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Sample records for active cytomegalovirus infections

  1. Cytomegalovirus infection.

    PubMed

    Climent, C; Vélez, R; Capriles, J A

    1992-01-01

    Post-transfusion CMV infection most frequently results in asymptomatic seroconversion. Among immunocompetent patients only seronegative pregnant women require such products because of the risk of fetal CMV infection. In selected groups of immunocompromised patients, significant disease can occur. It is desirable to provide blood and blood components with reduced CMV risk to the following patients: seronegative infants weighting less than 1200 g at birth, seronegative bone marrow transplant patients who receive marrow from seronegative donors and seronegative renal transplant patients receiving kidneys from seronegative donors. Heart and liver transplantation seronegative patients may receive seronegative blood if the donor is seronegative. CMV--seronegative HIV infected cases may also be transfused with CMV--seronegative blood. PMID:1323967

  2. Cytomegalovirus Infection in Inflammatory Bowel Disease Is Not Associated with Worsening of Intestinal Inflammatory Activity

    PubMed Central

    do Carmo, Alexandre Medeiros; Santos, Fabiana Maria; Ortiz-Agostinho, Carmen Lucia; Nishitokukado, Iêda; Frota, Cintia S.; Gomes, Flavia Ubeda; de Arruda Leite, André Zonetti; Pannuti, Claudio Sérgio; Boas, Lucy Santos Vilas; Teixeira, Magaly Gemio; Sipahi, Aytan Miranda

    2014-01-01

    Background Cytomegalovirus is highly prevalent virus and usually occurs in immunocompromised patients. The pathophysiology and treatment of inflammatory bowel disease often induce a state of immunosuppression. Because this, there are still doubts and controversies about the relationship between inflammatory bowel disease and cytomegalovirus. Aim Evaluate the frequency of cytomegalovirus in patients with inflammatory bowel disease and identify correlations. Methods Patients with inflammatory bowel disease underwent an interview, review of records and collection of blood and fecal samples. The search for cytomegalovirus was performed by IgG and IgM blood serology, by real-time PCR in the blood and by qualitative PCR in feces. Results were correlated with red blood cell levels, C-reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin levels for each patient. Results Among the 400 eligible patients, 249 had Crohn's disease, and 151 had ulcerative colitis. In the group of Crohn's disease, 67 of the patients had moderate or severe disease, but 126 patients presented with active disease, based on the evaluation of the fecal calprotectin. In patients with ulcerative colitis, only 21 patients had moderate disease, but 76 patients presented with active disease, based on the evaluation of the fecal calprotectin. A large majority of patients had positive CMV IgG. Overall, 10 patients had positive CMV IgM, and 9 patients had a positive qualitative detection of CMV DNA by PCR in the feces. All 400 patients returned negative results after the quantitative detection of CMV DNA in blood by real-time PCR. Analyzing the 19 patients with active infections, we only found that such an association occurred with the use of combined therapy (anti-TNF-alpha + azathioprine) Conclusion The findings show that latent cytomegalovirus infections are frequent and active cytomegalovirus infection is rare. We did not find any association between an active infection of CMV

  3. Cytomegalovirus infection in transplant recipients

    PubMed Central

    Azevedo*, Luiz Sergio; Pierrotti, Lígia Camera; Abdala, Edson; Costa, Silvia Figueiredo; Strabelli, Tânia Mara Varejão; Campos, Silvia Vidal; Ramos, Jéssica Fernandes; Latif, Acram Zahredine Abdul; Litvinov, Nadia; Maluf, Natalya Zaidan; Filho, Helio Hehl Caiaffa; Pannuti, Claudio Sergio; Lopes, Marta Heloisa; dos Santos, Vera Aparecida; da Cruz Gouveia Linardi, Camila; Yasuda, Maria Aparecida Shikanai; de Sousa Marques, Heloisa Helena

    2015-01-01

    Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia. PMID:26222822

  4. Cytomegalovirus infection in transplant recipients.

    PubMed

    Azevedo, Luiz Sergio; Pierrotti, Lígia Camera; Abdala, Edson; Costa, Silvia Figueiredo; Strabelli, Tânia Mara Varejão; Campos, Silvia Vidal; Ramos, Jéssica Fernandes; Latif, Acram Zahredine Abdul; Litvinov, Nadia; Maluf, Natalya Zaidan; Caiaffa Filho, Helio Hehl; Pannuti, Claudio Sergio; Lopes, Marta Heloisa; Santos, Vera Aparecida dos; Linardi, Camila da Cruz Gouveia; Yasuda, Maria Aparecida Shikanai; Marques, Heloisa Helena de Sousa

    2015-07-01

    Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia. PMID:26222822

  5. Cytomegalovirus as nosocomial infection.

    PubMed

    Román González, J; Colón, M; Ramírez-Ronda, C H

    1991-08-01

    Nosocomial infections with cytomegalovirus are an area of great concern and controversy within the medical community. With the advent of organ transplantation there have been an increased number of susceptible individuals. In the past most cases were confined to newborn nurseries and the neonatal intensive care unit. It is of great interest that recent evidence suggests that health care providers are at no greater risk of acquiring CMV infection inside the hospital setting when compared to a representative control group within the same community. This paper will review some of the literature that deals with the nosocomial transmission of CMV. We will try to emphasize transmission, diagnosis, prevention, and treatment of CMV infection. PMID:1667848

  6. Cytomegalovirus Infection of the Rat Developing Brain In Utero Prominently Targets Immune Cells and Promotes Early Microglial Activation

    PubMed Central

    Cloarec, Robin; Bauer, Sylvian; Luche, Hervé; Buhler, Emmanuelle; Pallesi-Pocachard, Emilie; Salmi, Manal; Courtens, Sandra; Massacrier, Annick; Grenot, Pierre; Teissier, Natacha; Watrin, Françoise; Schaller, Fabienne; Adle-Biassette, Homa; Gressens, Pierre; Malissen, Marie; Stamminger, Thomas; Streblow, Daniel N.; Bruneau, Nadine; Szepetowski, Pierre

    2016-01-01

    Background Congenital cytomegalovirus infections are a leading cause of neurodevelopmental disorders in human and represent a major health care and socio-economical burden. In contrast with this medical importance, the pathophysiological events remain poorly known. Murine models of brain cytomegalovirus infection, mostly neonatal, have brought recent insights into the possible pathogenesis, with convergent evidence for the alteration and possible involvement of brain immune cells. Objectives and Methods In order to confirm and expand those findings, particularly concerning the early developmental stages following infection of the fetal brain, we have created a model of in utero cytomegalovirus infection in the developing rat brain. Rat cytomegalovirus was injected intraventricularly at embryonic day 15 (E15) and the brains analyzed at various stages until the first postnatal day, using a combination of gene expression analysis, immunohistochemistry and multicolor flow cytometry experiments. Results Rat cytomegalovirus infection was increasingly seen in various brain areas including the choroid plexi and the ventricular and subventricular areas and was prominently detected in CD45low/int, CD11b+ microglial cells, in CD45high, CD11b+ cells of the myeloid lineage including macrophages, and in CD45+, CD11b– lymphocytes and non-B non-T cells. In parallel, rat cytomegalovirus infection of the developing rat brain rapidly triggered a cascade of pathophysiological events comprising: chemokines upregulation, including CCL2-4, 7 and 12; infiltration by peripheral cells including B-cells and monocytes at E17 and P1, and T-cells at P1; and microglia activation at E17 and P1. Conclusion In line with previous findings in neonatal murine models and in human specimen, our study further suggests that neuroimmune alterations might play critical roles in the early stages following cytomegalovirus infection of the brain in utero. Further studies are now needed to determine which

  7. PPARγ Is Activated during Congenital Cytomegalovirus Infection and Inhibits Neuronogenesis from Human Neural Stem Cells

    PubMed Central

    Rolland, Maude; Li, Xiaojun; Perez-Berezo, Teresa; Rauwel, Benjamin; Benchoua, Alexandra; Bessières, Bettina; Aziza, Jacqueline; Cenac, Nicolas; Luo, Minhua; Casper, Charlotte; Peschanski, Marc; Gonzalez-Dunia, Daniel; Leruez-Ville, Marianne; Davrinche, Christian; Chavanas, Stéphane

    2016-01-01

    Congenital infection by human cytomegalovirus (HCMV) is a leading cause of permanent sequelae of the central nervous system, including sensorineural deafness, cerebral palsies or devastating neurodevelopmental abnormalities (0.1% of all births). To gain insight on the impact of HCMV on neuronal development, we used both neural stem cells from human embryonic stem cells (NSC) and brain sections from infected fetuses and investigated the outcomes of infection on Peroxisome Proliferator-Activated Receptor gamma (PPARγ), a transcription factor critical in the developing brain. We observed that HCMV infection dramatically impaired the rate of neuronogenesis and strongly increased PPARγ levels and activity. Consistent with these findings, levels of 9-hydroxyoctadecadienoic acid (9-HODE), a known PPARγ agonist, were significantly increased in infected NSCs. Likewise, exposure of uninfected NSCs to 9-HODE recapitulated the effect of infection on PPARγ activity. It also increased the rate of cells expressing the IE antigen in HCMV-infected NSCs. Further, we demonstrated that (1) pharmacological activation of ectopically expressed PPARγ was sufficient to induce impaired neuronogenesis of uninfected NSCs, (2) treatment of uninfected NSCs with 9-HODE impaired NSC differentiation and (3) treatment of HCMV-infected NSCs with the PPARγ inhibitor T0070907 restored a normal rate of differentiation. The role of PPARγ in the disease phenotype was strongly supported by the immunodetection of nuclear PPARγ in brain germinative zones of congenitally infected fetuses (N = 20), but not in control samples. Altogether, our findings reveal a key role for PPARγ in neurogenesis and in the pathophysiology of HCMV congenital infection. They also pave the way to the identification of PPARγ gene targets in the infected brain. PMID:27078877

  8. Cytomegalovirus infection: an Indian perspective.

    PubMed

    Chakravarti, A; Kashyap, B; Matlani, M

    2009-01-01

    Human cytomegalovirus (CMV) poses an important public health problem as it may cause serious morbidity and mortality in congenitally infected newborns and immunocompromised patients, most notably transplant recipients and HIV-infected persons. It is probably one of the most common infections known to humans and is characterized by a self-limiting infection in healthy individuals. CMV infection is the single most frequent cause of infectious complications in the early period following kidney transplantation Post-transfusion cytomegalovirus infection is of concern in the immunocompetent as well as in certain categories of immunocompromised individuals such as neonates, pregnant women, recipients of bone marrow and other organ transplants and individuals with immunodeficiency disorders. The emergence of AIDS in India has necessitated the establishment of reliable tests for diagnosis of cytomegalovirus infection as a damaged immune system permits cytomegalovirus reactivation. The magnitude of this problem in India and the various diagnostic modalities used have not been adequately investigated and, hence, CMV infection is still a major health problem warranting strong preventive measures. The ultimate goal of the prevention program is to develop a vaccine that can be administered to seronegative women of childbearing age to prevent primary infection during pregnancy. PMID:19172051

  9. Cytomegalovirus Infection in Ireland

    PubMed Central

    Hassan, Jaythoon; O’Neill, Derek; Honari, Bahman; De Gascun, Cillian; Connell, Jeff; Keogan, Mary; Hickey, David

    2016-01-01

    Abstract Cytomegalovirus (CMV) infections occur worldwide and primary infection usually occurs in early childhood and is often asymptomatic whereas primary infection in adults may result in symptomatic illness. CMV establishes a chronic latent infection with intermittent periods of reactivation. Primary infection or reactivation associate with increased mortality and morbidity in those who are immunocompromised. Transplacental transmission may result in significant birth defects or long-term sensorineural hearing loss. We performed a study to determine the CMV seroprevalence and the association between HLA Class I alleles and frequency of CMV infection in Ireland. The presence of CMV IgG, a marker of previous CMV infection, was determined for a cohort of 1849 HLA typed solid organ transplant donors between 1990 and 2013. The presence of CMV IgG was correlated with HLA type. The CMV seroprevalence in solid organ transplant donors was 33.4% (range 22–48% per annum) over the time period 1990 to 2013. Multivariate logistic regression analysis showed that both age and HLA alleles were associated with CMV seropositivity. A significant and positive relationship between age and CMV seropositivity was observed (OR = 1.013, P < 0.001, CI [1.007, 1.019]). Chi-square analysis revealed that the female gender was independently associated with CMV seropositivity (P < 0.01). Seroprevalence in women of reproductive age (20–39 years) was significantly higher than men of the same age (37% vs 26%, P < 0.01). The frequencies of HLA-A1, HLA-A2, and HLA-A3 in our cohort were 40.8%, 48.8%, and 25.9%, respectively. Logistic regression analysis showed that the presence of HLA-A1 but not HLA-A2 or HLA-A3 was independently associated with CMV seronegativity (P < 0.01). Interestingly, individuals who co-expressed HLA-A2 and HLA-A3 alleles were significantly more likely to be CMV seropositive (P < 0.02). The frequencies of HLA-B5, HLA-B7, and HLA-B8 in our cohort

  10. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

    PubMed

    Cousins, Scott W; Espinosa-Heidmann, Diego G; Miller, Daniel M; Pereira-Simon, Simone; Hernandez, Eleut P; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  11. Macrophage Activation Associated with Chronic Murine Cytomegalovirus Infection Results in More Severe Experimental Choroidal Neovascularization

    PubMed Central

    Cousins, Scott W.; Espinosa-Heidmann, Diego G.; Miller, Daniel M.; Pereira-Simon, Simone; Hernandez, Eleut P.; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D.

