and 12.0% (17/142) in sheep or goats, and 0% in yak (0/374). The results indicated widespread AKAV infection in China among cattle and sheep but yak appear to have a low risk of infection. Using a selection of 50 AKAV-positive and 25 AKAV-negative cattle sera, neutralisation tests were also conducted to detect antibodies to several other Simbu serogroup bunyaviruses and closely related Leanyer virus. Although inconclusive, the data suggest that both Aino virus and Peaton virus, which have been reported previously in Japan and Korea, may also be present in cattle in China. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Distinct DNA exit and packaging portals in the virus Acanthamoeba polyphaga mimivirus.

PubMed

Zauberman, Nathan; Mutsafi, Yael; Halevy, Daniel Ben; Shimoni, Eyal; Klein, Eugenia; Xiao, Chuan; Sun, Siyang; Minsky, Abraham

2008-05-13

Icosahedral double-stranded DNA viruses use a single portal for genome delivery and packaging. The extensive structural similarity revealed by such portals in diverse viruses, as well as their invariable positioning at a unique icosahedral vertex, led to the consensus that a particular, highly conserved vertex-portal architecture is essential for viral DNA translocations. Here we present an exception to this paradigm by demonstrating that genome delivery and packaging in the virus Acanthamoeba polyphaga mimivirus occur through two distinct portals. By using high-resolution techniques, including electron tomography and cryo-scanning electron microscopy, we show that Mimivirus genome delivery entails a large-scale conformational change of the capsid, whereby five icosahedral faces open up. This opening, which occurs at a unique vertex of the capsid that we coined the "stargate", allows for the formation of a massive membrane conduit through which the viral DNA is released. A transient aperture centered at an icosahedral face distal to the DNA delivery site acts as a non-vertex DNA packaging portal. In conjunction with comparative genomic studies, our observations imply a viral packaging pathway akin to bacterial DNA segregation, which might be shared by diverse internal membrane-containing viruses.

Distinct DNA Exit and Packaging Portals in the Virus Acanthamoeba polyphaga mimivirus

PubMed Central

Zauberman, Nathan; Mutsafi, Yael; Halevy, Daniel Ben; Shimoni, Eyal; Klein, Eugenia; Xiao, Chuan; Sun, Siyang; Minsky, Abraham

2008-01-01

Icosahedral double-stranded DNA viruses use a single portal for genome delivery and packaging. The extensive structural similarity revealed by such portals in diverse viruses, as well as their invariable positioning at a unique icosahedral vertex, led to the consensus that a particular, highly conserved vertex-portal architecture is essential for viral DNA translocations. Here we present an exception to this paradigm by demonstrating that genome delivery and packaging in the virus Acanthamoeba polyphaga mimivirus occur through two distinct portals. By using high-resolution techniques, including electron tomography and cryo-scanning electron microscopy, we show that Mimivirus genome delivery entails a large-scale conformational change of the capsid, whereby five icosahedral faces open up. This opening, which occurs at a unique vertex of the capsid that we coined the “stargate”, allows for the formation of a massive membrane conduit through which the viral DNA is released. A transient aperture centered at an icosahedral face distal to the DNA delivery site acts as a non-vertex DNA packaging portal. In conjunction with comparative genomic studies, our observations imply a viral packaging pathway akin to bacterial DNA segregation, which might be shared by diverse internal membrane–containing viruses. PMID:18479185

Chikungunya virus RNA and antibody testing at a National Reference Laboratory since the emergence of Chikungunya virus in the Americas.

PubMed

Prince, Harry E; Seaton, Brent L; Matud, Jose L; Batterman, Hollis J

2015-03-01

Since first reported in the Americas in December 2013, chikungunya virus (CHIKV) infections have been documented in travelers returning from the Caribbean, with many cases identified by CHIKV antibody and/or RNA testing at our laboratory. We used our large data set to characterize the relationship between antibody titers and RNA detection and to estimate IgM persistence. CHIKV RNA was measured by nucleic acid amplification and CHIKV IgG/IgM by indirect immunofluorescence. Of the 1,306 samples submitted for RNA testing in January through September 2014, 393 (30%) were positive; for 166 RNA-positive samples, CHIKV antibody testing was also ordered, and 84% were antibody negative. Of the 6,971 sera submitted for antibody testing in January through September 2014, 1,811 (26%) were IgM positive; 1,461 IgM positives (81%) were also IgG positive. The relationship between the CHIKV antibody titers and RNA detection was evaluated using 376 IgM-positive samples (138 with RNA testing ordered and 238 deidentified and tested for RNA). RNA detection showed no significant association with the IgM titer but was inversely related to the IgG titer; 63% of the IgG negative sera were RNA positive, compared to 36% of sera with low IgG titers (1:10 to 1:80) and 16% with IgG titers of ≥1:160. Using second-sample results from 62 seroconverters, we estimated that CHIKV IgM persists for 110 days (95% confidence interval, 78 to 150 days) after the initial antibody-negative sample. These findings indicate that (i) RNA detection is more sensitive than antibody detection early in CHIKV infection, (ii) in the absence of RNA results, the IgG titer of the IgM-positive samples may be a useful surrogate for viremia, and (iii) CHIKV IgM persists for approximately 4 months after symptom onset. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions.

PubMed

Al-Mulla, Hawaa M N; Turrell, Lauren; Smith, Nicola M; Payne, Luke; Baliji, Surendranath; Züst, Roland; Thiel, Volker; Baker, Susan C; Siddell, Stuart G; Neuman, Benjamin W

2014-04-01

Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs under low-temperature growth conditions. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative reverse transcriptase PCR (RT-PCR) confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher fitness than wild-type virus at the reduced temperature, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during infection with positive-stranded RNA virus. IMPORTANCE The viruses that cause severe acute respiratory syndrome (SARS), poliomyelitis, and hepatitis C all replicate in double-membrane vesicles (DMVs). The big question about DMVs is why they exist in the first place. In this study, we looked at thousands of infected cells and identified two coronavirus mutants that made half as many organelles as normal and two others that made typical numbers but smaller organelles. Despite differences in DMV size and number, all four mutants replicated as efficiently as wild-type virus. To better understand the relative importance of replicative organelles, we carried out competitive fitness experiments. None of these viruses was found to be significantly less fit than wild-type, and two were actually fitter in tests in two kinds of cells. This suggests that viruses have evolved to have tremendous plasticity in the ability to form membrane-associated replication complexes and that large and numerous DMVs are not exclusively associated with efficient coronavirus replication.

Physicochemical Study of Viral Nanoparticles at the Air/Water Interface.

PubMed

Torres-Salgado, Jose F; Comas-Garcia, Mauricio; Villagrana-Escareño, Maria V; Durán-Meza, Ana L; Ruiz-García, Jaime; Cadena-Nava, Ruben D

2016-07-07

The assembly of most single-stranded RNA (ssRNA) viruses into icosahedral nucleocapsids is a spontaneous process driven by protein-protein and RNA-protein interactions. The precise nature of these interactions results in the assembly of extremely monodisperse and structurally indistinguishable nucleocapsids. In this work, by using a ssRNA plant virus (cowpea chlorotic mottle virus [CCMV]) as a charged nanoparticle we show that the diffusion of these nanoparticles from the bulk solution to the air/water interface is an irreversible adsorption process. By using the Langmuir technique, we measured the diffusion and adsorption of viral nucleocapsids at the air/water interface at different pH conditions. The pH changes, and therefore in the net surface charge of the virions, have a great influence in the diffusion rate from the bulk solution to the air/water interface. Moreover, assembly of mesoscopic and microscopic viral aggregates at this interface depends on the net surface charge of the virions and the surface pressure. By using Brewster's angle microscopy we characterized these structures at the interface. Most common structures observed were clusters of virions and soap-frothlike micron-size structures. Furthermore, the CCMV films were compressed to form monolayers and multilayers from moderate to high surface pressures, respectively. After transferring the films from the air/water interface onto mica by using the Langmuir-Blodgett technique, their morphology was characterized by atomic force microscopy. These viral monolayers showed closed-packing nano- and microscopic arrangements.

Update: Ongoing Zika Virus Transmission - Puerto Rico, November 1, 2015-July 7, 2016.

PubMed

Adams, Laura; Bello-Pagan, Melissa; Lozier, Matthew; Ryff, Kyle R; Espinet, Carla; Torres, Jomil; Perez-Padilla, Janice; Febo, Mitchelle Flores; Dirlikov, Emilio; Martinez, Alma; Munoz-Jordan, Jorge; Garcia, Myriam; Segarra, Marangely Olivero; Malave, Graciela; Rivera, Aidsa; Shapiro-Mendoza, Carrie; Rosinger, Asher; Kuehnert, Matthew J; Chung, Koo-Whang; Pate, Lisa L; Harris, Angela; Hemme, Ryan R; Lenhart, Audrey; Aquino, Gustavo; Zaki, Sherif; Read, Jennifer S; Waterman, Stephen H; Alvarado, Luisa I; Alvarado-Ramy, Francisco; Valencia-Prado, Miguel; Thomas, Dana; Sharp, Tyler M; Rivera-Garcia, Brenda

2016-08-05

Zika virus is a flavivirus transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes, and infection can be asymptomatic or result in an acute febrile illness with rash (1). Zika virus infection during pregnancy is a cause of microcephaly and other severe birth defects (2). Infection has also been associated with Guillain-Barré syndrome (GBS) (3) and severe thrombocytopenia (4,5). In December 2015, the Puerto Rico Department of Health (PRDH) reported the first locally acquired case of Zika virus infection. This report provides an update to the epidemiology of and public health response to ongoing Zika virus transmission in Puerto Rico (6,7). A confirmed case of Zika virus infection is defined as a positive result for Zika virus testing by reverse transcription-polymerase chain reaction (RT-PCR) for Zika virus in a blood or urine specimen. A presumptive case is defined as a positive result by Zika virus immunoglobulin M (IgM) enzyme-linked immunosorbent assay (MAC-ELISA)* and a negative result by dengue virus IgM ELISA, or a positive test result by Zika IgM MAC-ELISA in a pregnant woman. An unspecified flavivirus case is defined as positive or equivocal results for both Zika and dengue virus by IgM ELISA. During November 1, 2015-July 7, 2016, a total of 23,487 persons were evaluated by PRDH and CDC Dengue Branch for Zika virus infection, including asymptomatic pregnant women and persons with signs or symptoms consistent with Zika virus disease or suspected GBS; 5,582 (24%) confirmed and presumptive Zika virus cases were identified. Persons with Zika virus infection were residents of 77 (99%) of Puerto Rico's 78 municipalities. During 2016, the percentage of positive Zika virus infection cases among symptomatic males and nonpregnant females who were tested increased from 14% in February to 64% in June. Among 9,343 pregnant women tested, 672 had confirmed or presumptive Zika virus infection, including 441 (66%) symptomatic women and 231 (34%) asymptomatic women. One patient died after developing severe thrombocytopenia (4). Evidence of Zika virus infection or recent unspecified flavivirus infection was detected in 21 patients with confirmed GBS. The widespread outbreak and accelerating increase in the number of cases in Puerto Rico warrants intensified vector control and personal protective behaviors to prevent new infections, particularly among pregnant women.