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  12. Latent cytomegalovirus infection exacerbates experimental pulmonary fibrosis by activating TGF-β1.

    PubMed

    Li, Yonghuai; Gao, Jian; Wang, Guoliang; Fei, Guanghe

    2016-08-01

    The aim of the present study was to investigate the hypotheses that cytomegalovirus (CMV) may trigger idiopathic pulmonary fibrosis (IPF) in a susceptible host and/or that the presence of CMV may alter IPF in response to a well-defined trigger of pulmonary fibrosis. A mouse model of murine CMV (MCMV) infection was established, and the mice were divided into a control group, bleomycin group and an MCMV+bleomycin group. Changes in the weights of the mice were determined in the three groups. Pulmonary fibrosis was detected using a histopathological method. The activity of transforming growth factor (TGF)‑β1 was measured, and the levels of E‑cadherin, Vimentin and phosphorylated (phospho)‑small mothers against decapentaplegic (SMAD)2 were determined using western blot analysis. MCMV was found to invade the lungs, however, it did not cause pulmonary fibrosis. The progression of fibrosis in the mice treated with MCMV+bleomycin was more rapid, compared with that in the control mice. The protein levels of Vimentin and phospho-SMAD2 were upregulated, whereas the level of E‑cadherin was downregulated in the MCMV+bleomycin group,. The results suggested that latent MCMV infection aggravated pulmonary fibrosis in the mouse model, possibly through the activation of TGF-β1. PMID:27279470

  13. Evolutive leukoencephalopathy in congenital cytomegalovirus infection.

    PubMed

    Krakar, Goran; Đaković, Ivana; Delin, Sanja; Bošnjak, Vlatka Mejaški

    2015-01-01

    Congenital cytomegalovirus infection is the most common infectious cause of congenital brain injury. Type and severity of congenital cytomegalovirus infection-related brain abnormalities depend on the developmental stage of the central nervous system at the time of fetal infection. The aim of this study was to follow the course of leukoencephalopathy in a patient with congenital cytomegalovirus infection. We describe brain magnetic resonance imaging (MRI) findings of a boy with symptomatic congenital cytomegalovirus infection performed at the age of 3 weeks, 13 months, and 4 and 7 years. Neonatal brain MRI showed most of characteristic findings in congenital cytomegalovirus infection with most prominent white matter abnormalities and cortical dysplasia. MRI follow-up images showed that cortical dysgenesis remained unchanged and static, whereas white matter abnormalities evolved over the years. We propose that leukoencephalopathy in congenital cytomegalovirus infection is not only nonprogressive or static but even evolutive and suggests both underlying disruption and delay of myelination. PMID:24453153

  14. Late cytomegalovirus infection after hematopoietic stem cell transplantation: case reports

    PubMed Central

    Pinheiro, Sâmara Grapiuna; de Matos, Sócrates Bezerra; Botura, Mônica Borges; Meyer, Roberto; Lima, Fernanda Washington de Mendonça

    2013-01-01

    Cytomegalovirus is related to high rates of morbidity and mortality after hematopoietic stem cell transplantation. This report highlights the importance of adequate monitoring and management of this infection. We report on two cases of patients with late subclinical cytomegalovirus infection. These patients were monitored for antigenemia by indirect immunofluorescence assay. Active cytomegalovirus infection is most common in the first three months after transplantation however the cases reported herein show the importance of monitoring for active infection after Day +100 post-transplantation. Early detection of active infection enables quick preemptive therapy. In conclusion, we emphasize that patients with risk factors for developing severe or late cytomegalovirus disease should be monitored for more than 100 post-transplant days as late active infection is a reality. PMID:24478611

  15. Acute cytomegalovirus (CMV) infection

    MedlinePlus

    ... by: Blood transfusions Organ transplants Respiratory droplets Saliva Sexual contact Urine Most people come into contact with ... with another person. You should avoid kissing and sexual contact with an infected person. The virus may ...

  16. Quantitative measurement of cytomegalovirus-specific IgG and IgM antibodies in relation to cytomegalovirus antigenaemia and disease activity in kidney recipients with an active cytomegalovirus infection.

    PubMed Central

    Van der Giessen, M; van den Berg, A P; van der Bij, W; Postma, S; van Son, W J; The, T H

    1990-01-01

    In a longitudinal investigation 103 kidney recipients were studied with respect to the development of cytomegalovirus (CMV) specific antibodies of the IgG and IgM class, in relation to the detection of CMV antigenaemia (immediate early antigen, IEA), in weekly obtained blood samples during the first 3 months after transplantation. In 15 out of 49 (31%) seronegative patients a primary infection occurred, which was characterized by a quick rise in IgM antibody followed by a slower production of IgG antibody, high maximum numbers of IEA+ cells, and a CMV syndrome in 11 patients. In 35 out of 54 (65%) seropositive patients a secondary infection occurred. After a post-operative fall in the IgG antibody, which was also found in patients without an active infection and which was accompanied by a similar drop in serum albumin and IgG, a second dip in IgG antibody was found 6 days before the first IEA+ leucocyte appeared in the blood. This was followed by a significant increase, indicative of an active immune response in consequence of the infection, 18 days later. In 31 of these 35 patients an IgM response was found. This could be ascribed to the presence of rheumatoid factor activity in 20 of them. Eight patients who showed a transient rise in IgG antibody between the two dips could be distinguished from the remaining ones by a lower maximum number of IEA+ cells and less severe disease symptoms. The described results suggest that (i) an adequate humoral immune system may prevent symptomatic CMV disease in secondary infections; and (ii) CMV-specific antibodies may be removed from the circulation by antigens present in infected tissues before CMV antigenaemia becomes detectable. PMID:2157567

  17. Interleukin-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against Human Cytomegalovirus-Infected Macrophages

    PubMed Central

    Wu, Zeguang; Frascaroli, Giada; Bayer, Carina; Schmal, Tatjana

    2015-01-01

    ABSTRACT Control of human cytomegalovirus (HCMV) requires a continuous immune surveillance, thus HCMV is the most important viral pathogen in severely immunocompromised individuals. Both innate and adaptive immunity contribute to the control of HCMV. Here, we report that peripheral blood natural killer cells (PBNKs) from HCMV-seropositive donors showed an enhanced activity toward HCMV-infected autologous macrophages. However, this enhanced response was abolished when purified NK cells were applied as effectors. We demonstrate that this enhanced PBNK activity was dependent on the interleukin-2 (IL-2) secretion of CD4+ T cells when reexposed to the virus. Purified T cells enhanced the activity of purified NK cells in response to HCMV-infected macrophages. This effect could be suppressed by IL-2 blocking. Our findings not only extend the knowledge on the immune surveillance in HCMV—namely, that NK cell-mediated innate immunity can be enhanced by a preexisting T cell antiviral immunity—but also indicate a potential clinical implication for patients at risk for severe HCMV manifestations due to immunosuppressive drugs, which mainly suppress IL-2 production and T cell responsiveness. IMPORTANCE Human cytomegalovirus (HCMV) is never cleared by the host after primary infection but instead establishes a lifelong latent infection with possible reactivations when the host′s immunity becomes suppressed. Both innate immunity and adaptive immunity are important for the control of viral infections. Natural killer (NK) cells are main innate effectors providing a rapid response to virus-infected cells. Virus-specific T cells are the main adaptive effectors that are critical for the control of the latent infection and limitation of reinfection. In this study, we found that IL-2 secreted by adaptive CD4+ T cells after reexposure to HCMV enhances the activity of NK cells in response to HCMV-infected target cells. This is the first direct evidence that the adaptive T cells can

  18. Congenital Cytomegalovirus Infection: Audiologic Outcome

    PubMed Central

    Fowler, Karen B.

    2013-01-01

    The association between congenital cytomegalovirus (CMV) infection and sensorineural hearing loss (SNHL) was first described almost 50 years ago. Studies over the intervening decades have further described the relationship between congenital CMV infection and SNHL in children. However, congenital CMV infection remains a leading cause of SNHL in children in the United States and the world today. As more CMV infections are identified, it is important to recognize that infants who are born to seroimmune mothers are not completely protected from SNHL, although their hearing loss is often milder than that seen in CMV-infected infants following primary maternal infections. Late-onset and progressive hearing losses occur following congenital CMV infection, and CMV-infected infants should be evaluated regularly to provide for early detection of hearing loss and appropriate intervention. Fluctuating hearing loss that is not explained by concurrent middle ear infections is another characteristic of CMV-related hearing loss in children. Challenges still remain in predicting which children with congenital CMV infection will develop hearing loss and, among those who do develop loss, whether or not the loss will continue to deteriorate. PMID:24257423

  19. EFFECTS OF IMMUNOSUPPRESSION WITH CYCLOPHOSPHAMIDE ON ACUTE MURINE CYTOMEGALOVIRUS INFECTION AND VIRUS-AUGMENTED NATURAL KILLER CELL ACTIVITY

    EPA Science Inventory

    The effects of cyclophosphamide (CY) treatment on acute murine cytomegalovirus (MCMV) infection were studied to explore the potential usefulness of MCMV as a means of detecting immune dysfunction and to identify host defense mechanisms important for protection against MCMV.

  20. Activity of trifluorothymidine against cytomegalovirus.

    PubMed Central

    Wingard, J R; Stuart, R K; Saral, R; Burns, W H

    1981-01-01

    Trifluorothymidine (TFT) was tested for antiviral activity against mouse cytomegalovirus (MCMV) and human cytomegalovirus (HCMV) in one-step replication assays. The TFT concentration required to reduce virus yield by 50% (ID50) was 0.22 microM for MCMV and 0.012 microM for HCMV. The antiviral activity of TFT against MCMV was reversed by addition of equimolar thymidine, and no antiviral activity was demonstrable in a host cell line lacking thymidine kinase. Thus, TFT's anti-MCMV activity is dependent on a host cell TK since this herpesvirus lacks thymidine kinase. A continuous subcutaneous infusion of TFT achieving a serum concentration of 1 microM failed to protect mice from lethal MCMV infection, perhaps because serum levels of thymidine were comparable to the drug level. Comparison of the ID50 against HCMV and the ID50 against human bone marrow progenitor cells resulted in an in vitro therapeutic ratio of 108, suggesting that TFT might offer some promise as a clinically useful anti-HCMV agent. PMID:6272627

  1. Cerebral ultrasound images in prenatal cytomegalovirus infection.

    PubMed

    Tomà, P; Magnano, G M; Mezzano, P; Lazzini, F; Bonacci, W; Serra, G

    1989-01-01

    A male newborn with prenatal cytomegalovirus infection was referred for cranial ultrasound. The cranial ultrasound demonstrated areas of increased echogenicity in the thalamic and gray nuclei resembling "a branched candlestick". Doppler technique located the "branched candlestick" along the thalamostriate arteries. This image is particularly interesting because to our knowledge it has never before been described in congenital cytomegalovirus infection, but only in congenital rubella. PMID:2550848

  2. Distinct MHC class I–dependent NK cell–activating receptors control cytomegalovirus infection in different mouse strains

    PubMed Central

    Pyzik, Michał; Charbonneau, Benoit; Gendron-Pontbriand, Eve-Marie; Babić, Marina; Krmpotić, Astrid; Jonjić, Stipan

    2011-01-01

    Recognition of mouse cytomegalovirus (MCMV)–infected cells by activating NK cell receptors was first described in the context of Ly49H, which confers resistance to C57BL/6 mice. We investigated the ability of other activating Ly49 receptors to recognize MCMV-infected cells in mice from various H-2 backgrounds. We observed that Ly49P1 from NOD/Ltj mice, Ly49L from BALB mice, and Ly49D2 from PWK/Pas mice respond to MCMV-infected cells in the context of H-2Dk and the viral protein m04/gp34. Recognition was also seen in the H-2d and/or H-2f contexts, depending on the Ly49 receptor examined, but never in H-2b. Furthermore, BALB.K (H-2k) mice showed reduced viral loads compared with their H-2d or H-2b congenic partners, a reduction which was dependent on interferon γ secretion by Ly49L+ NK cells early after infection. Adoptive transfer of Ly49L+, but not Ly49L−, NK cells significantly increased resistance against MCMV infection in neonate BALB.K mice. These results suggest that multiple activating Ly49 receptors participate in H-2–dependent recognition of MCMV infection, providing a common mechanism of NK cell–mediated resistance against viral infection. PMID:21518798

  3. Murine Cytomegalovirus Virion-Associated Protein M45 Mediates Rapid NF-κB Activation after Infection

    PubMed Central

    Krause, Eva; de Graaf, Miranda; Fliss, Patricia M.; Dölken, Lars

    2014-01-01

    ABSTRACT Murine cytomegalovirus (MCMV) rapidly induces activation of nuclear factor κB (NF-κB) upon infection of host cells. After a transient phase of activation, the MCMV M45 protein blocks all canonical NF-κB-activating pathways by inducing the degradation of the gamma subunit of the inhibitor of κB kinase complex (IKKγ; commonly referred to as the NF-κB essential modulator [NEMO]). Here we show that the viral M45 protein also mediates rapid NF-κB activation immediately after infection. MCMV mutants lacking M45 or expressing C-terminally truncated M45 proteins induced neither NF-κB activation nor transcription of NF-κB-dependent genes within the first 3 h of infection. Rapid NF-κB activation was absent in MCMV-infected NEMO-deficient fibroblasts, indicating that activation occurs at or upstream of the IKK complex. NF-κB activation was strongly reduced in murine fibroblasts lacking receptor-interacting protein 1 (RIP1), a known M45-interacting protein, but was restored upon complementation with murine RIP1. However, the ability of M45 to interact with RIP1 and NEMO was not sufficient to induce NF-κB activation upon infection. In addition, incorporation of the M45 protein into virions was required. This was dependent on a C-terminal region of M45, which is not required for interaction with RIP1 and NEMO. We propose a model in which M45 delivered by viral particles activates NF-κB, presumably involving an interaction with RIP1 and NEMO. Later in infection, expression of M45 induces the degradation of NEMO and the shutdown of canonical NF-κB activation. IMPORTANCE Transcription factor NF-κB is an important regulator of innate and adaptive immunity. Its activation can be beneficial or detrimental for viral pathogens. Therefore, many viruses interfere with NF-κB signaling by stimulating or inhibiting the activation of this transcription factor. Cytomegaloviruses, opportunistic pathogens that cause lifelong infections in their hosts, activate NF

  4. INCREASED SUSCEPTIBILITY TO PARATHION POISONING FOLLOWING MURINE CYTOMEGALOVIRUS INFECTION

    EPA Science Inventory

    Increased Susceptibility to Parathion Poisoning Following Murine Cytomegalovirus Infection. Fifty to 100 percent mortality occurred in mice treated with ordinarily sublethal doses of parathion 2 to 5 days post infection with murine cytomegalovirus (MCMV). These mortalities appear...

  5. Active human cytomegalovirus infection and glycoprotein b genotypes in brazilian pediatric renal or hematopoietic stem cell transplantation patients.

    PubMed

    de Campos Dieamant, Débora; Bonon, Sandra Helena Alves; Prates, Liliane Cury; Belangelo, Vera Maria Santoro; Pontes, Erika R; Costa, Sandra Cecília Botelho

    2010-01-01

    A prospective analysis of active Human Cytomegalovirus infection (HCMV) was conducted on 33 pediatric renal or hematopoietic stem cell post-transplant patients. The HCMV-DNA positive samples were evaluated for the prevalence of different gB subtypes and their subsequent correlation with clinical signs. The surveillance of HCMV active infection was based on the monitoring of antigenemia (AGM) and on a nested polymerase chain reaction (N-PCR) for the detection of HCMV in the patients studied. Using restriction analysis of the gB gene sequence by PCR-RFLP (Restriction Fragment Length Polymorphism), different HCMV strains could be detected and classified in at least four HCMV genotypes. Thirty-three pediatric recipients of renal or bone marrow transplantation were monitored. Twenty out of thirty-three (60.6%) patients demonstrated active HCMV infection. gB1 and gB2 genotypes were more frequent in this population. In this study, we observed that gB2 had correlation with reactivation of HCMV infection and that patients with mixture of genotypes did not show any symptoms of HCMV disease. Future studies has been made to confirm this. PMID:24031463

  6. Cytomegalovirus generates long-lived antigen-specific NK cells with diminished bystander activation to heterologous infection

    PubMed Central

    Min-Oo, Gundula

    2014-01-01

    Natural killer (NK) cells play a key role in the host response to cytomegalovirus (CMV) and can mediate an enhanced response to secondary challenge with CMV. We assessed the ability of mouse CMV (MCMV)–induced memory Ly49H+ NK cells to respond to challenges with influenza, an acute viral infection localized to the lung, and Listeria monocytogenes, a systemic bacterial infection. MCMV-memory NK cells did not display enhanced activation or proliferation after infection with influenza or Listeria, as compared with naive Ly49H+ or Ly49H− NK cells. Memory NK cells also showed impaired activation compared with naive cells when challenged with a mutant MCMV lacking m157, highlighting their antigen-specific response. Ex vivo, MCMV-memory NK cells displayed reduced phosphorylation of STAT4 and STAT1 in response to stimulation by IL-12 and type I interferon (IFN), respectively, and IFN-γ production was reduced in response to IL-12 + IL-18 compared with naive NK cells. However, costimulation of MCMV-memory NK cells with IL-12 and m157 antigen rescues their impaired response compared with cytokines alone. These findings reveal that MCMV-primed memory NK cells are diminished in their response to cytokine-driven bystander responses to heterologous infections as they become specialized and antigen-specific for the control of MCMV upon rechallenge. PMID:25422494

  7. Subclinical Congenital Cytomegalovirus Infection and Hearing Impairment

    ERIC Educational Resources Information Center

    Dahle, Arthur J.; And Others

    1974-01-01

    When the hearing sensitivity of children with subclinical congenital cytomegalovirus infection was evaluated and compared with that of a group of matched control subjects, nine of the 18 infected subjects were found to have some hearing loss, ranging from slight high-frequency impairments to a severe-to-profound unilateral loss. (MYS)

  8. Congenital cytomegalovirus infection: Clinical presentation, epidemiology, diagnosis and prevention

    PubMed Central

    van Zuylen, Wendy J; Hamilton, Stuart T; Naing, Zin; Hall, Beverly; Shand, Antonia

    2014-01-01

    Cytomegalovirus is the most common congenital infection causing serious disease in infants. It is the leading infectious cause of sensorineural hearing loss and neurodevelopmental disability in developed countries. Despite the clinical importance of congenital cytomegalovirus, surveys show there is limited awareness and knowledge in the medical and general community about congenital cytomegalovirus infection. This article reviews the clinical features, global epidemiology, transmission and risk factors for cytomegalovirus infections. It also highlights several major advances made in recent years in the diagnosis and prevention of cytomegalovirus infection during pregnancy. Although research is ongoing, no therapy is currently proven to prevent or treat maternal, fetal or neonatal cytomegalovirus infection. Education of women regarding hygiene measures can help prevent cytomegalovirus infection and are currently the best strategy to prevent congenital cytomegalovirus disease.

  9. Acquisition of cytomegalovirus infection: an update.

    PubMed Central

    Forbes, B A

    1989-01-01

    Human cytomegalovirus (CMV) is a ubiquitous deoxyribonucleic acid virus that commonly infects a majority of individuals at some time during their life. Although most of these CMV infections are asymptomatic, certain patient groups are at risk to develop serious illness. Understanding the epidemiology of this virus is a key element in the development of strategies for preventing CMV disease. However, a number of features of this virus complicate such understanding. Following infection, CMV can remain latent, with subsequent reactivation; the factors controlling latency and reactivation and those factors which determine whether a CMV infection will be symptomatic are unknown. CMV disease can be acquired by natural routes, including horizontal and vertical transmission. Due to the ubiquity of CMV, the delineation of CMV transmission by these natural routes is complicated by the myriad of possible sources. Moreover, concerns over the risk of CMV transmission to the seronegative pregnant female have been raised in relation to preventing CMV transmission. By using molecular biologic techniques, much knowledge has been gained regarding the transmission of CMV disease by natural routes; however, a number of questions remain unanswered. The transmission of CMV infection by natural routes is therefore reviewed and the issues are highlighted. Primary infection, reactivation, and reinfection are the types of active CMV infections that can occur in an immunocompromised patient. In addition to natural routes of infection, introduction of presumably latently infected organs and requirements for multiple blood transfusions increase potential exposure to CMV in the immunocompromised patient. Understanding the epidemiology of CMV infections in the immunocompromised patient is difficult and in some instances controversial due to the complexity and interdependency of a number of factors which lead to CMV infection. In an immunocompromised individual, a major risk factor in developing

  10. Cytomegalovirus Cutaneous Infection in an Immunocompromised Patient

    PubMed Central

    Pedersen, Faye T; Alhassan, Sulaiman; Adjapong, Opoku; Thirumala, Raghukumar

    2016-01-01

    Cytomegalovirus (CMV), a member of the Herpesviridae family, is an opportunistic infection with a typically benign course in the healthy host but has a more ominous course in the immunocompromised population. CMV infection commonly affects the visceral organs, particularly the respiratory and the gastrointestinal tract. CMV cutaneous lesions are rare and can be easily missed. We present a case of a 76-year-old woman presenting with a diffuse non-pruritic macular lesion with scattered vesicles and bullae, which was initially treated as a varicella zoster virus infection and herpes simplex viral infection, but was later found on biopsy to be due to cytomegalovirus. She has a history of Sjögren's syndrome, interstitial lung disease, and being on chronic immunosuppression therapy. This case highlights the importance of considering CMV infection in the differential diagnosis of vesicular skin lesions in immunocompromised patients. Based on a PubMed search for “cutaneous cytomegalovirus”, “cutaneous CMV”, “cytomegalovirus skin”, and “skin CMV” in material published in the last 20 years (from 1996 to 2016) and reviewing any applicable referenced material outside of those dates, cases of cutaneous CMV are not well documented. PMID:27335710

  11. The Association of Human Cytomegalovirus with Biomarkers of Inflammation and Immune Activation in HIV-1-Infected Women.

    PubMed

    Lurain, Nell S; Hanson, Barbara A; Hotton, Anna L; Weber, Kathleen M; Cohen, Mardge H; Landay, Alan L

    2016-02-01

    Three groups of cytomegalovirus (CMV)-seropositive women (total n = 164) were selected from the Chicago Women's Interagency HIV-1 Study to investigate the association between CMV coinfection and immune activation: (1) HIV-1 viremic, (2) HIV-1 aviremic, and (3) HIV-1 uninfected. Quantitative measures of CMV serum IgG, CMV DNA, and serum biomarkers interleukin (IL)-6, soluble CD163 (sCD163), soluble CD14 (sCD14), and interferon gamma-induced protein (IP10) were obtained. Levels of CMV IgG and the serum biomarkers were significantly higher in the HIV-1 viremic group compared to the aviremic and uninfected groups (p < 0.001). No significant associations with CMV IgG levels were found for HIV-uninfected women. When each of the HIV-infected groups was analyzed, sCD14 levels in the viremic women were significantly associated with CMV IgG levels with p < 0.02 when adjusted for age, CD4 count, and HIV viral load. There was also a modest association (p = 0.036) with IL-6 from plasma and cervical vaginal lavage specimens both unadjusted and adjusted for CD4 count and HIV viral load. The association of CMV IgG level with sCD14 implicates the monocyte as a potential site for interaction of the two viruses, which eventually may lead to non-AIDS-defining pathological conditions. PMID:26422187

  12. Thrombosis associated with acute cytomegalovirus infection: a narrative review

    PubMed Central

    Sherman, Shany; Eytan, Ori

    2014-01-01

    Thrombosis associated with acute cytomegalovirus infection has been reported many times in the literature since the mid 1980s – mainly in case reports and in small case series, but also in four controlled studies. Still, many physicians are unaware of this association although acute cytomegalovirus infection diagnosis in a thrombosis patient may warrant antiviral therapy and may affect anticoagulation therapy duration. Accordingly, the clinical characteristics of patients with thrombosis and acute cytomegalovirus infection are reviewed, and the current knowledge concerning this unique association is presented herein. We believe it is time to add acute cytomegalovirus infection to the list of thrombosis triggers. PMID:25624857

  13. Triple drug immunosuppression significantly reduces immune activation and allograft arteriosclerosis in cytomegalovirus-infected rat aortic allografts and induces early latency of viral infection.

    PubMed Central

    Lemström, K. B.; Bruning, J. H.; Bruggeman, C. A.; Lautenschlager, I. T.; Häyry, P. J.

    1994-01-01

    The effect of triple drug immunosuppression (cyclosporine A 10 mg/kg/day+methylprednisolone 0.5 mg/kg/day+azathioprine 2 mg/kg/day) on rat cytomegalovirus (RCMV)-enhanced allograft arteriosclerosis was investigated applying WF (AG-B2, RT1v) recipients of DA (AG-B4, RT1a) aortic allografts. The recipients were inoculated intraperitoneally with 10(5) plaque-forming units of RCMV 1 day after transplantation or left noninfected. The grafts were removed on 7 and 14 days, and at 1, 3, and 6 months after transplantation. The presence of viral infection was demonstrated by plaque assays, cell proliferation by [3H]thymidine autoradiography, and vascular wall alterations by quantitative histology and immunohistochemistry. Triple drug immunosuppression reduced the presence of infectious virus in plaque assays and induced early latency of viral infection. It significantly reduced the peak adventitial inflammatory response (P < 0.05) and reduced and delayed intimal nuclear intensity and intimal thickening (P < 0.05) in RCMV-infected allografts. The proliferative response of smooth muscle cells was reduced by triple drug immunosuppression to 50% of that observed in nonimmunosuppressed RCMV-infected allografts, but still the proliferative peak response was seen at 1 month. Only low level immune activation, ie, the expression of interleukin-2 receptor (P < 0.05) and MHC class II, was observed under triple drug immunosuppression in the adventitia of RCMV-infected allografts, whereas there was no substantial change in the phenotypic distribution of inflammatory cells. In conclusion, although RCMV infection significantly enhances allograft arteriosclerosis also in immunosuppressed allografts, triple drug immunosuppression has no additional detrimental effect but rather a protective one on vascular wall histology. These results further suggest that RCMV-enhanced allograft arteriosclerosis may be an immunopathological condition linked to the host immune response toward the graft and

  14. Transient activation of human cytomegalovirus lytic gene expression during latency allows cytotoxic T cell killing of latently infected cells

    PubMed Central

    Krishna, B. A.; Lau, B.; Jackson, S. E.; Wills, M. R.; Sinclair, J. H.; Poole, E.