A prospective study evaluating duration of swine breeding herd PRRS virus-free status and its relationship with measured risk.

PubMed

Holtkamp, Derald J; Yeske, Paul E; Polson, Dale D; Melody, Jamie L; Philips, Reid C

2010-09-01

A variety of methods for eliminating the PRRS virus from pig production sites have been successfully applied. However, success in maintaining a PRRS virus-free status for extended periods of time following elimination has been inconsistent and unpredictable. The objective of this study was to evaluate whether risks measured using version 1 of the American Association of Swine Veterinarians (AASV) PRRS Risk Assessment for the Breeding Herd, season of year and method by which swine breeding herd sites were established PRRS virus-free were associated with how long they retained their virus-free status. Thirty-three swine farrow-to-wean breeding herd sites that were established as PRRS virus-free by either populating a new site with virus-free breeding animals or by completely depopulating the site and repopulating with PRRS virus-free breeding animals were enrolled in this study. Survival analysis, using the Cox proportional hazards model and Kaplan-Meier survival curves, was performed where the outcome was the duration of time PRRS virus-free breeding herd sites remained virus-free ("survived"). Covariates evaluated included the internal and external risk scores measured by the PRRS Risk Assessment for the Breeding Herd as well as the season and the method by which the site was established free of the PRRS virus. All but 5 (15%) of the 33 sites became positive to the PRRS virus during the course of the study and approximately 40% became positive within 1 year from when they were established free of the PRRS virus. A higher external risk score was associated with a greater risk of becoming positive to the PRRS virus and shorter survival times. The internal risk score was not significantly associated with survival. Establishing breeding herd sites free of the PRRS virus in winter months (November through February) was associated with a greater risk of becoming positive to the PRRS virus and shorter survival times compared to those established in non-winter months. The association between the risk of becoming positive to the PRRS virus and the external risk score was confounded by the method the site was established PRRS virus-free. 2010 Elsevier B.V. All rights reserved.

Immunohistochemical analysis of the novel marginal zone B-cell marker IRTA1 in malignant lymphoma.

PubMed

Ikeda, Jun-Ichiro; Kohara, Masaharu; Tsuruta, Yoko; Nojima, Satoshi; Tahara, Shinichiro; Ohshima, Kenji; Kurashige, Masako; Wada, Naoki; Morii, Eiichi

2017-01-01

Marginal zone lymphoma (MZL) is a low-grade B-cell lymphoma derived from marginal zone B cells. Because of a lack of specific immunohistochemical markers, MZL is mainly diagnosed based on the cytological appearance and growth pattern of the tumor. Marginal zone B cells were recently shown to selectively express immunoglobulin superfamily receptor translocation-associated 1 (IRTA1), but the antibody used in that study is not commercially available. We therefore investigated the IRTA1 expression in nonneoplastic lymphoid tissues and 261 malignant lymphomas, examining the ability of a commercially available antibody to accurately diagnose MZL. Among 37 MZLs, 23 of 25 extranodal MZLs of mucosa-associated lymphoid tissue (MALT lymphomas), 3 of 6 splenic MZLs and 3 of 6 nodal MZLs were positive for IRTA1. Among the 98 diffuse large B-cell lymphomas, 33 were positive for IRTA1, including 1 of 38 follicular lymphomas, and all precursor B-lymphoblastic (2/2) and T-lymphoblastic (7/7) leukemia/lymphomas. Other mature B-cell and T-cell lymphomas, and Hodgkin lymphoma were negative for IRTA1. In MALT lymphoma, positive cells were detected mainly in intraepithelial and subepithelial marginal zone B cells. In 1 case of grade 3 follicular lymphoma, IRTA1 was also expressed in the area of large cell transformation. When tumors were classified as germinal center B cell-like (GCB) or non-GCB using the algorithm of Hans, positive expression of IRTA1 was correlated significantly with non-GCB diffuse large B-cell lymphomas (P < .05). These results demonstrated the ability of the commercially available IRTA1 antibody to distinguish MALT lymphoma from other low-grade B-cell lymphomas. Copyright © 2016 Elsevier Inc. All rights reserved.

Inter-Agency Collaboration between a Clinical Early Intervention Program and a Residential Care Setting To Meet the Needs of a Toddler.

ERIC Educational Resources Information Center

Herz, Susan; And Others

This paper discusses the interagency collaboration between a clinical assessment and intervention program for toddlers offered through the psychiatry department of a large metropolitan west coast medical center and a group home for infants and young children who are positive for the human immunodeficiency virus (HIV). The paper presents the case…

Comparative Study of Broadband Photometry Relations for Ultra-Diffuse and Normal Galaxies in the Coma Cluster

NASA Astrophysics Data System (ADS)

Stone, Maria Babakhanyan

Ultra-diffuse galaxies are a novel type of galaxies discovered first in the Coma cluster. These objects are characterized simultaneously by large sizes and by very low counts of constituent stars. Conflicting theories have been proposed to explain how these large diffuse galaxies could have survived in the harsh environment of clusters. To date, thousands of these new galaxies have been identified in cluster environments. However, further studies are required to understand their relationship to the known giant and dwarf classes of galaxies. The purpose of this study is to compare the trends of inner and outer populations of normal members of the Coma cluster and ultra-diffuse galaxies in color-magnitude space. The present work used several astronomical catalogs to identify the member galaxies based on the coordinates of their positions and to extract available colors and magnitudes. We obtained correlations to convert colors and magnitudes from different systems into the common Sloan Digital Sky Survey system to facilitate the comparative analysis. We showed the quantitative relations describing the color-magnitude trends of galaxies in the core and the outskirts of the cluster. We confirmed that the inner and outer populations of ultra-diffuse galaxies exhibit an offset similar to the normal red sequence galaxies. We presented an initial assessment of stellar population ages and metallicities which correspond to the obtained color offsets. We surveyed the available images of the cluster for outliers, merger candidates, and candidate ultra-diffuse galaxies. We conclude that ultra-diffuse galaxies are an important part of the Coma cluster evolutionary history and future work is needed especially in obtaining spectroscopic data of a larger number of these dim galaxies.

Rapid Tests and the Diagnosis of Visceral Leishmaniasis and Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Coinfection.

PubMed

Barbosa Júnior, Walter Lins; Ramos de Araújo, Paulo Sérgio; Dias de Andrade, Luiz; Aguiar Dos Santos, Ana Maria; Lopes da Silva, Maria Almerice; Dantas-Torres, Filipe; Medeiros, Zulma

2015-11-01

After the emergence of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis (VL)-HIV/AIDS coinfections has increased worldwide. Herein, we assessed the usefulness of an rK39-based immunochromatographic test (rK39 ICT) (DiaMed-IT LEISH(®); DiaMed AG, Cressier-sur-Morat, Switzerland) and a latex agglutination test (KAtex; Kalon Biological, Guildford, United Kingdom) for urinary antigen detection to diagnose VL in 15 HIV/AIDS patients from northeastern Brazil. VL diagnosis was based on clinical findings, cytology, serology, parasite DNA, and/or urinary antigen detection. VL was confirmed in seven out of 15 HIV/AIDS patients. Only three patients were positive in bone marrow cytology, three patients were conventional polymerase chain reaction (PCR) positive, while six were real-time PCR positive. All patients were direct agglutination test (DAT) (Royal Tropical Institute, Amsterdam, The Netherlands) positive; of these, four were positive by rK39 ICT and five by KAtex. Large-scale studies are needed to validate the use of the KAtex in the national public health laboratory network in Brazil, aiming at improving the diagnosis of VL in HIV/AIDS patients in this country. © The American Society of Tropical Medicine and Hygiene.

The Honey Bee Pathosphere of Mongolia: European Viruses in Central Asia.

PubMed

Tsevegmid, Khaliunaa; Neumann, Peter; Yañez, Orlando

2016-01-01

Parasites and pathogens are apparent key factors for the detrimental health of managed European honey bee subspecies, Apis mellifera. Apicultural trade is arguably the main factor for the almost global distribution of most honey bee diseases, thereby increasing chances for multiple infestations/infections of regions, apiaries, colonies and even individual bees. This imposes difficulties to evaluate the effects of pathogens in isolation, thereby creating demand to survey remote areas. Here, we conducted the first comprehensive survey for 14 honey bee pathogens in Mongolia (N = 3 regions, N = 9 locations, N = 151 colonies), where honey bee colonies depend on humans to overwinter. In Mongolia, honey bees, Apis spp., are not native and colonies of European A. mellifera subspecies have been introduced ~60 years ago. Despite the high detection power and large sample size across Mongolian regions with beekeeping, the mite Acarapis woodi, the bacteria Melissococcus plutonius and Paenibacillus larvae, the microsporidian Nosema apis, Acute bee paralysis virus, Kashmir bee virus, Israeli acute paralysis virus and Lake Sinai virus strain 2 were not detected, suggesting that they are either very rare or absent. The mite Varroa destructor, Nosema ceranae and four viruses (Sacbrood virus, Black queen cell virus, Deformed wing virus (DWV) and Chronic bee paralysis virus) were found with different prevalence. Despite the positive correlation between the prevalence of V. destructor mites and DWV, some areas had only mites, but not DWV, which is most likely due to the exceptional isolation of apiaries (up to 600 km). Phylogenetic analyses of the detected viruses reveal their clustering and European origin, thereby supporting the role of trade for pathogen spread and the isolation of Mongolia from South-Asian countries. In conclusion, this survey reveals the distinctive honey bee pathosphere of Mongolia, which offers opportunities for exciting future research.