    2016-01-01

    Human cytomegalovirus (HCMV) latency in the myeloid lineage is maintained by repressive histone modifications around the major immediate early promoter (MIEP), which results in inhibition of the lytic viral life cycle. We now show that pharmacological inhibition of histone deacetylases (HDACs) relieves this repression of the MIEP and induces transient expression of the viral lytic immediate early (IE) antigens but, importantly, not full virus reactivation. In turn, these latently infected cells now become targets for IE-specific cytotoxic T cells (CTLs) which are present at high frequency in all normal healthy HCMV positive carriers but would normally be unable to target latent (lytic antigen-negative) cells. This approach of transiently inducing viral lytic gene expression by HDAC inhibition, in otherwise latently infected cells, offers a window of opportunity to target and purge the latent myeloid cell reservoir by making these normally immunologically undetectable cells visible to pre-existing host immune responses to viral lytic antigens. PMID:27091512

  15. Transient activation of human cytomegalovirus lytic gene expression during latency allows cytotoxic T cell killing of latently infected cells.

    PubMed

    Krishna, B A; Lau, B; Jackson, S E; Wills, M R; Sinclair, J H; Poole, E

    2016-01-01

    Human cytomegalovirus (HCMV) latency in the myeloid lineage is maintained by repressive histone modifications around the major immediate early promoter (MIEP), which results in inhibition of the lytic viral life cycle. We now show that pharmacological inhibition of histone deacetylases (HDACs) relieves this repression of the MIEP and induces transient expression of the viral lytic immediate early (IE) antigens but, importantly, not full virus reactivation. In turn, these latently infected cells now become targets for IE-specific cytotoxic T cells (CTLs) which are present at high frequency in all normal healthy HCMV positive carriers but would normally be unable to target latent (lytic antigen-negative) cells. This approach of transiently inducing viral lytic gene expression by HDAC inhibition, in otherwise latently infected cells, offers a window of opportunity to target and purge the latent myeloid cell reservoir by making these normally immunologically undetectable cells visible to pre-existing host immune responses to viral lytic antigens. PMID:27091512

  16. Optimum treatment of congenital cytomegalovirus infection.

    PubMed

    Leruez-Ville, Marianne; Ville, Yves

    2016-01-01

    Congenital cytomegalovirus infection affects 0.7% of live births and is the leading cause of congenital neurological handicaps of infectious origin. However, systematic screening of this infection has not been implemented in pregnancy or at birth in any country. This apparent paradox has been justified by the unavailability of an efficient vaccine and by the scarcity of data available on the treatment of congenital CMV. However, in the last decade interesting new data on the management of this congenital infection has emerged including new results on both neonatal and postnatal treatments. This review provides an update on the potential benefits of antiviral treatment and on passive immunisation both in the neonatal and the antenatal periods. These suggest a benefit to a proactive approach for neonatal and prenatal congenital infections. PMID:27043943

  17. Suppressive effects of sirtinol on human cytomegalovirus (hCMV) infection and hCMV-induced activation of molecular mechanisms of senescence and production of reactive oxygen species.

    PubMed

    Mao, Genxiang; Li, Huifen; Ding, Xiang; Meng, Xin; Wang, Guofu; Leng, Sean X

    2016-09-01

    Substantial evidence suggests that chronic human cytomegalovirus (hCMV) infection contributes significantly to T-cell immunosenescence and adverse health outcomes in older adults. As such, it is important to search for compounds with anti-hCMV properties. Studies have shown that resveratrol, a sirtuin activator, suppresses hCMV infection. Here we report suppressive effects of sirtinol, a sirtuin antagonist, on hCMV infection and its cellular and molecular consequences. Human diploid fibroblast WI-38 cells were infected by hCMV Towne strain in the absence or presence of sirtinol. hCMV replication was measured using qPCR. Senescent phenotype was determined by senescence-associated β galactosidase (SA-β-Gal) activity. Expression of hCMV immediate early (IE) and early (E) proteins and senescence-associated proteins (pRb and Rb, p16(INK4), and p53) and production of reactive oxygen species (ROS) were assessed using standard laboratory assays. The results demonstrated that sirtinol suppressed hCMV infection as well as hCMV-induced activation of molecular mechanisms of senescence and ROS production. While underlying molecular mechanisms remain to be elucidated, these findings indicate sirtinol as a novel and potent anti-hCMV agent with the potential to be developed as an effective treatment for chronic hCMV infection and its cellular and molecular consequences that are important to ageing and health of older adults. PMID:26763147

  18. An animal model of human cytomegalovirus infection.

    PubMed

    Gao, L; Qian, S; Zeng, L; Wang, R; Wei, G; Fan, J; Zheng, S

    2007-12-01

    To develop a rat model that allowed in vivo progressive human cytomegalovirus (HCMV) infection, allogeneic liver transplantation was performed across a rat combination of Dark Agouti (DA) to Brown Norway (BN). AD169, a well-characterized laboratory strain of HCMV, was used to establish a rat model of HCMV infection by injection of 0.4 mL (30.0 logTCID50) supernate into the rat peritoneum. Histological and blood specimens were obtained from animals sacrificed at predetermined timepoints. We performed immunohistochemical staining in liver, heart, kidney, spleen, and lung for HCMV immediate-early antigen (IE), lower matrix protein (pp65) detection in peripheral blood leukocytes, and HCMV early antigen (EA) and late antigen (LA). We compared survival rates. Our results showed positive HCMV IE and pp65 antigenemia detected in peripheral blood leukocytes in transplanted recipients from day 1 to day 30. Positive HCMV EA and LA staining cells were only detected in sections 10 days after liver transplantation, namely, in hepatocytes, mononuclear cells, bile duct epithelial cells, and endothelial cells. Successful HCMV replication was due to the combination of liver transplantation and cyclosporine (CsA) immunosuppression. Survival analysis showed no significant differences between the HCMV-infected group and HCMV-uninfected group. This new rat model of HCMV infection may be helpful to understand immune system modulation of HCMV infection. PMID:18089401

  19. Pathogenesis of Experimental Rhesus Cytomegalovirus Infection

    PubMed Central

    Lockridge, Kristen M.; Sequar, Getachew; Zhou, Shan Shan; Yue, Yujuan; Mandell, Carol P.; Barry, Peter A.

    1999-01-01

    Human cytomegalovirus (HCMV) establishes and maintains a lifelong persistence following infection in an immunocompetent host. The determinants of a stable virus-host relationship are poorly defined. A nonhuman primate model for HCMV was used to investigate virological and host parameters of infection in a healthy host. Juvenile rhesus macaques (Macaca mulatta) were inoculated with rhesus cytomegalovirus (RhCMV), either orally or intravenously (i.v.), and longitudinally necropsied. None of the animals displayed clinical signs of disease, although hematologic abnormalities were observed intermittently in i.v. inoculated animals. RhCMV DNA was detected transiently in the plasma of all animals at 1 to 2 weeks postinfection (wpi) and in multiple tissues beginning at 2 to 4 wpi. Splenic tissue was the only organ positive for RhCMV DNA in all animals. The location of splenic cells expressing RhCMV immediate-early protein 1 (IE1) in i.v. inoculated animals changed following inoculation. At 4 to 5 wpi, most IE1-positive cells were perifollicular, and at 25 wpi, the majority were located within the red pulp. All animals developed anti-RhCMV immunoglobulin M (IgM) antibodies within 1 to 2 wpi and IgG antibodies within 2 to 4 wpi against a limited number of viral proteins. Host reactivity to RhCMV proteins increased in titer (total and neutralizing) and avidity with time. These results demonstrate that while antiviral immune responses were able to protect from disease, they were insufficient to eliminate reservoirs of persistent viral gene expression. PMID:10516066

  20. Progressive Hearing Impairment in Children with Congenital Cytomegalovirus Infection.

    ERIC Educational Resources Information Center

    Dahle, Arthur J.; And Others

    1979-01-01

    Audiological assessment of 86 children (mean age 38 months at last evaluation time) with congenital cytomegalovirus infection revealed progressive hearing loss in four of 12 Ss with sensorineural hearing impairments. Case descriptions documented the progression of the hearing loss. (Author)

  1. Activating Receptors for Self-MHC Class I Enhance Effector Functions and Memory Differentiation of NK Cells during Mouse Cytomegalovirus Infection.

    PubMed

    Nabekura, Tsukasa; Lanier, Lewis L

    2016-07-19

    Natural killer (NK) cells are important in host defense against pathogens, and they can subsequently differentiate into memory NK cells. The Ly49 and KIR gene families in rodents and humans encode both inhibitory and activating receptors for MHC class I. The physiological role of activating KIR or Ly49 receptors that recognize self-MHC class I during immune response to viral infections is unknown. Here, we address how the activating Ly49D receptor impacts the NK cell response to mouse cytomegalovirus (MCMV) infection by comparing the activation and differentiation of Ly49D-bearing NK cells in mice lacking or expressing H-2D(d), the cognate MHC class I ligand of Ly49D. After MCMV infection, Ly49D augmented IFN-γ production by MCMV-specific Ly49H(+) NK cells and preferentially promoted the generation of memory Ly49H(+) NK cells. Thus, activating receptors for self-MHC class I modulate the differentiation of MCMV-specific NK cells and are beneficial for host defense against MCMV infection. PMID:27438766

  2. Animal cytomegaloviruses.

    PubMed Central

    Staczek, J

    1990-01-01

    Cytomegaloviruses are agents that infect a variety of animals. Human cytomegalovirus is associated with infections that may be inapparent or may result in severe body malformation. More recently, human cytomegalovirus infections have been recognized as causing severe complications in immunosuppressed individuals. In other animals, cytomegaloviruses are often associated with infections having relatively mild sequelae. Many of these sequelae parallel symptoms associated with human cytomegalovirus infections. Recent advances in biotechnology have permitted the study of many of the animal cytomegaloviruses in vitro. Consequently, animal cytomegaloviruses can be used as model systems for studying the pathogenesis, immunobiology, and molecular biology of cytomegalovirus-host and cytomegalovirus-cell interactions. PMID:2170830

  3. Seroprevalence and Risk Factors for Cytomegalovirus Infections in Adolescent Females

    PubMed Central

    Stadler, Laura Patricia; Bernstein, David I.; Callahan, S. Todd; Turley, Christine B.; Munoz, Flor M.; Ferreira, Jennifer; Acharya, Mekhala; Simone, Gina A. Gorgone; Patel, Shital M.; Edwards, Kathryn M.; Rosenthal, Susan L.

    2013-01-01

    Background Congenital cytomegalovirus (CMV) is a leading cause of disability, including sensorineural hearing loss, developmental delay, and mental retardation. Understanding risk factors for acquisition of CMV infection in adolescent females will help determine vaccine strategies. Methods Females (12–17 years) were recruited from primary care settings in Cincinnati, Galveston, Houston, and Nashville from June 2006 to July 2010 for a seroepidemiologic study, from which seronegative participants were recruited for a CMV vaccine trial. Participants (n = 1585) responded to questions regarding potential exposures. For those with young children in the home (n = 859), additional questions were asked about feeding and changing diapers, and for those > 14 years of age (n = 1162), questions regarding sexual activity were asked. Serum was evaluated for CMV antibody using a commercial immunoglobulin G assay. Results Cytomegalovirus antibody was detected in 49% of participants. In the univariate analyses, CMV seroprevalence was significantly higher among African Americans, those with children < 3 years of age in the home, and those with a history of oral, anal, or vaginal intercourse. Among those with young children in the home, feeding children and changing diapers further increased the association with CMV infection. However, in the final multivariate analysis, only African Americans and household contact with young children were associated with CMV infection. Conclusions By age 12, evidence of CMV infection was common. Multiple factors regarding race and personal behaviors likely contribute to seroconversion earlier in life. PMID:23687583

  4. Peptide inhibition of human cytomegalovirus infection

    PubMed Central

    2011-01-01

    Background Human cytomegalovirus (HCMV) is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV)- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB), a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS), several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF) were infected with the Towne-GFP strain of HCMV (0.5 MOI), preincubated with peptides at a range of concentrations (78 nm to 100 μM), and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100 μM and 50 μM, respectively

  5. Increased intestinal permeability during cytomegalovirus infection in renal transplant recipients.

    PubMed

    de Maar, E F; Kleibeuker, J H; Boersma-van Ek, W; The, T H; van Son, W J

    1996-01-01

    Cytomegalovirus (CMV) infections in renal transplant recipients can affect the gastrointestinal tract, but significant clinical manifestations are seldom seen. We hypothesize that subclinical involvement of the gastrointestinal tract may be quite frequent during CMV infection. In order to study this, we measured intestinal permeability by calculating the urinary lactulose mannitol (LM) excretion ratio after oral administration of lactulose and mannitol (normal < 0.030) in patients with symptomatic and asymptomatic CMV infection. A total of 111 patients were enrolled in the study, 104 of whom were tested on postoperative day (POD) 10. Twenty-nine patients developed CMV infection, 12 of whom could be studied with the permeability test (median POD 40). Another nine patients without CMV infection were also studied at day 40 and served as controls. The LM ratio increased significantly during CMV infection compared to measurements before active infection (median 0.060 vs. 0.030, P < 0.01) and was significantly higher during the infection than in the control group (median 0.007, P < 0.01). No correlation could be found between the LM ratio and viral load, humoral response to the virus, or symptomatology of infection. We conclude that an increased intestinal permeability is found in a substantial number of patients with an active, albeit asymptomatic, CMV infection after renal transplantation. Pathophysiological mechanisms and clinical implications remain speculative but will be subject to further study. PMID:8914238

  6. Cytomegalovirus infection in pregnancy: review of the literature

    PubMed Central

    Bonalumi, Silvia; Trapanese, Angelica; Santamaria, Angelo; D’Emidio, Laura; Mobili, Luisa

    2011-01-01

    The aim of this review is to summarize the principles of cytomegalovirus (CMV) infection in pregnancy. In particular, the aim of this review is to evaluate: Incidence and mother-to-child transmissionThe value of screening of pregnant womenDiagnosis of CMV maternal infectionDiagnosis of fetal infection (evaluate the value of ultrasound examination and amniocentesis and evaluate whether the amniotic viral load of mothers with primary cytomegalovirus infection correlate with fetal or neonatal outcomes)Diagnosis of infection in newbornsTherapy in pregnancy, postnatal therapy and prevention PMID:22439067

  7. Brief Report: Autistic Disorder in Three Children with Cytomegalovirus Infection

    ERIC Educational Resources Information Center

    Sweeten, Thayne L.; Posey, David J.; McDougle, Christopher J.

    2004-01-01

    Previous research has identified a relationship between autistic disorder (autism) and specific congenital infections. Three cases of congenital or perinatal cytomegalovirus (CMV) infection occurring in association with autism are described. Hypothetical mechanisms relating congenital infection, such as CMV, to the development of autism are…

  8. Surveillance of active human cytomegalovirus infection in hematopoietic stem cell transplantation (HLA sibling identical donor): search for optimal cutoff value by real-time PCR

    PubMed Central

    2010-01-01

    Background Human cytomegalovirus (CMV) infection still causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, it is extremely important to diagnosis and monitor active CMV infection in HSCT patients, defining the CMV DNA levels of virus replication that warrant intervention with antiviral agents in order to accurately prevent CMV disease and further related complications. Methods During the first 150 days after allogeneic HSTC, thirty patients were monitored weekly for active CMV infection by pp65 antigenemia, nested-PCR and real-time PCR assays. Receiver operating characteristic (ROC) plot analysis was performed to determine a threshold value of the CMV DNA load by real-time PCR. Results Using ROC curves, the optimal cutoff value by real-time PCR was 418.4 copies/104 PBL (sensitivity, 71.4%; specificity, 89.7%). Twenty seven (90%) of the 30 analyzed patients had active CMV infection and two (6.7%) developed CMV disease. Eleven (40.7%) of these 27 patients had acute GVHD, 18 (66.7%) had opportunistic infection, 5 (18.5%) had chronic rejection and 11 (40.7%) died - one died of CMV disease associated with GVHD and bacterial infection. Conclusions The low incidence of CMV disease in HSCT recipients in our study attests to the efficacy of CMV surveillance based on clinical routine assay. The quantification of CMV DNA load using real-time PCR appears to be applicable to the clinical practice and an optimal cutoff value for guiding timely preemptive therapy should be clinically validated in future studies. PMID:20515464

  9. Prevention of Primary Cytomegalovirus Infection in Pregnancy☆

    PubMed Central

    Revello, Maria Grazia; Tibaldi, Cecilia; Masuelli, Giulia; Frisina, Valentina; Sacchi, Alessandra; Furione, Milena; Arossa, Alessia; Spinillo, Arsenio; Klersy, Catherine; Ceccarelli, Manuela; Gerna, Giuseppe; Todros, Tullia

    2015-01-01

    Background Cytomegalovirus (CMV) is the leading infectious agent causing congenital sensorineural hearing loss and psychomotor retardation. CMV vaccine is currently unavailable and treatment options in pregnancy are limited. Susceptible pregnant women caring for children are at high risk for primary infection. CMV educational and hygienic measures have the potential to prevent primary maternal infection. Methods A mixed interventional and observational controlled study was conducted to investigate the effectiveness of hygiene information among pregnant women at risk for primary CMV infection for personal/occupational reasons. In the intervention arm, CMV-seronegative women, identified at the time of maternal serum screening for fetal aneuploidy at 11–12 weeks of gestation, were given hygiene information and prospectively tested for CMV until delivery. The comparison arm consisted of women enrolled at delivery who were neither tested for nor informed about CMV during pregnancy, and who had a serum sample stored at the screening for fetal aneuploidy. By design, groups were homogeneous for age, parity, education, and exposure to at least one risk factor. The primary outcome was CMV seroconversion. Acceptance of hygiene recommendations was a secondary objective and was measured by a self-report. Findings Four out of 331 (1.2%) women seroconverted in the intervention group compared to 24/315 (7.6%) in the comparison group (delta = 6.4%; 95% CI 3.2–9.6; P < 0.001). There were 3 newborns with congenital infection in the intervention group and 8 in the comparison group (1 with cerebral ultrasound abnormalities at birth). Ninety-three percent of women felt hygiene recommendations were worth suggesting to all pregnant women at risk for infection. Interpretation This controlled study provides evidence that an intervention based on the identification and hygiene counseling of CMV-seronegative pregnant women significantly prevents maternal infection. While waiting for

  10. Ileal perforation caused by cytomegalovirus infection in an immunocompetent adult.

    PubMed

    Van Schaeybroeck, S; Hiele, M; Miserez, M; Croes, R

    2002-01-01

    A 71-year-old woman developed a small bowel perforation due to cytomegalovirus infection. She did not taken any immunosuppressive medication and her cellular immunity was normal. Surgical resection and antiviral therapy with ganciclovir led to complete recovery. As far as we know, this paper reports the first case of small bowel perforation due to cytomegalovirus infection in a non-immunocompromised patient. Nevertheless the patient was known with diabetes mellitus. It should be emphasised that elderly patients have impaired immune defences and may be unsuspected hosts of opportunistic infections. PMID:12212357

  11. Autism in a Child with Congenital Cytomegalovirus Infection.

    ERIC Educational Resources Information Center

    Markowitz, Phillip I.

    1983-01-01

    A case study is described in which early infantile autism was diagnosed in a child with congenital cytomegalovirus (CMU) infection. It is suggested that congenital infection should be considered as an etiological agent in autism. The case's synergistic effect of CMU-induced brain damage, deafness, and maternal deprivation in noted. (CL)

  12. Cytomegalovirus (CMV) Infection: A Guide for Patients and Families After Stem Cell Transplant

    MedlinePlus

    ... Infection: A Guide for Patients and Families after Stem Cell Transplant What is cytomegalovirus (CMV)? Cytomegalovirus (CMV), a ... weakened by medicines that you must take after stem cell transplant and by the transplant itself. Your body ...

  13. Bone marrow atrophy induced by murine cytomegalovirus infection.

    PubMed Central

    Gibbons, A E; Price, P; Shellam, G R

    1994-01-01

    Acute, sublethal infection of mice with murine cytomegalovirus (MCMV) resulted in up to 80% decreases in the number of cells recoverable from the bone marrow, and a decrease in peripheral blood leucocyte counts during the first week of infection. Depopulation of the leucopoietic areas of the marrow was evident from examination of histological sections. The severity of bone marrow atrophy in MCMV-infected mice of different strains correlated with previously described genetically determined sensitivity to MCMV disease. Although the phenomenon only occurred when mice were inoculated with infectious virus preparations, fewer than one in 10(5) marrow cells were productively infected, suggesting that atrophy was not due to lytic infection of large numbers of bone marrow cells. Interestingly, increases in serum colony-stimulating activity were observed and these were proportional to the severity of bone marrow atrophy. After MCMV infection, we observed increases in the proportions of cells expressing some B-cell and myeloid cell markers and a decrease in the proportion of cells expressing an erythroid cell marker. There was no change in the frequency of marrow cells expressing mature T-cell markers. The numbers of myeloid lineage-committed progenitor cells (GM-CFU) in the marrow decreased 10- to 20-fold in BALB/c nu/+ mice, while there was a threefold decrease in their numbers in BALB/c nu/nu mice. In addition, increases in serum colony-stimulating activity were greater in BALB/c nu/+ mice than in BALB/c nu/nu mice. Our results suggest that growth factors produced after MCMV infection may accelerate the maturation and migration of cells from the marrow to sites of virus replication and inflammation, thus accounting for the depletion in numbers of marrow cells observed soon after MCMV infection. Images Figure 3 Figure 4 PMID:7959876

  14. Infantile Spasms and Cytomegalovirus Infection: Antiviral and Antiepileptic Treatment

    ERIC Educational Resources Information Center

    Dunin-Wasowicz, Dorota; Kasprzyk-Obara, Jolanta; Jurkiewicz, Elzbieta; Kapusta, Monika; Milewska-Bobula, Bogumila

    2007-01-01

    From 1 January 1995 to 31 December 2004, 22 patients (13 males, nine females; age range 2-12mo) with infantile spasms and cytomegalovirus (CMV) infection were treated with intravenous ganciclovir (GCV) and antiepileptic drugs. GCV was given for 3 to 12 weeks with a 1-month interval (one, two, or three courses). Epileptic spasms occurred before…

  15. [Cytomegalovirus and BK polyomavirus infection after renal transplantation].

    PubMed

    De Paolis, P; Gervasio, E; Tedesco, M; Favaro', A; Iappelli, M; Di Giulio, S

    2009-01-01

    Cytomegalovirus (CMV) and BK polyomavirus (BKV) infections have been described in a high percentage of renal transplant patients and are known to cause various complications in renal transplantation. They are closely related to immunosuppressive therapy and implicated in the progression of graft failure. This review focuses on the clinical aspects of CMV and BKV infection after renal transplantation, optimal monitoring, and recent preventive measures and interventions to improve graft function and recipient survival. PMID:19382094

  16. Efficacy and Safety of a Preemptive Antiviral Therapy Strategy Based on Combined Virological and Immunological Monitoring for Active Cytomegalovirus Infection in Allogeneic Stem Cell Transplant Recipients

    PubMed Central

    Navarro, David; Amat, Paula; de la Cámara, Rafael; López, Javier; Vázquez, Lourdes; Serrano, David; Nieto, José; Rovira, Monserrat; Piñana, José Luis; Giménez, Estela; Solano, Carlos

    2016-01-01

    Background. Preemptive antiviral therapy for active cytomegalovirus (CMV) infection in allogeneic stem cell transplant recipients (Allo-SCT) results in overtreatment and a high rate of recurrences. Monitoring of CMV-specific T-cell immunity may help to individualize treatments and minimize these problems. Methods. We conducted a prospective, multicenter, matched comparison-group study to evaluate the efficacy and safety of a novel strategy that consisted of interrupting anti-CMV therapy upon CMV DNAemia clearance and concurrent detection of phosphoprotein 65/immediate-early-1-specific interferon-γ-producing CD8+ T cells at levels of >1 cell/µL (within 30 days after the initiation of therapy). Immunological monitoring was performed on days +7, +14, +21, and +28 after treatment initiation. The primary endpoint was the cumulative incidence of recurrent DNAemia within 2 months after treatment cessation. Secondary endpoints were the length of antiviral treatment courses and the incidence of hematological toxicity. Results. Sixty-one patients were enrolled in the study group. Fifty-six patients were included in the matched-control group. Eleven patients (18%) fulfilled the criteria for antiviral treatment interruption. The cumulative incidence of recurrent CMV DNAemia was significantly lower (P = .02) in these patients than in patients in the comparative groups. Likewise, the length of antiviral treatment courses was significantly shorter in these patients than that in patients in the matched-control group (P = .003). No significant differences in the incidence of hematological toxicity was observed between the comparative groups. Conclusions. Our data support the clinical utility of combining immunological and virological monitoring for the management of CMV infection in a subset of Allo-SCT recipients. PMID:27419179

  17. Guillain-Barré syndrome and cytomegalovirus infection during pregnancy.

    PubMed

    Lupo, Julien; Germi, Raphaële; Jean, Dominique; Baccard-Longère, Monique; Casez, Olivier; Besson, Gérard; Rougé, Alain; Boutonnat, Jean; Schwebel, Carole; Hoffmann, Pascale; Morand, Patrice

    2016-06-01

    Guillain-Barré syndrome (GBS) is an immune-mediated disorder which can be triggered by cytomegalovirus (CMV) infection. GBS following CMV primary infection is a rare event during pregnancy, which raises the question of maternal and fetal management. We describe an unusual case of GBS after CMV primary infection in a pregnant woman. The mother was successfully treated with standard immunoglobulins but in utero fetal death caused by CMV congenital infection unfortunately occurred. Similar cases have rarely been reported in the literature. PMID:27105316

  18. Congenital cytomegalovirus infection: a cause of renal dysplasia?

    PubMed

    Chan, Maren; Hecht, Jonathan L; Boyd, Theonia; Rosen, Seymour

    2007-01-01

    Cytomegalovirus (CMV) infection is one of the most frequently encountered viral infections of the fetus and induces a wide range of histologic and clinical manifestations. Congenital abnormalities are typically restricted to the central nervous system despite evidence of CMV inclusions occurring in most epithelial cells. Although tissue injury and even glomerulonephritis have been observed in congenital CMV infections, renal multicystic dysplasia has not been reported. Herein, we describe a case of unilateral renal dysplasia in a 19-week fetus with concurrent CMV infection. We believe the present case to be the first description of a virus apparently inducing renal multicystic dysplasia. PMID:17638423

  19. Non-cytomegalovirus ocular opportunistic infections in patients with AIDS

    PubMed Central

    Gangaputra, Sapna; Drye, Lea; Vaidya, Vijay; Thorne, Jennifer E.; Jabs, Douglas A; Lyon, Alice T.