The Honey Bee Pathosphere of Mongolia: European Viruses in Central Asia

PubMed Central

Tsevegmid, Khaliunaa; Neumann, Peter; Yañez, Orlando

2016-01-01

Parasites and pathogens are apparent key factors for the detrimental health of managed European honey bee subspecies, Apis mellifera. Apicultural trade is arguably the main factor for the almost global distribution of most honey bee diseases, thereby increasing chances for multiple infestations/infections of regions, apiaries, colonies and even individual bees. This imposes difficulties to evaluate the effects of pathogens in isolation, thereby creating demand to survey remote areas. Here, we conducted the first comprehensive survey for 14 honey bee pathogens in Mongolia (N = 3 regions, N = 9 locations, N = 151 colonies), where honey bee colonies depend on humans to overwinter. In Mongolia, honey bees, Apis spp., are not native and colonies of European A. mellifera subspecies have been introduced ~60 years ago. Despite the high detection power and large sample size across Mongolian regions with beekeeping, the mite Acarapis woodi, the bacteria Melissococcus plutonius and Paenibacillus larvae, the microsporidian Nosema apis, Acute bee paralysis virus, Kashmir bee virus, Israeli acute paralysis virus and Lake Sinai virus strain 2 were not detected, suggesting that they are either very rare or absent. The mite Varroa destructor, Nosema ceranae and four viruses (Sacbrood virus, Black queen cell virus, Deformed wing virus (DWV) and Chronic bee paralysis virus) were found with different prevalence. Despite the positive correlation between the prevalence of V. destructor mites and DWV, some areas had only mites, but not DWV, which is most likely due to the exceptional isolation of apiaries (up to 600 km). Phylogenetic analyses of the detected viruses reveal their clustering and European origin, thereby supporting the role of trade for pathogen spread and the isolation of Mongolia from South-Asian countries. In conclusion, this survey reveals the distinctive honey bee pathosphere of Mongolia, which offers opportunities for exciting future research. PMID:26959221

Oncolytic Adenoviruses Targeted to Human Papilloma Virus-Positive Head and Neck Squamous Cell Carcinomas

PubMed Central

LaRocca, Christopher J.; Han, Joohee; Oliveira, Amanda R.; Davydova, Julia; Herzberg, Mark; Gopalakrishnan, Rajaram; Yamamoto, Masato

2016-01-01

Objectives In recent years, the incidence of Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) has markedly increased. Our aim was to design a novel therapeutic agent through the use of conditionally replicative adenoviruses (CRAds) that are targeted to the HPV E6 and E7 oncoproteins. Methods Each adenovirus included small deletion(s) in the E1a region of the genome (Δ24 or CB016) intended to allow for selective replication in HPV-positive cells. In vitro assays were performed to analyze the transduction efficiency of the vectors and the cell viability following viral infection. Then, the UPCI SCC 090 cell line (HPV-positive) was used to establish subcutaneous tumors in the flanks of nude mice. The tumors were then treated with either one dose of the virus or four doses (injected every fourth day). Results The transduction analysis with luciferase-expressing viruses demonstrated that the 5/3 fiber modification maximized virus infectivity. In vitro, both viruses (5/3Δ24 and 5/3CB016) demonstrated profound oncolytic effects. The 5/3CB016 virus was selective for only HPV-positive HNSCC cells, whereas the 5/3Δ24 virus killed HNSCC cells regardless of HPV status. In vivo, single injections of both viruses demonstrated anti-tumor effects until only 6–8 days following viral inoculation. However, after four viral injections, there was statistically significant reduction in tumor growth when compared to the control group (p<0.05). Conclusion CRAds targeted to HPV-positive HNSCCs demonstrated excellent in vitro and in vivo therapeutic effects, and they have the potential to be clinically translated as a novel treatment modality for this emerging disease. PMID:27086483

Low impact of infectious hypodermal and hematopoietic necrosis virus (IHHNV) on growth and reproductive performance of Penaeus monodon.

PubMed

Withyachumnarnkul, Boonsirm; Chayaburakul, Kanokporn; Lao-Aroon, Supak; Plodpai, Pornthep; Sritunyalucksana, Kallaya; Nash, Gary

2006-04-06

No controlled studies on the effect of infectous hypodermal and necrosis virus (IHHNV) on Penaeus monodon have been previously reported. Here we describe domesticated P. monodon that became positive for IHHNV and other viruses at variable levels of prevalence during cultivation in 16 open-air, earthen ponds. These were stocked with domesticated postlarvae (PL) that tested negative for 7 shrimp viruses including IHHNV at 6% prevalence in 3 checks using polymerase chain reaction (PCR) methods. These PL were derived from domesticated female broodstock that individually tested negative for the same viruses. At 4 mo of culture, the shrimp in some ponds without obvious mortality tested positive by PCR methods for IHHNV and 3 other viruses at variable levels of maximum estimated prevalence (MEP). Stained tissue sections showed no lesions typical of IHHNV, but in situ hybridization tests with an IHHNV-specific DNA probe were positive. There was no significant difference in mean body weight (i.e. ca. 25 g) between shrimp groups positive or negative for IHHNV. Similar results were obtained with IHHNV negative and positive adults at 1 yr. Adults that individually tested negative for all 7 viruses and some that tested lightly positive for IHHNV were bred for the next generation. There were no significant differences in the number of eggs (> 600 000) and nauplii (ca. 300,000) produced by females negative and positive for IHHNV. From these females, 11/49 (22%) IHHNV PCR-positive PL batches were obtained from PCR-negative spawners, while 8/11 (73%) were obtained from IHHNV PCR-positive spawners. The results suggested that IHHNV infection can be transmitted vertically but does not seriously retard growth of P. monodon or affect fecundity of lightly infected broodstock.

Positron Emission Tomography/Computed Tomography Findings During Therapy Predict Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemotherapy Alone but Not in Those Who Receive Consolidation Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org; Hess, Kenneth; Shihadeh, Ferial

2014-06-01

Purpose: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). Methods and Materials: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. Results: Of the 294 patients, 163 (55%) were male, 144more » (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET−) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET− versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET− vs 52% PET+ [P=.012], OS 78% for PET− and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET− vs 81% PET+ [P=.88]; OS 90% PET− vs 81% PET+ [P=.39]). Conclusion: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings.« less

Raw Sewage Harbors Diverse Viral Populations

PubMed Central

Cantalupo, Paul G.; Calgua, Byron; Zhao, Guoyan; Hundesa, Ayalkibet; Wier, Adam D.; Katz, Josh P.; Grabe, Michael; Hendrix, Roger W.; Girones, Rosina; Wang, David; Pipas, James M.

2011-01-01

ABSTRACT At this time, about 3,000 different viruses are recognized, but metagenomic studies suggest that these viruses are a small fraction of the viruses that exist in nature. We have explored viral diversity by deep sequencing nucleic acids obtained from virion populations enriched from raw sewage. We identified 234 known viruses, including 17 that infect humans. Plant, insect, and algal viruses as well as bacteriophages were also present. These viruses represented 26 taxonomic families and included viruses with single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), positive-sense ssRNA [ssRNA(+)], and dsRNA genomes. Novel viruses that could be placed in specific taxa represented 51 different families, making untreated wastewater the most diverse viral metagenome (genetic material recovered directly from environmental samples) examined thus far. However, the vast majority of sequence reads bore little or no sequence relation to known viruses and thus could not be placed into specific taxa. These results show that the vast majority of the viruses on Earth have not yet been characterized. Untreated wastewater provides a rich matrix for identifying novel viruses and for studying virus diversity. Importance At this time, virology is focused on the study of a relatively small number of viral species. Specific viruses are studied either because they are easily propagated in the laboratory or because they are associated with disease. The lack of knowledge of the size and characteristics of the viral universe and the diversity of viral genomes is a roadblock to understanding important issues, such as the origin of emerging pathogens and the extent of gene exchange among viruses. Untreated wastewater is an ideal system for assessing viral diversity because virion populations from large numbers of individuals are deposited and because raw sewage itself provides a rich environment for the growth of diverse host species and thus their viruses. These studies suggest that the viral universe is far more vast and diverse than previously suspected. PMID:21972239

Rapid detection and subtyping of European swine influenza viruses in porcine clinical samples by haemagglutinin- and neuraminidase-specific tetra- and triplex real-time RT-PCRs.

PubMed

Henritzi, Dinah; Zhao, Na; Starick, Elke; Simon, Gaelle; Krog, Jesper S; Larsen, Lars Erik; Reid, Scott M; Brown, Ian H; Chiapponi, Chiara; Foni, Emanuela; Wacheck, Silke; Schmid, Peter; Beer, Martin; Hoffmann, Bernd; Harder, Timm C

2016-11-01

A diversifying pool of mammalian-adapted influenza A viruses (IAV) with largely unknown zoonotic potential is maintained in domestic swine populations worldwide. The most recent human influenza pandemic in 2009 was caused by a virus with genes originating from IAV isolated from swine. Swine influenza viruses (SIV) are widespread in European domestic pig populations and evolve dynamically. Knowledge regarding occurrence, spread and evolution of potentially zoonotic SIV in Europe is poorly understood. Efficient SIV surveillance programmes depend on sensitive and specific diagnostic methods which allow for cost-effective large-scale analysis. New SIV haemagglutinin (HA) and neuraminidase (NA) subtype- and lineage-specific multiplex real-time RT-PCRs (RT-qPCR) have been developed and validated with reference virus isolates and clinical samples. A diagnostic algorithm is proposed for the combined detection in clinical samples and subtyping of SIV strains currently circulating in Europe that is based on a generic, M-gene-specific influenza A virus RT-qPCR. In a second step, positive samples are examined by tetraplex HA- and triplex NA-specific RT-qPCRs to differentiate the porcine subtypes H1, H3, N1 and N2. Within the HA subtype H1, lineages "av" (European avian-derived), "hu" (European human-derived) and "pdm" (human pandemic A/H1N1, 2009) are distinguished by RT-qPCRs, and within the NA subtype N1, lineage "pdm" is differentiated. An RT-PCR amplicon Sanger sequencing method of small fragments of the HA and NA genes is also proposed to safeguard against failure of multiplex RT-qPCR subtyping. These new multiplex RT-qPCR assays provide adequate tools for sustained SIV monitoring programmes in Europe. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Giants among larges: how gigantism impacts giant virus entry into amoebae.