    2014-01-01

    Purpose To report the incidence and clinical outcomes of non-cytomegalovirus (non-CMV) ocular opportunistic infections in patients with AIDS in the era of highly active antiretroviral therapy (HAART). Design Multicenter, prospective, observational study of patients with AIDS Methods Medical history, ophthalmologic examination, and laboratory tests were performed at enrollment and every 6 months subsequently. Once an ocular opportunistic infection was diagnosed, patients were seen every 3 months for outcomes. Results At enrollment, 37 non-CMV ocular opportunistic infections were diagnosed: 16 patients, herpetic retinitis; 11 patients, toxoplasmic retinitis; and 10 patients, choroiditis. During the follow-up period, the estimated incidences (and 95% confidence intervals [CI]) of these were: herpetic retinitis, 0.007/100 person-years (PY) (95% CI 0.0004, 0.039); toxoplasmic retinitis, 0.007/100 PY (95% CI 0.004, 0.039); and choroiditis 0.014/100 PY (95% CI 0.0025, 0.050). The mortality rates appeared higher among those patients with newly diagnosed or incident herpetic retinitis and choroiditis (rates=21.7 deaths/100 PY [P=0.02] and 12.8 deaths/100 PY [P=0.04]) respectively, than that for patients with AIDS without an ocular opportunistic infection (4.1 deaths/100 PY); Toxoplasmic retinitis did not appear to be associated with greater mortality (6.4/100 PY, P=0.47). Eyes with newly-diagnosed herpetic retinitis appeared to have a poor visual prognosis with high rates of visual impairment (37.9/100 PY) and blindness (17.5/100 PY), whereas those outcomes in eyes with choroiditis appeared to be lower (2.3/100 PY and 0/100 PY, respectively). Conclusions Although uncommon, non-CMV ocular opportunistic infections may be associated with high rates of visual loss and/or mortality. PMID:23068916

  20. Bioactive Molecules Released From Cells Infected with the Human Cytomegalovirus

    PubMed Central

    Luganini, Anna; Terlizzi, Maria E.; Gribaudo, Giorgio

    2016-01-01

    Following primary infection in humans, the human cytomegalovirus (HCMV) persists in a latent state throughout the host’s lifetime despite a strong and efficient immune response. If the host experiences some form of immune dysregulation, such as immunosuppression or immunodeficiency, HCMV reactivates, thereby emerging from latency. Thus, in the absence of effective functional immune responses, as occurs in immunocompromised or immunoimmature individuals, both HCMV primary infections and reactivations from latency can cause significant morbidity and mortality. However, even in immunocompetent hosts, HCMV represents a relevant risk factor for the development of several chronic inflammatory diseases and certain forms of neoplasia. HCMV infection may shift between the lytic and latent state, regulated by a delicate and intricate balance between virus-mediated immunomodulation and host immune defenses. Indeed, HCMV is a master in manipulating innate and adaptive host defense pathways, and a large portion of its genome is devoted to encoding immunomodulatory proteins; such proteins may thus represent important virulence determinants. However, the pathogenesis of HCMV-related diseases is strengthened by the activities of bioactive molecules, of both viral and cellular origin, that are secreted from infected cells and collectively named as the secretome. Here, we review the state of knowledge on the composition and functions of HCMV-derived secretomes. In lytic infections of fibroblasts and different types of endothelial cells, the majority of HCMV-induced secreted proteins act in a paracrine fashion to stimulate the generation of an inflammatory microenvironment around infected cells; this may lead to vascular inflammation and angiogenesis that, in turn, foster HCMV replication and its dissemination through host tissues. Conversely, the HCMV secretome derived from latently infected hematopoietic progenitor cells induces an immunosuppressive extracellular environment that

  1. Bioactive Molecules Released From Cells Infected with the Human Cytomegalovirus.

    PubMed

    Luganini, Anna; Terlizzi, Maria E; Gribaudo, Giorgio

    2016-01-01

    Following primary infection in humans, the human cytomegalovirus (HCMV) persists in a latent state throughout the host's lifetime despite a strong and efficient immune response. If the host experiences some form of immune dysregulation, such as immunosuppression or immunodeficiency, HCMV reactivates, thereby emerging from latency. Thus, in the absence of effective functional immune responses, as occurs in immunocompromised or immunoimmature individuals, both HCMV primary infections and reactivations from latency can cause significant morbidity and mortality. However, even in immunocompetent hosts, HCMV represents a relevant risk factor for the development of several chronic inflammatory diseases and certain forms of neoplasia. HCMV infection may shift between the lytic and latent state, regulated by a delicate and intricate balance between virus-mediated immunomodulation and host immune defenses. Indeed, HCMV is a master in manipulating innate and adaptive host defense pathways, and a large portion of its genome is devoted to encoding immunomodulatory proteins; such proteins may thus represent important virulence determinants. However, the pathogenesis of HCMV-related diseases is strengthened by the activities of bioactive molecules, of both viral and cellular origin, that are secreted from infected cells and collectively named as the secretome. Here, we review the state of knowledge on the composition and functions of HCMV-derived secretomes. In lytic infections of fibroblasts and different types of endothelial cells, the majority of HCMV-induced secreted proteins act in a paracrine fashion to stimulate the generation of an inflammatory microenvironment around infected cells; this may lead to vascular inflammation and angiogenesis that, in turn, foster HCMV replication and its dissemination through host tissues. Conversely, the HCMV secretome derived from latently infected hematopoietic progenitor cells induces an immunosuppressive extracellular environment that

  2. Cytomegalovirus Infection After Intestinal Transplantation in Children

    PubMed Central

    Bueno, Javier; Green, Michael; Kocoshis, Samuel; Furukawa, Hiroyuki; Ahu-Elmagd, Kareem; Yunis, Eduardo; Irish, William; Todo, Satoru; Reyes, Jorge; Starzl, Thomas E.

    2010-01-01

    Sixteen episodes of cytomegalovirus (CMV) disease occurred in 10 of 41 children undergoing intestinal transplantation from 1990 to 1995. Stratification of CMV disease by donor (D)/recipient (R) serological status was as follows: 3 of 8, D+/R−; 3 of 9, D+/R+; 4 of 9, D−/R+; and 0 of 15, D−/R−. Treatment resulted in resolution of CMV disease in 93.3% of episodes. No deaths attributable to CMV disease occurred in this series. CMV in D+/R− children resulted in more extensive and persistent disease. However, patient and graft survival rates were similar in the different D/R subgroups and between children with and without CMV disease. Cumulative dose of steroid boluses (relative risk [RR]. 1.59; 95% confidence interval [CI]. 1.14–2.21) and history of steroid recycles (RR, 2.72; 95% CI, 1.21–6.13) were associated with CMV disease. These results suggest that although CMV-associated morbidity in pediatric intestinal transplant recipients was substantial, it was not associated with an increased rate of mortality or graft loss, even among high-risk D+/R− patients. PMID:9402361

  3. Cutaneous involvement by cytomegalovirus in a renal transplant recipient as an indicator of severe systemic infection*

    PubMed Central

    Neumann, Antonielle Borges Faria; Daxbacher, Egon Luiz Rodrigues; Chiaratti, Francielle Chiavelli; Jeunon, Thiago

    2016-01-01

    Cytomegalovirus is an opportunistic virus that commonly affects immunosuppressed patients. Cutaneous involvement by this virus is rare and occurs in significantly immunocompromised hosts, with a poor prognosis. Skin ulcers may represent the first sign of systemic infection by cytomegalovirus in these patients. Herein, a case of a systemic infection by Cytomegalovirus presenting as genital and oral ulcers in a kidney-transplant recipient is reported. PMID:26982783

  4. [Successful treatment of congenital cytomegalovirus infection with valganciclovir].

    PubMed

    Ishida, Yu; Miyajima, Tasuku; Shimura, Masaru; Morichi, Shinichiro; Morishima, Yasuyuki; Ioi, Hiroaki; Oana, Shingo; Yamanaka, Gaku; Kawashima, Hisashi; Hoshika, Akinori

    2012-01-01

    Congenital cytomegalovirus (CMV) infection occurs frequently in neonates. However, there are no screening tests or definitive treatments for this infection in Japan. We report a case of a 21-day-old Japanese boy with congenital CMV infection. He was referred to our hospital for treatment of congenital bilateral deafness. Brain magnetic resonance imaging (MRI) revealed cortical dysplasia of the temporal poles, enlarged ventricles, and areas of abnormal intensity in the white matter. He was given a diagnosis of congenital CMV infection based on the detection of CMV DNA in his urine and the umbilical cord. After the administration of valganciclovir, no CMV DNA was detected in his serum, and brain MRI and electroencephalogram findings, motor development, and deafness improved. Further investigation is needed to establish a screening test and treatment for congenital CMV infection in Japan. PMID:22352032

  5. Cytomegalovirus (CMV) and Congenital CMV Infection: Transmission

    MedlinePlus

    ... Good Hand Hygiene CDC Feature on Prenatal Infections Transmission Language: English Español (Spanish) Recommend on Facebook Tweet ... should consult their healthcare providers about breastfeeding. CMV Transmission during Pregnancy In the United States, approximately 30- ...

  6. Human Cytomegalovirus Infection Upregulates the Mitochondrial Transcription and Translation Machineries

    PubMed Central

    Weekes, M. P.; Antrobus, R.; Rorbach, J.; van Haute, L.; Umrania, Y.; Smith, D. L.; Minczuk, M.; Lehner, P. J.; Sinclair, J. H.

    2016-01-01

    ABSTRACT Infection with human cytomegalovirus (HCMV) profoundly affects cellular metabolism. Like in tumor cells, HCMV infection increases glycolysis, and glucose carbon is shifted from the mitochondrial tricarboxylic acid cycle to the biosynthesis of fatty acids. However, unlike in many tumor cells, where aerobic glycolysis is accompanied by suppression of mitochondrial oxidative phosphorylation, HCMV induces mitochondrial biogenesis and respiration. Here, we affinity purified mitochondria and used quantitative mass spectrometry to determine how the mitochondrial proteome changes upon HCMV infection. We found that the mitochondrial transcription and translation systems are induced early during the viral replication cycle. Specifically, proteins involved in biogenesis of the mitochondrial ribosome were highly upregulated by HCMV infection. Inhibition of mitochondrial translation with chloramphenicol or knockdown of HCMV-induced ribosome biogenesis factor MRM3 abolished the HCMV-mediated increase in mitochondrially encoded proteins and significantly impaired viral growth under bioenergetically restricting conditions. Our findings demonstrate how HCMV manipulates mitochondrial biogenesis to support its replication. PMID:27025248

  7. Intraperitoneal administration of cytomegalovirus hyperimmunoglobulin to the cytomegalovirus-infected fetus.

    PubMed

    Negishi, H; Yamada, H; Hirayama, E; Okuyama, K; Sagawa, T; Matsumoto, Y; Fujimoto, S

    1998-01-01

    Twenty-five percent of cytomegalovirus (CMV)-infected fetuses had sequelae and 8% of those in the recurrent-infected group had sequelae. There is no report yet on the fetal therapy for CMV infections. A Japanese pregnant woman with intrauterine fetal CMV infection diagnosed at 26 weeks of pregnancy is presented. CMV culture of amniotic fluid was positive. A CMV DNA assay using the polymerase chain reaction method of the cord blood and the amniotic fluid was positive during the pregnancy; however, testing for fetal serum CMV-specific IgM was negative. The CMV IgG titer of fetal serum at 27 weeks of pregnancy was a third of that of the maternal serum. CMV hyperimmunoglobulin was injected into the fetal abdominal cavity at 28 and 29 weeks of pregnancy. A second administration of CMV hyperimmunoglobulin increased the titer of CMV IgG in the fetal circulation. At birth, the urine culture was positive for CMV. However, CMV DNA of the ascites became negative. A brain CT scan performed 2 weeks after birth revealed some small calcifications beside the right ventricle. CMV hyperimmunoglobulin injection to the fetal abdominal cavity has been shown to increase the IgG in the fetal serum. This is the first report of fetal therapy of congenital CMV infection. PMID:9848763

  8. Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus.

    PubMed

    Cocita, Clément; Guiton, Rachel; Bessou, Gilles; Chasson, Lionel; Boyron, Marilyn; Crozat, Karine; Dalod, Marc

    2015-05-01

    In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely

  9. Acute Cytomegalovirus Infection as a Cause of Venous Thromboembolism

    PubMed Central

    Rinaldi, Francesca; Lissandrin, Raffaella; Mojoli, Francesco; Baldanti, Fausto; Brunetti, Enrico; Pascarella, Michela; Giordani, Maria Teresa

    2014-01-01

    Acute Human Cytomegalovirus (HCMV) infection is an unusual cause of venous thromboembolism, a potentially life-threatening condition. Thrombus formation can occur at the onset of the disease or later during the recovery and may also occur in the absence of acute HCMV hepatitis. It is likely due to both vascular endothelium damage caused by HCMV and impairment of the clotting balance caused by the virus itself. Here we report on two immunocompetent women with splanchnic thrombosis that occurred during the course of acute HCMV infection. Although the prevalence of venous thrombosis in patients with acute HCMV infection is unknown, physicians should be aware of its occurrence, particularly in immunocompetent patients presenting with fever and unexplained abdominal pain. PMID:24959338

  10. Natural Killer Cell Evasion Is Essential for Infection by Rhesus Cytomegalovirus.

    PubMed

    Sturgill, Elizabeth R; Malouli, Daniel; Hansen, Scott G; Burwitz, Benjamin J; Seo, Seongkyung; Schneider, Christine L; Womack, Jennie L; Verweij, Marieke C; Ventura, Abigail B; Bhusari, Amruta; Jeffries, Krystal M; Legasse, Alfred W; Axthelm, Michael K; Hudson, Amy W; Sacha, Jonah B; Picker, Louis J; Früh, Klaus

    2016-08-01

    The natural killer cell receptor NKG2D activates NK cells by engaging one of several ligands (NKG2DLs) belonging to either the MIC or ULBP families. Human cytomegalovirus (HCMV) UL16 and UL142 counteract this activation by retaining NKG2DLs and US18 and US20 act via lysomal degradation but the importance of NK cell evasion for infection is unknown. Since NKG2DLs are highly conserved in rhesus macaques, we characterized how NKG2DL interception by rhesus cytomegalovirus (RhCMV) impacts infection in vivo. Interestingly, RhCMV lacks homologs of UL16 and UL142 but instead employs Rh159, the homolog of UL148, to prevent NKG2DL surface expression. Rh159 resides in the endoplasmic reticulum and retains several NKG2DLs whereas UL148 does not interfere with NKG2DL expression. Deletion of Rh159 releases human and rhesus MIC proteins, but not ULBPs, from retention while increasing NK cell stimulation by infected cells. Importantly, RhCMV lacking Rh159 cannot infect CMV-naïve animals unless CD8+ cells, including NK cells, are depleted. However, infection can be rescued by replacing Rh159 with HCMV UL16 suggesting that Rh159 and UL16 perform similar functions in vivo. We therefore conclude that cytomegaloviral interference with NK cell activation is essential to establish but not to maintain chronic infection. PMID:27580123

  11. Acute ulcerative proctocolitis associated with primary cytomegalovirus infection.

    PubMed

    Diepersloot, R J; Kroes, A C; Visser, W; Jiwa, N M; Rothbarth, P H

    1990-08-01

    The case is reported of a 39-year-old pregnant woman who presented with fever, abdominal complaints, and diarrhea. Laboratory investigation revealed mononucleosis in the peripheral blood. All microbiological studies were negative, with the exception of finding cytomegalovirus (CMV). Seroconversion was documented; the virus was cultured from urine and subsequently was demonstrated to be present in the inflamed mucosa of the rectum and distal sigmoid, which was found at sigmoidoscopy. This woman was delivered of a neonate with congenital CMV infection but without apparent malformations. The patient experienced recurrences of the bowel disease, in the first of which CMV could still be cultured from a biopsy specimen. In the follow-up period, an otherwise aspecific chronic inflammatory bowel disease remained present. No immunological abnormalities were found, and antibodies to human immunodeficiency virus were negative. This case demonstrates that inflammatory bowel disease can develop as a result of primary infection with CMV. PMID:2166491

  12. Cutaneous Co-infected Cytomegalovirus and Herpes Simplex Virus Perigenital Ulcers in Human Immunodeficiency Virus Patients.

    PubMed

    Schoenfeld, Jason; Cannon, Sarah; Cam, Kristin; Keller, Matthew

    2013-10-01

    There is uncertainty regarding the pathogenic nature of cytomegalovirus in cutaneous lesions co-infected with herpes simplex virus. It is widely believed that herpes simplex virus is the main pathogenic factor in such lesions and that cytomegalovirus plays little if any role. There are, however, isolated case reports that describe cytomegalovirus as an important driving pathogen in such lesions. The authors present two human immunodeficiency virus patients who have cytomegalovirus and herpes simplex virus co-infected perigenital ulcers, one of whom improved on valacyclovir, while the other, who was already on valacyclovir for chronic herpes simplex virus suppression, showed no improvement with a single dose of cidofovir. He only showed rapid improvement when treated with valganciclovir. The latter patient underscores the viewpoint that at least in some cases, cytomegalovirus may be an important driving force behind the formation of such lesions. The authors therefore recommend that clinicians be aware of the possible pathogenic role of cytomegalovirus in these ulcers, and, in nonhealing ulcers, use anti-cytomegalovirus agents to prevent the onset of systemic disease. These results warrant further study of the pathogenesis of cytomegalovirus in co-infected herpes simplex virus ulcers. PMID:24155993

  13. Intrauterine diagnosis of cytomegalovirus and rubella infections by amniocentesis.

    PubMed Central

    Skvorc-Ranko, R; Lavoie, H; St-Denis, P; Villeneuve, R; Gagnon, M; Chicoine, R; Boucher, M; Guimond, J; Dontigny, Y

    1991-01-01

    OBJECTIVE: To establish a correlation between the presence of cytomegalovirus (CMV) or rubella virus in amniotic fluid obtained through amniocentesis and fetal infection. DESIGN: Case series. SETTING: Five hospitals in the Montreal region. Virology testing was done at the Virology Research Centre, Institut Armand-Frappier, Laval, Que. PATIENTS: Thirteen pregnant women infected with CMV, 3 with rubella, their 15 babies and 2 fetuses. Twelve of the women with CMV infection were recruited from a prospective study of CMV infection in pregnancy. Infection in the other women was detected through routine laboratory diagnostic testing. INTERVENTION: Amniotic fluid samples were cultured for CMV and rubella virus. Congenital infection of the neonates was established through isolation of either virus from pharyngeal mucus and urine specimens collected during the first 3 days of life or from fetal tissue if the pregnancy was terminated. MAIN RESULTS: CMV was cultured from the amniotic fluid of three of the CMV-infected women and from the pharyngeal mucus and urine specimens of their infants. Of the three women with rubella the amniotic fluid of one (who had a twin pregnancy) was positive for rubella virus. After the in-utero death of one fetus she underwent a therapeutic abortion of both. Examination of fetal tissue indicated that both fetuses had been infected with rubella virus. Each of the two other women with rubella gave birth to an uninfected, healthy infant. CONCLUSIONS: We found a strong correlation between the isolation of CMV or rubella virus from the amniotic fluid and the presence of congenital infection. This suggests that amniocentesis used to detect the presence of a virus is a useful method for the diagnosis of fetal infection. PMID:1654193

  14. Cytomegalovirus infection following liver transplantation: review of the literature.

    PubMed

    Kanj, S S; Sharara, A I; Clavien, P A; Hamilton, J D

    1996-03-01

    Cytomegalovirus (CMV) remains a major cause of problems following solid organ transplantation, accounting for a significant increase in morbidity and affiliated costs. Infection with CMV following orthotopic liver transplantation (OLT) is commonly seen as a result of marked cell-mediated immunosuppression and is an independent risk factor for opportunistic and fungal infections. The role of CMV infection in acute cellular or chronic rejection remains unclear. Recent advances in diagnostic modalities, particularly the use of the antigenemia assay and the polymerase chain reaction, have provided ways to quantitate viral load during infection or disease, as well as providing a useful marker of response to therapy. Ganciclovir remains the best antiviral agent for the treatment of CMV disease, but the use of combination therapy with other antivirals or CMV immunoglobulin may improve outcome for patients with severe disease. The ideal prophylactic therapy for patients undergoing OLT remains to be identified, as tested regimens have shown variable efficacy when analyzed with regard to defined risk groups. The use of risk group-specific prophylaxis may prove to be most successful, however, in terms of efficacy and cost savings. Future advances in basic CMV virology and transplant immunology will be essential in defining rational approaches to control and prevention of CMV infection and disease following liver transplantation. PMID:8852975

  15. Human fetal inner ear involvement in congenital cytomegalovirus infection

    PubMed Central

    2013-01-01

    Background Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss (SNHL). The mechanisms of pathogenesis of CMV-related SNHL are still unclear. The aim is to study congenital CMV-related damage in the fetal inner ear, in order to better understand the underlying pathophysiology behind CMV-SNHL. Results We studied inner ears and brains of 20 human fetuses, all at 21 week gestational age, with a high viral load in the amniotic fluid, with and without ultrasound (US) brain abnormalities. We evaluated histological brain damage, inner ear infection, local inflammatory response and tissue viral load. Immunohistochemistry revealed that CMV was positive in 14/20 brains (70%) and in the inner ears of 9/20 fetuses (45%). In the cases with inner ear infection, the marginal cell layer of the stria vascularis was always infected, followed by infection in the Reissner’s membrane. The highest tissue viral load was observed in the inner ear with infected Organ of Corti. Vestibular labyrinth showed CMV infection of sensory cells in the utricle and in the crista ampullaris. US cerebral anomalies were detected in 6 cases, and in all those cases, the inner ear was always involved. In the other 14 cases with normal brain scan, histological brain damage was present in 8 fetuses and 3 of them presented inner ear infection. Conclusions CMV-infection of the marginal cell layer of the stria vascularis may alter potassium and ion circulation, dissipating the endocochlear potential with consequent SNHL. Although abnormal cerebral US is highly predictive of brain and inner ear damage, normal US findings cannot exclude them either. PMID:24252374

  16. Cytomegalovirus infection in the bone marrow transplant patient

    PubMed Central

    Bhat, Vivek; Joshi, Amit; Sarode, Rahul; Chavan, Preeti

    2015-01-01

    Cytomegalovirus (CMV) infection is an important contributor to the morbidity and mortality associated with bone marrow transplantation (BMT). Infection may lead to CMV disease involving multiple organs such as pneumonia, gastroenteritis, retinitis, central nervus system involvement and others. CMV seropositivity is an important risk factor and approximately half of BMT recipients will develop clinically significant infection most commonly in the first 100 d post-transplant. The commonly used tests to diagnose CMV infection in these patients include the pp65 antigenemia test and the CMV DNA polymerase chain reaction (PCR) assay. Because of its greater sensitivity and lesser turnaround time, the CMV PCR is nowadays the preferred test and serves as a main guide for pre-emptive therapy. Methods of CMV prevention include use of blood products from seronegative donors or leukodepleted products. Prophylaxis or pre-emptive therapy strategies for CMV prevention may be used post-transplant with the latter becoming more common. The commonly used antivirals for pre-emptive therapy and CMV disease management include intravenous gancyclovir and foscarnet. The role of intravenous immunoglobulin, although used commonly in CMV pneumonia is not clear. PMID:26722656

  17. Cytomegalovirus infection in immunosuppressed patients after kidney transplantation

    PubMed Central

    LUSCALOV, SIMONA; LOGA, LUMINITA; DICAN, LUCIA; JUNIE, LIA MONICA

    2016-01-01

    The first kidney transplantation was performed in 1951 and ever since then living donor transplantation became a more and more important solution for patients with end-stage renal disease (ESRD). Renal transplantation is a life-saving procedure. Morbidity and mortality on waiting-lists are strongly correlated with the time of dialysis and end-stage renal disease is one of the most important causes of death; this is the reason why transplantation has to be performed as soon as possible in order to reduce the time of dialysis. Once the transplantation is performed, a number of complications may occur in post-transplant evolution, the most important of which is rejection. The rejection may appear through several mechanisms, but one of the most frequent causes of rejection is cytomegalovirus (CMV) infection. It is very important to have a precocious and fast diagnosis of CMV infection in order to maintain the functionality and survival of the graft. PP65 CMV antigenemia has proven its effectiveness in detecting and monitoring the CMV infection in transplanted patients. In the laboratory of the Clinical Institute of Urology and Renal Transplantation (ICUTR) of Cluj Napoca the CMV infection is evidenced by two methods: PP65antigenemia and IgM antibody identification by chemiluminiscence. PMID:27547053