PubMed

Rodrigues, Rodrigo Araújo Lima; Abrahão, Jônatas Santos; Drumond, Betânia Paiva; Kroon, Erna Geessien

2016-06-01

The proposed order Megavirales comprises the nucleocytoplasmic large DNA viruses (NCLDV), infecting a wide range of hosts. Over time, they co-evolved with different host cells, developing various strategies to penetrate them. Mimiviruses and other giant viruses enter cells through phagocytosis, while Marseillevirus and other large viruses explore endocytosis and macropinocytosis. These differing strategies might reflect the evolution of those viruses. Various scenarios have been proposed for the origin and evolution of these viruses, presenting one of the most enigmatic issues to surround these microorganisms. In this context, we believe that giant viruses evolved independently by massive gene/size gain, exploring the phagocytic pathway of entry into amoebas. In response to gigantism, hosts developed mechanisms to evade these parasites. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Primary diffuse large B-cell lymphoma of the uterus complicated with hydronephrosis].

PubMed

Isosaka, Mai; Hayashi, Toshiaki; Mitsuhashi, Kei; Tanaka, Michihiro; Adachi, Takeya; Kondo, Yoshihiro; Suzuki, Takashi; Shinomura, Yasuhisa

2013-04-01

Malignant lymphoma sometimes originates from extranodal sites; however, the uterus has rarely been reported as the site of the primary lesion. We present a patient with malignant lymphoma of the uterus complicating bilateral hydronephrosis. A 67-year-old previously healthy woman was seen at a clinic because of massive genital bleeding. She was referred to our hospital for further examination of a uterine tumor. Computed tomography scans revealed a pelvic tumor invading to the retroperitoneal region, which caused bilateral obstruction of the ureters and hydronephrosis. No lymph node swelling was detected. Magnetic resonance imaging showed a bulky uterine tumor that was homogenously low on T1-weighted imaging and isointense on T2-weighted imaging, while the endometrium was intact. A pathological examination of the biopsy specimen from the uterine cervix revealed diffuse infiltration of CD20-positive atypical large lymphoid cells, which was compatible with diffuse large B-cell lymphoma (DLBCL). Since the tumor expanded from the uterus and no other abnormal lesion was observed in imaging studies including gallium scintigraphy, a diagnosis of DLBCL of the uterus, clinical stage IE was made. The patient received six cycles of rituximab plus CHOP chemotherapy followed by involved field irradiation. She achieved complete remission and has been alive for more than two years without relapse.

A large new subset of TRIM genes highly diversified by duplication and positive selection in teleost fish

PubMed Central

van der Aa, Lieke M; Levraud, Jean-Pierre; Yahmi, Malika; Lauret, Emilie; Briolat, Valérie; Herbomel, Philippe; Benmansour, Abdenour; Boudinot, Pierre

2009-01-01

Background In mammals, the members of the tripartite motif (TRIM) protein family are involved in various cellular processes including innate immunity against viral infection. Viruses exert strong selective pressures on the defense system. Accordingly, antiviral TRIMs have diversified highly through gene expansion, positive selection and alternative splicing. Characterizing immune TRIMs in other vertebrates may enlighten their complex evolution. Results We describe here a large new subfamily of TRIMs in teleosts, called finTRIMs, identified in rainbow trout as virus-induced transcripts. FinTRIMs are formed of nearly identical RING/B-box regions and C-termini of variable length; the long variants include a B30.2 domain. The zebrafish genome harbors a striking diversity of finTRIMs, with 84 genes distributed in clusters on different chromosomes. A phylogenetic analysis revealed different subsets suggesting lineage-specific diversification events. Accordingly, the number of fintrim genes varies greatly among fish species. Conserved syntenies were observed only for the oldest fintrims. The closest mammalian relatives are trim16 and trim25, but they are not true orthologs. The B30.2 domain of zebrafish finTRIMs evolved under strong positive selection. The positions under positive selection are remarkably congruent in finTRIMs and in mammalian antiviral TRIM5α, concentrated within a viral recognition motif in mammals. The B30.2 domains most closely related to finTRIM are found among NOD-like receptors (NLR), indicating that the evolution of TRIMs and NLRs was intertwined by exon shuffling. Conclusion The diversity, evolution, and features of finTRIMs suggest an important role in fish innate immunity; this would make them the first TRIMs involved in immunity identified outside mammals. PMID:19196451

Novel Neuroimaging Methods to Understand How HIV Affects the Brain

PubMed Central

Thompson, Paul

2015-01-01

In much of the developed world, the HIV epidemic has largely been controlled by anti-retroviral treatment. Even so, there is growing concern that HIV-infected individuals may be at risk for accelerated brain aging, and a range of cognitive impairments. What promotes or resists these changes is largely unknown. There is also interest in discovering factors that promote resilience to HIV, and combat its adverse effects in children. Here we review recent developments in brain imaging that reveal how the virus affects the brain. We relate these brain changes to changes in blood markers, cognitive function, and other patient outcomes or symptoms, such as apathy or neuropathic pain. We focus on new and emerging techniques, including new variants of brain MRI. Diffusion tensor imaging, for example, can map the brain’s structural connections while fMRI can uncover functional connections. Finally, we suggest how large-scale global research alliances, such as ENIGMA, may resolve controversies over effects where evidence is now lacking. These efforts pool scans from tens of thousands of individuals, and offer a source of power not previously imaginable for brain imaging studies. PMID:25902966

Prevalence of human papillomavirus, Epstein-Barr virus, p21, and p53 expression in sinonasal inverted papilloma, nasal polyp, and hypertrophied turbinate in Hong Kong patients.

PubMed

Sham, C L; To, K F; Chan, Paul K S; Lee, Dennis L Y; Tong, Michael C F; van Hasselt, C Andrew

2012-04-01

The purpose of this study of human papillomavirus (HPV), Epstein-Barr virus (EBV), p21, and p53 in sinonasal inverted papilloma (IP) was to help elucidate its pathogenesis. Seventy-three IPs, 48 nasal polyps, and 85 hypertrophied turbinates were subjected to HPV polymerase chain reaction (PCR) study. Seventy-three IPs, 30 nasal polyps, and 32 hypertrophied turbinates were subjected to EBV in situ hybridization (ISH), p21, and p53 immunohistochemical (IHC) studies. HPV was positive in 3 of 73 IPs (4.1%). All specimens were EBV negative. In all, 99% of IPs showed strong and diffuse p21 nuclear reactivity. Most nasal polyps and hypertrophied turbinates showed weak to moderate immunoreactivity of the basal and parabasal cells. Only focal p53 immunoreactivity of the basal and parabasal cells was found in 19% of IPs and 40% of nasal polyps. HPV prevalence of our IP is low. EBV is not present in IP. High p21 and low p53 expression in IP suggests a non-p53-dependent regulation pathway. Copyright © 2011 Wiley Periodicals, Inc.

Molecular Smallpox Vaccine Delivered by Alphavirus Replicons Elicits Protective Immunity in Mice and Non-human Primates

PubMed Central

Hooper, Jay W.; Ferro, Anthony M.; Golden, Joseph W.; Silvera, Peter; Dudek, Jeanne; Alterson, Kim; Custer, Max; Rivers, Bryan; Morris, John; Owens, Gary; Smith, Jonathan F.; Kamrud, Kurt I.

2009-01-01

Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 70s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRP) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 × 106 PFU of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine. PMID:19833247

Influenza activity among the paediatric age group in Chennai.

PubMed

Ramamurty, Nalini; Pillai, Lalitha C; Gunasekaran, P; Elango, Varalakshmi; Priya, Padma; Sheriff, A Khaleefathullah; Mohana

2005-06-01

Respiratory viral infections have a major impact on public health. Acute respiratory infections largely caused by viruses, are the most common illnesses experienced by otherwise healthy adults and children. Among the respiratory viruses, influenza viruses are known to cause outbreaks globally. Information on the activity of influenza virus in our country is limited and none from Chennai. The present study was carried out to isolate and identify the influenza virus serotypes causing acute respiratory infection in children attending a tertiary care centre at Chennai. During January to December 2002, 240 children with acute respiratory infection attending the out patient clinic of Institute of Child Health were included by convenient sampling. Throat swabs were collected from 4 to 5 cases every week. Isolation of influenza virus was attempted by inoculating the sample in Madin Darby Canine Kidney (MDCK) cell line. The isolates were typed by haemagglutination inhibition test and confirmed by immunoflourescence assay. Virus isolation was positive in 30 (12.5%) of the 240 samples. Influenza A/H3N2/Panama/ 2000/99 was the predominant serotype isolated accounting for 24 (80%) of the 30 isolates. Influenza B/Sichuan/379/99 was isolated in 4 (13.33%) and a combination of Influenza A/H3N2 and B/Sichuan in 2 (6.6%) of the isolates. Isolation of influenza A and B viruses indicated a significant activity of these viruses in Chennai. Peak activity was observed during and after the first spell of rain. The predominance of A/H3N2/ Panama is an indication that the Indian scenario is similar to the global picture of influenza activity.

Function of bacterial cells and their exuded extracellular polymeric substances (EPS) in virus removal by red soils.

PubMed

Zhao, Bingzi; Jiang, Yan; Jin, Yan; Zhang, Jiabao

2014-01-01

The potential influence of autochthonous microorganisms on virus fate in soil is usually determined through extreme conditions of sterilization vs. nonsterilization; however, the relative importance of microbial cells and their exudates remains unclear. In this study, bacterial cells (cell) were harvested, and their exuded extracellular polymeric substances (EPS) were extracted from three strains of bacteria, namely, Gram-negative bacteria Pseudomonas putida and Pseudomonas aeruginosa as well as Gram-positive bacterium Bacillus subtilis. This study aimed to evaluate virus removal in solutions in the presence of cell, EPS, and their combination (cell/EPS), as well as to investigate how their presence affects virus removal efficiencies by four red soils based on batch experiments. Results showed that virus removal percentage in solutions ranged from 11 to 23 in the presence of cells only and from 12 to 15 in the presence of EPS only. The removal percentage in the combined cell/EPS treatment can be estimated by summing the results achieved by the cell and EPS treatments, separately. Meanwhile, cell presence had a negligible effect on virus removal by red soils. EPS and combined cell/EPS significantly reduced virus removal by 20 to 69% and 16 to 50%, respectively, which indicated that EPS served a dominant function in reducing virus removal. This study clearly demonstrated that the prediction of virus removal by red soils must consider the effect of bacteria, especially those producing large quantities of EPS, which can be responsible for the underestimation of viral load in certain studies.

The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.

PubMed

van Riel, Debby; Verdijk, Rob; Kuiken, Thijs

2015-01-01

The olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (CNS). Each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. Viruses that can use the olfactory nerve as a shortcut into the CNS include influenza A virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatitis virus, rabies virus, parainfluenza virus, adenoviruses, Japanese encephalitis virus, West Nile virus, chikungunya virus, La Crosse virus, mouse hepatitis virus, and bunyaviruses. However, mechanisms of transport via the olfactory nerve and subsequent spread through the CNS are poorly understood. Proposed mechanisms are either infection of olfactory receptor neurons themselves or diffusion through channels formed by olfactory ensheathing cells. Subsequent virus spread through the CNS could occur by multiple mechanisms, including trans-synaptic transport and microfusion. Viral infection of the CNS can lead to damage from infection of nerve cells per se, from the immune response, or from a combination of both. Clinical consequences range from nervous dysfunction in the absence of histopathological changes to severe meningoencephalitis and neurodegenerative disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morales, George J.; Maggs, James E.

The project expanded and developed mathematical descriptions, and corresponding numerical modeling, of non-diffusive transport to incorporate new perspectives derived from basic transport experiments performed in the LAPD device at UCLA, and at fusion devices throughout the world. By non-diffusive it is meant that the transport of fundamental macroscopic parameters of a system, such as temperature and density, does not follow the standard diffusive behavior predicted by a classical Fokker-Planck equation. The appearance of non-diffusive behavior is often related to underlying microscopic processes that cause the value of a system parameter, at one spatial position, to be linked to distant events,more » i.e., non-locality. In the LAPD experiments the underlying process was traced to large amplitude, coherent drift-waves that give rise to chaotic trajectories. Significant advances were made in this project. The results have lead to a new perspective about the fundamentals of edge transport in magnetically confined plasmas; the insight has important consequences for worldwide studies in fusion devices. Progress was also made in advancing the mathematical techniques used to describe fractional diffusion.« less

Viruses and tetraspanins: lessons from single molecule approaches.

PubMed

Dahmane, Selma; Rubinstein, Eric; Milhiet, Pierre-Emmanuel

2014-05-05

Tetraspanins are four-span membrane proteins that are widely distributed in multi-cellular organisms and involved in several infectious diseases. They have the unique property to form a network of protein-protein interaction within the plasma membrane, due to the lateral associations with one another and with other membrane proteins. Tracking tetraspanins at the single molecule level using fluorescence microscopy has revealed the membrane behavior of the tetraspanins CD9 and CD81 in epithelial cell lines, providing a first dynamic view of this network. Single molecule tracking highlighted that these 2 proteins can freely diffuse within the plasma membrane but can also be trapped, permanently or transiently, in tetraspanin-enriched areas. More recently, a similar strategy has been used to investigate tetraspanin membrane behavior in the context of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection. In this review we summarize the main results emphasizing the relationship in terms of membrane partitioning between tetraspanins, some of their partners such as Claudin-1 and EWI-2, and viral proteins during infection. These results will be analyzed in the context of other membrane microdomains, stressing the difference between raft and tetraspanin-enriched microdomains, but also in comparison with virus diffusion at the cell surface. New advanced single molecule techniques that could help to further explore tetraspanin assemblies will be also discussed.

Distemper: not a new disease in lions and tigers.

PubMed Central

Myers, D L; Zurbriggen, A; Lutz, H; Pospischil, A

1997-01-01

In light of recent canine distemper virus (CDV) epidemics, we set out to determine the historical significance of CDV infection in captive lions and tigers in Switzerland. The retrospective case material consisted of 42 lion and tiger necropsy cases from 1972 to 1992. Necropsy reports for all lions and tigers were reviewed. All existing paraffin tissues were immunohistochemically examined with a polyclonal antibody raised against CDV. The results for 19 of the 42 lions and tigers were classified as positive by immunohistochemistry; 23 results were negative or questionable. The results for four animals (three positive and one negative ) were further tested by in situ hybridization, and the results concurred with the immunohistochemistry findings. CDV infection of large cats is older and more widespread than previously thought. All large cats in captivity should be immunized even if canine distemper is not believed to be a problem for large cats in the area. PMID:9067652

Detection of Viral Pathogens by Reverse Transcriptase PCR and of Microbial Indicators by Standard Methods in the Canals of the Florida Keys

PubMed Central

Griffin, Dale W.; Gibson, Charles J.; Lipp, Erin K.; Riley, Kelley; Paul, John H.; Rose, Joan B.

1999-01-01

In order to assess the microbial water quality in canal waters throughout the Florida Keys, a survey was conducted to determine the concentration of microbial fecal indicators and the presence of human pathogenic microorganisms. A total of 19 sites, including 17 canal sites and 2 nearshore water sites, were assayed for total coliforms, fecal coliforms, Escherichia coli, Clostridium perfringens, enterococci, coliphages, F-specific (F+) RNA coliphages, Giardia lamblia, Cryptosporidium parvum, and human enteric viruses (polioviruses, coxsackie A and B viruses, echoviruses, hepatitis A viruses, Norwalk viruses, and small round-structured viruses). Numbers of coliforms ranged from <1 to 1,410, E. coli organisms from <1 to 130, Clostridium spp. from <1 to 520, and enterococci from <1 to 800 CFU/100 ml of sample. Two sites were positive for coliphages, but no F+ phages were identified. The sites were ranked according to microbial water quality and compared to various water quality standards and guidelines. Seventy-nine percent of the sites were positive for the presence of enteroviruses by reverse transcriptase PCR (polioviruses, coxsackie A and B viruses, and echoviruses). Sixty-three percent of the sites were positive for the presence of hepatitis A viruses. Ten percent of the sites were positive for the presence of Norwalk viruses. Ninety-five percent of the sites were positive for at least one of the virus groups. These results indicate that the canals and nearshore waters throughout the Florida Keys are being impacted by human fecal material carrying human enteric viruses through current wastewater treatment strategies such as septic tanks. Exposure to canal waters through recreation and work may be contributing to human health risks. PMID:10473424

Study on the occurrence of tick-borne encephalitis virus RNA in European bison (Bison bonasus) eliminated at Białowieza Primeval Forest (north-eastern Poland) in 2005-2009.

PubMed

Biernat, Beata; Karbowiak, Grzegorz

2014-01-01

Tick-borne encephalitis virus (TBEV) (Flaviviridae, Flavivirus) is an arthropod-borne virus, an etiologic agent of tick-borne encephalitis (TBE), an infection involving the central nervous system. The disease is endemic in a large region in Eurasia where it is transmitted mainly by Ixodes ricinus in Europe and I. persulcatus ticks in Asia. This is the most important tick-transmitted arbovirus of human pathogenicity in Europe. The Białowieza Primeval Forest is a well-known endemic focus of tick-borne encephalitis. The aim of this study was to identify the prevalence of tickborne encephalitis virus (TBEV) in European bison, the important hosts of ticks in the Białowieza Primeval Forest. In the years 2005-2009, 95 blood samples were collected from European bison and examined for the presence of TBEV using nRT-PCR method. No positive results were obtained. For better understanding of TBEV vertebrate reservoir hosts in Poland, further investigations are needed.

Standing your Ground to Exoribonucleases: Function of Flavivirus Long Non-coding RNAs

PubMed Central

Charley, Phillida A.; Wilusz, Jeffrey

2015-01-01

Members of the Flaviviridae (e.g. Dengue virus, West Nile virus, and Hepatitis C virus) contain a positive-sense RNA genome that encodes a large polyprotein. It is now also clear most if not all of these viruses also produce an abundant subgenomic long non-coding RNA. These non-coding RNAs, which are called subgenomicflavivirus RNAs (sfRNAs) or Xrn1-resistant RNAs (xrRNAs), are stable decay intermediates generated from the viral genomic RNA through the stalling of the cellular exoribonuclease Xrn1 at highly structured regions. Several functions of these flavivirus long non-coding RNAs have been revealed in recent years. The generation of these sfRNAs/xrRNAs from viral transcripts results in the repression of Xrn1 and the dysregulation of cellular mRNA stability. The abundant sfRNAs also serve directly as a decoy for important cellular protein regulators of the interferon and RNA interference antiviral pathways. Thus the generation of long non-coding RNAs from flaviviruses, hepaciviruses and pestiviruses likely disrupts aspects of innate immunity and may directly contribute to viral replication, cytopathology and pathogenesis. PMID:26368052

A novel flavivirus detected in two Aedes spp. collected near the demilitarized zone of the Republic of Korea.

PubMed

Korkusol, Achareeya; Takhampunya, Ratree; Hang, Jun; Jarman, Richard G; Tippayachai, Bousaraporn; Kim, Heung-Chul; Chong, Sung-Tae; Davidson, Silas A; Klein, Terry A

2017-05-01

Flaviviruses comprise a large and diverse group of positive-stranded RNA viruses, including tick-, mosquito- and unknown-vector-borne flaviviruses. A novel flavivirus was detected in pools of Aedes vexans nipponii (n=1) and Aedes esoensis (n=3) collected in 2012 and 2013 near the demilitarized zone (DMZ), Republic of Korea (ROK). Phylogenetic analyses of the NS5, E gene and complete polyprotein coding sequence (CDS) showed that the novel virus fell within the Aedes-borne flaviviruses (ABFVs), with nucleotide identity ranging from 57.8-75.1 %, 46.1-74.2 % and 51.1-76.2 %, respectively. While the novel ABFV was distant from other flaviviruses within the group, it formed a clade with Ilomantsi virus (ILOV). Sequence alignments of the partial NS5 gene, full-length E gene and polyprotein CDS between the novel virus and ILOV showed approximately 76.2 % nucleotide identity and 90 % amino acid identity, respectively. The ABFV identified in Aedes mosquitoes from the ROK is a novel ABFV based on the sequence analyses and is designated as Panmunjeom flavivirus (PANFV).

The Molecular Specificity of the Human Antibody Response to Dengue Virus Infections.

PubMed

Gallichotte, Emily N; Baric, Ralph S; de Silva, Aravinda M

2018-01-01

Dengue viruses (DENV) are mosquito-borne positive sense RNA viruses in the family Flaviviridae. The four serotypes of DENV (DENV1, DENV2, DENV3, DENV4) are widely distributed and it is estimated over a third of the world's population is at risk of infection [4]. While the majority of infections are asymptomatic, DENV infection can cause a spectrum of disease, from mild flu-like symptoms, to the more severe DENV hemorrhagic fever and shock syndrome [24]. Over the past 20 years, there have been intense efforts to develop a tetravalent live-attenuated DENV vaccine [36]. The process of vaccine development has been largely empirical, because effective live attenuated vaccines have been developed for other flaviviruses like yellow fever and Japanese encephalitis viruses. However, recent results from phase III live attenuated DENV vaccine efficacy trials are mixed with evidence for efficacy in some populations but not others [20]. In light of unexpected results from DENV vaccine trials, in this chapter we will review recent discoveries about the human antibody response to natural DENV infection and discuss the relevance of this work to understanding vaccine performance.

Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses.

PubMed

Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong

2016-08-03

Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance.

Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer

ClinicalTrials.gov

2017-04-17

Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Aggressive NK-cell Leukemia; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV Infection; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Central Nervous System Lymphoma; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage I Small Lymphocytic Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Hodgkin Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Childhood Small Noncleaved Cell Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage III Childhood Small Noncleaved Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Small Lymphocytic Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Childhood Small Noncleaved Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

[Exposure to avian influenza virus and the infection status of virus among people breeding or butchering ducks in the suburb of Beijing].

PubMed

Ma, Chun-na; Yang, Peng; Zhang, Yi; Li, Hai-yue; Zhang, Li; Li, Li-li; Li, Chao; Yang, Yu-song; Chen, He; Zhang, Song-jian; Liu, Xiu-jun; Wang, Quan-yi

2012-04-01

To understand the exposure and the infection status of virus among people engaging in breeding or butchering ducks in the suburb of Beijing. People from six districts (Daxing, Fangshan, Huairou, Miyun, Shunyi, Tongzhou) who engaged in breeding or butchering ducks were studied and the status of infecting avian influenza virus was obtained by testing antibody level in serum. Information on demographic characteristics, status of regular exposure and exposure to sick or dead poultry were collected through a self-designed questionnaire. 1741 people were involved in this study in which 313 (18.0%) were workers in duck-breeding enterprise, 562 (32.3%) were workers in duck slaughterhouse, 261 (15.0%) farmers were in individual small-scale duck farms, 605 (34.7%) were farmers raising duck in backyard. Among farmers raising duck in backyard, the percentage of people whose ducks ever contacted with wild birds was higher than the other three groups (66.8%) (P<0.05). Among farmers who bred their ducks in the backyard (35.2%) and those abattoir workers (31.3%), the percentage of people who had contacted ducks but not been vaccinated with avian influenza vaccine was higher than the other two groups (P<0.05). Regarding the status on cleaning and disinfection among the studied farmers who had bred their ducks in the backyard, the percentage of people who had closer contact with ducks would clean the settings more than 4 times per month (8.8%) and disinfected those places more than 12 times per year (27.3%) but still lower than the other three groups (P<0.05). Among those farmers who bred ducks in the backyard, the percentage of people who had ever touched duck with their hands was high (34.4%) (P<0.05). Regarding exposure to sick or dead poultry, higher proportion was found among those who had ever closely contacted sick or dead poultry commercial duck raisers (36.1%) and individuals who raise large amount of ducks (36.0%). 70.8% of the individual duck raisers had never taken any protective measures when closely contacting the sick or dead poultry. Among 1741 samples, 0 were positive to avian influenza virus H5 and H7 subtypes. 12 were positive to H9 subtype (positive rate was 0.7%), in which 10 were farmers raising ducks in backyard (the positive rate of 1.7%). Differences between H9 subtype antibody positive rates difference in 4 population groups were statistically significant (χ2=13.699, P<0.05). Farmers who bred their ducks in the backyard had greater risk of contracting the avian influenza. Individual duckers who raise ducks in large scale and the farmers who bred their ducks in the backyard were in lack of protective measures when contacting the sick or dead poultry. Our findings suggested that some intervention measures should be taken to reduce the risk of avian influenza infection.

A Dense Poly(ethylene glycol) Coating Improves Penetration of Large Polymeric Nanoparticles within Brain Tissue

PubMed Central

Nance, Elizabeth A.; Woodworth, Graeme F.; Sailor, Kurt A.; Shih, Ting-Yu; Xu, Qingguo; Swaminathan, Ganesh; Xiang, Dennis; Eberhart, Charles; Hanes, Justin

2013-01-01

Prevailing opinion suggests that only substances up to 64 nm in diameter can move at appreciable rates through the brain extracellular space (ECS). This size range is large enough to allow diffusion of signaling molecules, nutrients, and metabolic waste products, but too small to allow efficient penetration of most particulate drug delivery systems and viruses carrying therapeutic genes, thereby limiting effectiveness of many potential therapies. We analyzed the movements of nanoparticles of various diameters and surface coatings within fresh human and rat brain tissue ex vivo and mouse brain in vivo. Nanoparticles as large as 114-nm in diameter diffused within the human and rat brain, but only if they were densely coated with poly(ethylene glycol) (PEG). Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm, and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles, spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible. PMID:22932224

Position sensitivity in large spectroscopic LaBr3:Ce crystals for Doppler broadening correction

NASA Astrophysics Data System (ADS)

Blasi, N.; Giaz, A.; Boiano, C.; Brambilla, S.; Camera, F.; Million, B.; Riboldi, S.

2016-12-01

The position sensitivity of a large LaBr3:Ce crystal was investigated with the aim of correcting for the Doppler broadening in nuclear physics experiments. The crystal was cylindrical, 3 in×3 in (7.62 cm x 7.62 cm) and with diffusive surfaces as typically used in nuclear physics basic research to measure medium or high energy gamma rays (0.5 MeV

Physical controls on directed virus assembly at nanoscale chemical templates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheung, C L; Chung, S; Chatterji, A

2006-05-10

Viruses are attractive building blocks for nanoscale heterostructures, but little is understood about the physical principles governing their directed assembly. In-situ force microscopy was used to investigate organization of Cowpea Mosaic Virus engineered to bind specifically and reversibly at nanoscale chemical templates with sub-30nm features. Morphological evolution and assembly kinetics were measured as virus flux and inter-viral potential were varied. The resulting morphologies were similar to those of atomic-scale epitaxial systems, but the underlying thermodynamics was analogous to that of colloidal systems in confined geometries. The 1D templates biased the location of initial cluster formation, introduced asymmetric sticking probabilities, andmore » drove 1D and 2D condensation at subcritical volume fractions. The growth kinetics followed a t{sup 1/2} law controlled by the slow diffusion of viruses. The lateral expansion of virus clusters that initially form on the 1D templates following introduction of polyethylene glycol (PEG) into the solution suggests a significant role for weak interaction.« less

Use of an Internal Positive Control in a Multiplex Reverse Transcription-PCR To Detect West Nile Virus RNA in Mosquito Pools

PubMed Central

Eisler, Diane L.; McNabb, Alan; Jorgensen, Danielle R.; Isaac-Renton, Judith L.

2004-01-01

We report on the use of West Nile virus Armored RNA as an internal positive control (IPC) for the extraction and reverse transcription-PCR (RT-PCR) of RNA extracted from field-collected mosquitoes and on a multiplex real-time Taqman RT-PCR to simultaneously detect the 3′ noncoding region of West Nile virus and the West Nile virus NS5-2 region comprising the IPC. Mosquito pools from the province of British Columbia, Canada (n = 635), were tested in duplicate and found to be negative for West Nile virus and positive for the IPC. Known West Nile virus-positive supernatants from mosquito pools from the provinces of Alberta and Manitoba were tested in duplicate and found to be positive for both regions of the West Nile virus genome. The mean cycle threshold (Ct) value for the IPC in batch extraction controls ± 2 standard deviations was found to be 36.43 ± 1.78 cycles. IPCs of 98.4% (624) of West Nile virus-negative pools fell within this range, indicating the reproducibility of RNA extraction and RT-PCR for pools varying in mosquito genus and number. A comparison of mosquito pool genera revealed no significant genus effect on the Ct value of the IPC. The incorporation of West Nile virus Armored RNA as an IPC allows monitoring of RNA extraction and RT-PCR and detection of false-negative results due to failures in these processes or to PCR inhibition, respectively. PMID:14766868

Substitutions in position 222 of haemagglutinin of pandemic influenza A (H1N1) 2009 viruses in Spain.

PubMed

Ledesma, Juan; Pozo, Francisco; Pérez Ruiz, Mercedes; Navarro, Jose María; Piñeiro, Luis; Montes, Milagros; Pérez Castro, Sonia; Suárez Fernández, Jonathan; García Costa, Juan; Fernández, Mirian; Galán, Juan Carlos; Cuevas, María Teresa; Casas, Inmaculada; Pérez Breña, Pilar

2011-05-01

A change of aspartic acid (D) to glycine (G) at position 222 in the haemagglutinin (HA) protein of pandemic influenza A (H1N1) 2009 viruses was described in Norway on November 2009 with considerable frequency in fatal and severe cases. This change was detected in other countries and was related only with severe disease. Other substitutions to glutamic acid (E) or asparagine (N) at position 222 were detected among pandemic viruses but it is unclear what implications might have in terms of severity. To analyse the appearance of amino acid substitutions at position 222 in the HA protein of circulating viruses in Spain and to determine their relationships with the disease symptoms observed. Pandemic influenza A (H1N1) 2009 viruses detected in respiratory samples of 273 severe and 533 non-severe cases from different Spanish regions were selected for sequencing of a partial segment of HA1 subunit and studied to monitor substitutions at position 222. D222G substitution was only detected in viruses from 14 severe cases (5.12%). D222E was found in viruses from 47 severe (17.21%) and from 52 non-severe cases (9.75%). D222N occurred in viruses from 3 additional severe cases (0.37%). Appearance of D222G and D222E substitution in HA of pandemic influenza A (H1N1) viruses circulating in Spain might be related with severe respiratory disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Non-local transport in turbulent MHD convection

NASA Technical Reports Server (NTRS)

Miesch, Mark; Brandenburg, Axel; Zweibel, Ellen; Toomre, Juri

1995-01-01

The nonlocal non-diffusive transport of passive scalars in turbulent magnetohydrodynamic (MHD) convection is investigated using transilient matrices. These matrices describe the probability that a tracer particle beginning at one position in a flow will be advected to another position after some time. A method for the calculation of these matrices from simulation data which involves following the trajectories of passive tracer particles and calculating their transport statistics, is presented. The method is applied to study the transport in several simulations of turbulent, rotating, three dimensional compressible, penetrative MDH convection. Transport coefficients and other diagnostics are used to quantify the transport, which is found to resemble advection more closely than diffusion. Some of the results are found to have direct relevance to other physical problems, such as the light element depletion in sun-type stars. The large kurtosis found for downward moving particles at the base of the convection zone implies several extreme events.

Broadband Respiratory Virus Surveillance

DTIC Science & Technology

2011-10-01

Simplex Virus (HSV) and 19 Enterovirus 7 positive as well as 11 HSV negative specimens as determined by the TAMC Department of Pathology’s current gold...negative, and 19 Enterovirus positive samples were to serve as negative controls as the RVS plate did not have primers to assay for HSV or Enterovirus . As...expected, all of these specimens ( Enterovirus , HSV positive and negative virus samples) tested negative on the RVS plate. This demonstrated 100

Prevalence of asymptomatic Zika virus infection: a systematic review.

PubMed

Haby, Michelle M; Pinart, Mariona; Elias, Vanessa; Reveiz, Ludovic

2018-06-01

To conduct a systematic review to estimate the prevalence of asymptomatic Zika virus infection in the general population and in specific population groups. We searched PubMed®, Embase® and LILACS online databases from inception to 26 January 2018. We included observational epidemiological studies where laboratory testing was used to confirm positive exposure of participants to Zika virus and in which Zika virus symptom status was also recorded. We excluded studies in which having symptoms of Zika virus was a criterion for inclusion. The main outcome assessed was percentage of all Zika virus-positive participants who were asymptomatic. We used a quality-effects approach and the double arcsine transformation for the meta-analysis. We assessed 753 studies for inclusion, of which 23 were included in the meta-analysis, totalling 11 305 Zika virus-positive participants. The high degree of heterogeneity in the studies ( I 2  = 99%) suggests that the pooled prevalence of asymptomatic Zika virus-positive participants was probably not a robust estimate. Analysis based on subgroups of the population (general population, returned travellers, blood donors, adults with Guillain-Barré syndrome, pregnant women and babies with microcephaly) was not able to explain the heterogeneity. Funnel and Doi plots showed major asymmetry, suggesting selection bias or true heterogeneity. Better-quality research is needed, using standardized methods, to determine the true prevalence of asymptomatic Zika virus and whether it varies between populations or over time.

The prognosis of MYC translocation positive diffuse large B-cell lymphoma depends on the second hit.

PubMed

Clipson, Alexandra; Barrans, Sharon; Zeng, Naiyan; Crouch, Simon; Grigoropoulos, Nicholas F; Liu, Hongxiang; Kocialkowski, Sylvia; Wang, Ming; Huang, Yuanxue; Worrillow, Lisa; Goodlad, John; Buxton, Jenny; Neat, Michael; Fields, Paul; Wilkins, Bridget; Grant, John W; Wright, Penny; Ei-Daly, Hesham; Follows, George A; Roman, Eve; Watkins, A James; Johnson, Peter W M; Jack, Andrew; Du, Ming-Qing

2015-07-01

A proportion of MYC translocation positive diffuse large B-cell lymphomas (DLBCL) harbour a BCL2 and/or BCL6 translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with MYC translocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolated MYC translocation. We investigated TP53 gene mutations along with BCL2 and BCL6 translocations in a total of 234 cases of DLBCL, including 81 with MYC translocation. TP53 mutations were investigated by PCR and sequencing, while BCL2 and BCL6 translocation was studied by interphase fluorescence in situ hybridization. The majority of MYC translocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. In MYC translocation positive DLBCL treated by R-CHOP ( n  = 67), TP53 mutation and BCL2, but not BCL6 translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolated MYC translocation, cases with MYC/TP53 double-hits had the worst overall survival, followed by those with MYC/BCL2 double-hits. In MYC translocation negative DLBCL treated by R-CHOP ( n  = 101), TP53 mutation, BCL2 and BCL6 translocation had no impact on patient survival. The prognosis of MYC translocation positive DLBCL critically depends on the second hit, with TP53 mutations and BCL2 translocation contributing to an adverse prognosis. It is pivotal to investigate both TP53 mutations and BCL2 translocations in MYC translocation positive DLBCL, and to distinguish double-hit DLBCLs from those with an isolated MYC translocation.

Lenalidomide And Rituximab as Maintenance Therapy in Treating Patients With B-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2015-11-25

Adult Non-Hodgkin Lymphoma; Adult Grade III Lymphomatoid Granulomatosis; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

Incidence of Enteric Viruses in Groundwater from Household Wells in Wisconsin

PubMed Central

Borchardt, Mark A.; Bertz, Phil D.; Spencer, Susan K.; Battigelli, David A.

2003-01-01

Recent studies on the contamination of groundwater with human enteric viruses have focused on public water systems, whereas little is known about the occurrence of viruses in private household wells. The objective of the present study was to estimate the incidence of viruses in Wisconsin household wells located near septage land application sites or in rural subdivisions served by septic systems. Fifty wells in seven hydrogeologic districts were sampled four times over a year, once each season. Reverse transcriptase PCR (RT-PCR), followed by Southern hybridization, was used to detect enteroviruses, rotavirus, hepatitis A virus (HAV), and Norwalk-like viruses (NLVs). In addition, cell culture was used to detect culturable enteroviruses. Companion water samples were collected for total coliforms, Escherichia coli, fecal enterococci, F-specific RNA coliphages, nitrate, and chloride analyses. Among the 50 wells, four (8%) were positive for viruses by RT-PCR. Three wells were positive for HAV, and the fourth well was positive for both rotavirus and NLV in one sample and an enterovirus in another sample. Contamination was transient, since none of the wells was virus positive for two sequential samples. Culturable enteroviruses were not detected in any of the wells. Water quality indicators were not statistically associated with virus occurrence, although some concordance was noted for chloride. The present study is the first in the United States to systematically monitor private household wells for virus contamination and, combined with data for public wells, provides further insight on the extent of groundwater contamination with human enteric viruses. PMID:12571044

Lymphocytic Arteritis in Epstein-Barr Virus Vulvar Ulceration (Lipschütz Disease): A Report of 7 Cases.

PubMed

Barrett, Mary M; Sangüeza, Martin; Werner, Betina; Kutzner, Heinz; Carlson, John A

2015-09-01

Epstein-Barr virus (EBV) infection can rarely present as painful genital ulcers, mostly in young female adolescents. Typically diagnosed by clinical findings, EBV vulvar ulceration (EBVVU) is rarely biopsied. Herein, the authors report the histopathology in 8 biopsies from 7 EBVVU patients, all serologically confirmed for acute (4/7) or reactivated-chronic (3/7) EBV infection. The 7 women all presented with 1 or more painful, punched-out vulvar ulcers. Only patients with acute EBV infection showed other clinical findings: fever and/or atypical lymphocytosis affected 75% (3/4); lymphadenopathy in 50%; and malaise/fatigue, dysuria and/or hepatomegaly in 25%. All reactivated-chronic EBVVU had a solitary ulcer, and 2 had history of a similar episode of vulvar ulceration (aphthosis). Histopathologically, lymphocytic arteritis was identified in 88% (7/8); a submucosal scar was found in the eighth specimen. Other histopathologies included venulitis (62%), endarteritis obliterans (38%), thrombosis (25%), neutrophilic sebaceous adenitis (25%), and mucosal lymphoid hyperplasia (12%). Dense angiocentric CD3 CD4 T-cell lymphocyte-predominant infiltrates were found, regionally or diffusely. In 2 specimens, neutrophils compromised half of the infiltrate. Minor components of CD8, CD20, and CD30 lymphocytes, CD123 plasmacytoid monocytes, CD68 macrophages, and plasma cells were present. Small-vessel endothelium and smooth muscle adjacent to the ulcers faintly expressed cytoplasmic EBV latent membrane protein-1 (LMP1). In situ hybridization for early EBV mRNA (EBER) identified rare solitary or scattered clustered positive lymphocytes in 38%. Polymerase chain reaction for EBV DNA was positive in one EBER positive biopsy. EBV infection has been documented in muscular vessel vasculitis. Based on the aforementioned, EBVVU appears to be the consequence of localized lymphocytic arteritis.

Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1

PubMed Central

Resti, Massimo; Azzari, Chiara; Mannelli, Francesco; Moriondo, Maria; Novembre, Elio; de Martino, Maurizio; Vierucci, Alberto

1998-01-01

Objective: To determine the risk factors for and timing of vertical transmission of hepatitis C virus in women who are not infected with HIV-1. Design: Follow up for a median of 28 (range 24-38) months of babies born to women with antibodies to hepatitis C virus but not HIV-1. Subjects: 442 mothers and babies, of whom 403 completed the study. Main outcome measures: Presence of antibodies to hepatitis C virus and viral RNA and alanine aminotransferase activity in babies. Presence of viral RNA, method of infection with hepatitis C, method of delivery, and type of infant feeding in mothers. Results: 13 of the 403 children had acquired hepatitis C virus infection at the end of follow up. All these children were born to women positive for hepatitis C virus RNA; none of the 128 RNA negative mothers passed on the infection (difference 5%, 95% confidence interval 2% to 7%). 6 children had viral RNA immediately after birth. 111 women had used intravenous drugs and 20 had received blood transfusions. 11 of the infected children were born to these women compared with 2 to the 144 with no known risk factor (difference 7%, 2% to 12%). Conclusions: This study suggests that in women not infected with HIV only those with hepatitis C virus RNA are at risk of infecting their babies. Transmission does seem to occur in utero, and the rate of transmission is higher in women who have had blood transfusions or used intravenous drugs than in women with no known risk factor for infection. Key messages Little information exists on vertical transmission of hepatitis C virus in women not infected with HIV This study in a large unselected population of infants born to HIV-1 negative mothers suggests that intravenous drug use itself is an important risk factor for transmission of hepatitis C virus Maternal post-transfusional hepatitis is also an important risk factor for infection of infants Viral genotype, maternal viraemia, type of delivery (vaginal delivery or caesarean section) and breast feeding do not seem to be risk factors In utero transmission of hepatitis C virus has been suggested by RNA positivity on day of birth in some infected children PMID:9703524

Viral hemorrhagic fevers of animals caused by positive-stranded RNA viruses

USDA-ARS?s Scientific Manuscript database

Here we outline serious diseases of wildlife, food and fiber animals, and non-human primates that cause damaging economic effects on producers all over the world. While some zoonotic viruses that occasionally cause serious disease and death in humans are mentioned, the positive sense RNA viruses ge...

No serological evidence for Zika virus infection and low specificity for anti-Zika virus ELISA in malaria positive individuals among pregnant women from Madagascar in 2010.

PubMed

Schwarz, Norbert Georg; Mertens, Eva; Winter, Doris; Maiga-Ascofaré, Oumou; Dekker, Denise; Jansen, Stephanie; Tappe, Dennis; Randriamampionona, Njary; May, Jürgen; Rakotozandrindrainy, Raphael; Schmidt-Chanasit, Jonas

2017-01-01

It was previously reported that a malaria infection may interfere with the specificity of a commercial ELISA test against Zika virus (ZIKV). We analyzed 1,216 plasma samples from healthy, pregnant women collected in two sites in Madagascar in 2010 for ZIKV antibodies using a commercial ELISA and for Plasmodium infection by PCR. This screen revealed six putative ZIKV-positive samples by ELISA. These results could not be confirmed by indirect immunofluorescence assays or virus neutralization tests. Four of these six samples were also positive for P. falciparum. We noted that the frequency of malaria positivity was higher in ZIKV-ELISA positive samples (50% and 100% in the two study sites) than ZIKV-negative samples (17% and 10%, respectively), suggesting that malaria may have led to false ZIKV-ELISA positives.

An attempt to eradicate Herpesvirus simiae from a rhesus monkey breeding colony.

PubMed

Sauber, J J; Fanton, J W; Harvey, R C; Golden, J G

1992-10-01

In the fall of 1987 an attempt to establish a Herpesvirus simiae (B-virus)-negative rhesus monkey (Macaca mulatta) breeding colony was initiated at the Armstrong Laboratory. A serologic testing program was used to identify all monkeys into groups that were either positive or negative to B-virus based on serologic tests. Segregation of the groups allowed the creation of breeding harems that were exclusively seropositive or -negative to B-virus. Animals that were serologically positive were kept in breeding to maintain infant production levels not unlike those previous to segregation. Decreasing numbers of animals converted to a positive status during the first three serum tests for B-virus in the program. During 1990, an increase in the number of monkeys converting to positive status and the discovery of an indeterminate status demonstrated that latency of B-virus in the rhesus may have the potential to defeat an eradication attempt not conscientiously pursued.

Large lateral photovoltaic effect with ultrafast relaxation time in SnSe/Si junction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xianjie; Zhao, Xiaofeng; Hu, Chang

In this paper, we report a large lateral photovoltaic effect (LPE) with ultrafast relaxation time in SnSe/p-Si junctions. The LPE shows a linear dependence on the position of the laser spot, and the position sensitivity is as high as 250 mV mm{sup −1}. The optical response time and the relaxation time of the LPE are about 100 ns and 2 μs, respectively. The current-voltage curve on the surface of the SnSe film indicates the formation of an inversion layer at the SnSe/p-Si interface. Our results clearly suggest that most of the excited-electrons diffuse laterally in the inversion layer at the SnSe/p-Si interface, whichmore » results in a large LPE with ultrafast relaxation time. The high positional sensitivity and ultrafast relaxation time of the LPE make the SnSe/p-Si junction a promising candidate for a wide range of optoelectronic applications.« less

[Detection of herpes virus and human enterovirus in pathology samples using low-density arrays].

PubMed

Del Carmen Martínez, Sofía; Gervás Ríos, Ruth; Franco Rodríguez, Yoana; González Velasco, Cristina; Cruz Sánchez, Miguel Ángel; Abad Hernández, María Del Mar

Despite the frequency of infections with herpesviridae family, only eight subtypes affect humans (Herpex Simplex Virus types 1 and 2, Varicella Zoster Virus, Epstein-Barr Virus, Citomegalovirus and Human Herpes Virus types 6, 7 and 8). Amongst enteroviruses infections, the most important are Poliovirus, Coxackievirus and Echovirus. Symptoms can vary from mild to severe and early diagnosis is of upmost importance. Nowadays, low-density arrays can detect different types of viruses in a single assay using DNA extracted from biological samples. We analyzed 70 samples of formalin-fixed and paraffin-embedded tissue, searching for viruses (HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, HHV-7 y HHV-8, Poliovirus, Echovirus and Coxsackievirus) using the kit CLART ® ENTHERPEX. Out of the total of 70 samples, 29 were positive for viral infection (41.43%), and only 4 of them showed cytopathic effect (100% correlation between histology and the test). 47.6% of GVHD samples were positive for virus; 68.75% of IBD analyzed showed positivity for viral infection; in colitis with ulcers (neither GVHD nor IBD), the test was positive in 50% of the samples and was also positive in 50% of ischemic lesions. The high sensitivity of the technique makes it a useful tool for the pathologist in addition to conventional histology-based diagnosis, as a viral infection may affect treatment. Copyright © 2016 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

Understanding Glocal Learning Spaces. An Empirical Study of Languaging and Transmigrant Positions in the Virtual Classroom

ERIC Educational Resources Information Center

Messina Dahlberg, Giulia; Bagga-Gupta, Sangeeta

2014-01-01

The use of digital tools like computers and tablets in institutional learning arenas give rise to forms of flexibility where time and space boundaries become diffuse. Online learning sites are understood as being crucial today, especially in large parts of the Global North, where anyone anywhere potentially can become a student and have access to…

Development of an indirect ELISA for detection of antibody to wobbly possum disease virus in archival sera of Australian brushtail possums (Trichosurus vulpecula) in New Zealand.

PubMed

Giles, J C; Johnson, W; Jones, G; Heuer, C; Dunowska, M

2018-07-01

To develop an indirect ELISA based on recombinant nucleocapsid (rN) protein of wobbly possum disease (WPD) virus for investigation of the presence of WPD virus in Australian brushtail possums (Trichosurus vulpecula) in New Zealand. Pre- and post-infection sera (n=15 and 16, respectively) obtained from a previous experimental challenge study were used for ELISA development. Sera were characterised as positive or negative for antibody to WPD virus based on western-blot using WPD virus rN protein as antigen. An additional 215 archival serum samples, collected between 2000-2016 from five different regions of New Zealand, were also tested using the ELISA. Bayesian modelling of corrected optical density at 450 nm (OD 450 ) results from the ELISA was used to obtain estimates of receiver operating characteristic (ROC) curves to establish cut-off values for the ELISA, and to estimate the prevalence of antibody to WPD virus. Western blot analysis showed 5/14 (36%) pre-infection sera and 11/11 (100%) post-infection sera from experimentally infected possums were positive for antibodies to WPD virus. Bayesian estimates of the ROC curves established cut-off values of OD 450 ≥0.41 for samples positive, and OD 450 <0.28 for samples negative for antibody to WPD virus, for sera diluted 1:100 for the ELISA. Based on the model, the estimated proportion of samples with antibodies to WPD virus was 0.30 (95% probability interval=0.196-0.418). Of the 230 archival serum samples tested using the ELISA, 48 (20.9%) were positive for antibody to WPD virus, 155 (67.4%) were negative and 27 (11.7%) equivocal, using the established cut-off values. The proportion of samples positive for WPD virus antibody differed between geographical regions (p<0.001). The results suggested that WPD virus or a related virus has circulated among possums in New Zealand with differences in the proportion of antibody-positive samples from different geographical regions. Antibodies to WPD virus did not seem to protect possums from disease following experimental infection, as one third of possums from the previous challenge study showed evidence of pre-existing antibody at the time of challenge. These results provide further support for existence of different pathotypes of WPD virus, but the exact determinants of protection against WPD and epidemiology of infection in various regions of New Zealand remain to be established. Availability of the indirect ELISA for detection of WPD virus antibody will facilitate prospective epidemiological investigation of WPD virus circulation in wild possum populations in New Zealand.

Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1-6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance.

PubMed

Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof

2015-09-16

Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1-6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%-0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be genotype-specific or geographically tailored.

Hepatitis B and C virus co-infections in human immunodeficiency virus positive North Indian patients

PubMed Central

Gupta, Swati; Singh, Sarman

2006-01-01

AIM: To determine the prevalence of hepatitis B and C virus infections in human immunodeficiency virus (HIV) -positive patients at a tertiary care hospital in New Delhi, India. METHODS: Serum samples from 451 HIV positive patients were analyzed for HBsAg and HCV antibodies during three years (Jan 2003-Dec 2005). The control group comprised of apparently healthy bone-marrow and renal donors. RESULTS: The study population comprised essentially of heterosexually transmitted HIV infection. The prevalence rate of HBsAg in this population was 5.3% as compared to 1.4% in apparently healthy donors (P < 0.001). Though prevalence of HCV co-infection (2.43%) was lower than HBV in this group of HIV positive patients, the prevalence was significantly higher (P < 0.05) than controls (0.7%). Triple infection of HIV, HBV and HCV was not detected in any patient. CONCLUSION: Our study shows a significantly high prevalence of hepatitis virus infections in HIV infected patients. Hepatitis viruses in HIV may lead to faster progression to liver cirrhosis and a higher risk of antiretroviral therapy induced hepatotoxicity. Therefore, it would be advisable to detect hepatitis virus co-infections in these patients at the earliest. PMID:17106941