  18. Distribution of Cytomegalovirus Genotypes among Neonates Born to Infected Mothers in Islamabad, Pakistan

    PubMed Central

    Mujtaba, Ghulam; Khurshid, Adnan; Sharif, Salmaan; Alam, Muhammad Masroor; Aamir, Uzma Bashir; Shaukat, Shahzad; Angez, Mehar; Rana, Muhammad Suleman; Umair, Massab; Shah, Aamer Ali; Zaidi, Syed Sohail Zahoor

    2016-01-01

    Background Congenital cytomegalovirus (cCMV) infection contributes to considerable long-term sequelae in neonates and children all over the world. The association between viral genotypes and severity of clinical cytomegalovirus (CMV) infection is yet to be defined. The objective of this study was to find the impact of active CMV infection during pregnancy and the clinical significance of genotypes in neonates with congenital cytomegalovirus infections in Pakistan. Methods A total of 409 blood samples from pregnant women seeking health care services at the two antenatal hospitals of Islamabad during January to December 2012 were tested by ELISA and nested-PCR. Pregnant women with active infection (detected as IgM positive, PCR positive or positive on both assays) were followed until delivery, to detect the outcome of overt cCMV infection in neonates. Genetic characterization of CMV strains was performed by sequence analysis of envelope glycoproteins: gB, gN and gH to detect the contributing CMV genotypes. Results The seroprevalence of anti-CMV IgG and IgM was 97.5% (399 out of 409) and 12.7% (52 out of 409), respectively, while 20% (82/409) pregnant women were found positive for CMV DNA by PCR. Logistic regression analysis showed a significant association of active infection with parity [OR = 2.56, 95% CI = 1.82–2.62, p = 0.04], febrile illness [OR = 1.84, 95% CI = 1.76–3.65, p = 0.01] and jaundice [OR = 22.5, 95% CI = 4.53–85.02, p = 0.002]. We were able to isolate virus in 41 out of 70 neonates; 36.6% (15 out of 41) of them were symptomatic at birth while 63.4% (26 out of 41) were asymptomatic. The most prominent clinical feature observed in symptomatic neonates was hepatosplenomegaly (26.6%; 4 out of 15). All three genotypes gB, gN and gH were found with the highest frequency of gB1 genotype, found in 75% infants with hepatic damage. Phylogenetic analysis of Pakistani strains showed 96%-100% homology to their prototype strains. Conclusions Active CMV

  19. Human Leukocyte Antigen Alleles and Cytomegalovirus Infection After Renal Transplantation

    PubMed Central

    Futohi, Farzaneh; Saber, Azadeh; Nemati, Eglim; Einollahi, Behzad; Rostami, Zohre

    2015-01-01

    Background: Several studies have been conducted on the relationship between a number of human leukocyte antigen (HLA) alleles and cytomegalovirus infection (CMV), in kidney transplant recipients, after transplantation. However, only a limited number of HLAs have been investigated, so far, and the results have been contradictory. Objectives: This study aimed to investigate the relationship between 59 HLA alleles and the CMV infection, in transplant recipients, after kidney transplantation. Patients and Methods: This retrospective cohort study was conducted on 200 patients, receiving a kidney transplant, in Baqiyatallah Hospital, in Tehran, during 2013. Throughout a one-year follow-up of kidney transplant recipients, in case of detecting the CMV antigen in patients’ blood, at any time, they were placed in the group of patients with CMV infection, whereas, if no CMV-specific antigen was developed, over a year, patients were placed in the group of patients without CMV infection, after transplantation. This study investigated the relationship between CMV infection in kidney transplant recipients and 59 HLA alleles, including 14 HLA-A, 28 HLA-B, and 17 HLA-DRB1 cases. Results: Of all participants, 104 patients (52%) were diagnosed with CMV infection. There was no significant difference between the two groups, with and without CMV infection, in terms of patient’s characteristics. The CMV infection, in patients receiving a transplanted organ from deceased donor, was significantly more prevalent than in those receiving kidney transplant from living donor (63% vs. 39%, respectively, P = 0.001). Recipients with HLA-B44 were more infected with CMV compared with patients without this allele (80% vs. 50%, respectively, P = 0.024); on the contrary, kidney recipients with HLA-DRB1-1 were less infected with CMV than patients without this allele (31% vs. 55%, respectively, P = 0.020). There was no significant relationship between CMV infection and other HLA alleles. Results of

  20. Absence of human cytomegalovirus infection in childhood brain tumors.

    PubMed

    Sardi, Iacopo; Lucchesi, Maurizio; Becciani, Sabrina; Facchini, Ludovica; Guidi, Milena; Buccoliero, Anna Maria; Moriondo, Maria; Baroni, Gianna; Stival, Alessia; Farina, Silvia; Genitori, Lorenzo; de Martino, Maurizio

    2015-01-01

    Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients' neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors. PMID:26396923

  1. Absence of human cytomegalovirus infection in childhood brain tumors

    PubMed Central

    Sardi, Iacopo; Lucchesi, Maurizio; Becciani, Sabrina; Facchini, Ludovica; Guidi, Milena; Buccoliero, Anna Maria; Moriondo, Maria; Baroni, Gianna; Stival, Alessia; Farina, Silvia; Genitori, Lorenzo; de Martino, Maurizio

    2015-01-01

    Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients’ neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors. PMID:26396923

  2. Anti-Cytomegalovirus Activity of the Anthraquinone Atanyl Blue PRL

    PubMed Central

    Alam, Zohaib; Al-Mahdi, Zainab; Zhu, Yali; McKee, Zachary; Parris, Deborah S.; Parikh, Hardik I.; Kellogg, Glen E.; Kuchta, Alison; McVoy, Michael A.

    2014-01-01

    Human cytomegalovirus (CMV) causes significant disease in immunocompromised patients and serious birth defects if acquired in utero. Available CMV antivirals target the viral DNA polymerase, have significant toxicities, and suffer from resistance. New drugs targeting different pathways would be beneficial. The anthraquinone emodin is proposed to inhibit herpes simplex virus by blocking the viral nuclease. Emodin and related anthraquinones are also reported to inhibit CMV. In the present study, emodin reduced CMV infectious yield with an EC50 of 4.9 μM but was cytotoxic at concentrations only two-fold higher. Related anthraquinones acid blue 40 and alizarin violet R inhibited CMV at only high concentrations (238–265 μM) that were also cytotoxic. However, atanyl blue PRL inhibited infectious yield of CMV with an EC50 of 6.3 μM, significantly below its 50% cytotoxic concentration of 216 μM. Atanyl blue PRL reduced CMV infectivity and inhibited spread. When added up to one h after infection, it dramatically reduced CMV immediate early protein expression and blocked viral DNA synthesis. However, it had no antiviral activity when added 24 h after infection. Interestingly, atanyl blue PRL inhibited nuclease activities of purified CMV UL98 protein with IC50 of 4.5 and 9.3 μM. These results indicate that atanyl blue PRL targets very early post-entry events in CMV replication and suggest it may act through inhibition of UL98, making it a novel CMV inhibitor. This compound may provide valuable insights into molecular events that occur at the earliest times post-infection and serve as a lead structure for antiviral development. PMID:25499125

  3. High susceptibility to cytomegalovirus infection of pregnant women in Flanders, Belgium

    PubMed Central

    Leuridan, E.; Ieven, M.; Hens, N.; Van Damme, P.

    2012-01-01

    Maternal antibodies against cytomegalovirus (CMV) infection offer, to some extent, protection against congenital CMV infection. This study describes the seroprevalence of CMV-specific IgG in 220 parturient women during pregnancy, at delivery, at 3 months after delivery and in their cord blood (Flanders, Belgium, 2006-2008). ELISA was used to measure IgG. Of this population, 30% had positive IgG titres. Active transplacental transport was confirmed with a ratio 1.15/1. Elevated maternal IgG titre and increased parity, but not age, were significantly associated with higher seroprevalence of CMV-specific IgG in the cord blood. These data indicate a high susceptibility to CMV among fertile women. Prenatal prevention and other strategies to prevent intra-uterine infection are of critical importance in a highly susceptible population. PMID:24753893

  4. Horizontal In Utero Acquisition of Cytomegalovirus Infection in a Twin Pregnancy

    PubMed Central

    Gabrielli, Liliana; Lazzarotto, Tiziana; Foschini, Maria Pia; Lanari, Marcello; Guerra, Brunella; Eusebi, Vincenzo; Landini, Maria Paola

    2003-01-01

    It is generally accepted that viral infections can be transmitted horizontally by direct or indirect contact with virus-excreting persons, and some viral infections can be transmitted vertically, either prenatally or perinatally, from mother to child. This report presents data strongly supporting a prenatal horizontal acquisition of human cytomegalovirus infection in a twin pregnancy. PMID:12624079

  5. Activation of Cytomegalovirus in Pig-to-Primate Organ Xenotransplantation

    PubMed Central

    Mueller, Nicolas J.; Barth, Rolf N.; Yamamoto, Shin; Kitamura, Hiroshi; Patience, Clive; Yamada, Kazuhiko; Cooper, David K. C.; Sachs, David H.; Kaur, Amitinder; Fishman, Jay A.

    2002-01-01

    Xenotransplantation of porcine organs carries the risk of reactivation of latent virus in donor and recipient tissues as well as transmission of viruses between species. We have investigated the activation of baboon cytomegalovirus (BCMV) and porcine CMV (PCMV) in a pig-to-primate model of xenotransplantation. Tissues originating from a series of six swine-to-baboon composite thymokidney xenotransplants were investigated. Four immunosuppressed baboons died (survival range, 7 to 27 days) with the graft in situ. Increases in BCMV DNA copy numbers occurred in three (75%) of these baboons and was thought to be responsible for pneumonitis and the death of one animal. In two baboons, disseminated intravascular coagulation was successfully treated by graftectomy and discontinuation of immunosuppression. PCMV was upregulated in five of six xenografts (83%). PCMV infection was associated with ureteric necrosis in one xenograft. Although significantly increased in native tissues, low levels of BCMV and PCMV were also detected in tissues other than that of the native viral host species. The cross-species presence of CMV did not appear to cause clinical or histological signs of invasive disease. Thus, viral infections with clinical disease were restricted to tissues of the native species of each virus. Intensive immune suppression currently required for xenotransplantation results in a significant risk of reactivation of latent infections by BCMV and PCMV. It is not yet known whether viral DNA detected across species lines represents cellular microchimerism, ongoing viral infection, or uptake of free virus. The observation of graft injury by PCMV demonstrates that CMV will be an important pathogen in immunosuppressed xenograft recipients. Strategies must be developed to exclude CMV from porcine organ donors. PMID:11967290

  6. Two strategies for prevention of cytomegalovirus infections after liver transplantation

    PubMed Central

    Simon, Philipp; Sasse, Max; Laudi, Sven; Petroff, David; Bartels, Michael; Kaisers, Udo X; Bercker, Sven

    2016-01-01

    AIM: To analyze differences in patients’ clinical course, we compared two regimes of either preemptive therapy or prophylaxis after liver transplantation. METHODS: This retrospective study was reviewed and approved by the institutional review board of the University of Leipzig. Cytomegalovirus (CMV) prophylaxis with valganciclovir hydrochloride for liver transplant recipients was replaced by a preemptive strategy in October 2009. We retrospectively compared liver transplant recipients 2 years before and after October 2009. During the first period, all patients received valganciclovir daily. During the second period all patients included in the analysis were treated following a preemptive strategy. Outcomes included one year survival and therapeutic intervention due to CMV viremia or infection. RESULTS: Between 2007 and 2010 n = 226 patients underwent liver transplantation in our center. n = 55 patients were D+/R- high risk recipients and were excluded from further analysis. A further 43 patients had to be excluded since CMV prophylaxis/preemptive strategy was not followed although there was no clinical reason for the deviation. Of the remaining 128 patients whose data were analyzed, 60 received prophylaxis and 68 were treated following a preemptive strategy. The difference in overall mortality was not significant, nor was it significant for one-year mortality where it was 10% (95%CI: 8%-28%, P = 0.31) higher for the preemptive group. No significant differences in blood count abnormalities or the incidence of sepsis and infections were observed other than CMV. In total, 19 patients (14.7%) received ganciclovir due to CMV viremia and/or infections. Patients who were treated according to the preemptive algorithm had a significantly higher rate risk of therapeutic intervention with ganciclovir [n = 16 (23.5%) vs n = 3 (4.9%), P = 0.003)]. CONCLUSION: These data suggest that CMV prophylaxis is superior to a preemptive strategy in patients undergoing liver

  7. Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients

    PubMed Central

    Göhring, Katharina; Hamprecht, Klaus; Jahn, Gerhard

    2015-01-01

    In pediatric and adult patients after stem cell transplantation (SCT) disseminated infections caused by human cytomegalovirus (HCMV) can cause life threatening diseases. For treatment, the three antivirals ganciclovir (GCV), foscarnet (PFA) and cidofovir (CDV) are approved and most frequently used. Resistance to all of these antiviral drugs may induce a severe problem in this patient cohort. Responsible for resistance phenomena are mutations in the HCMV phosphotransferase-gene (UL97) and the polymerase-gene (UL54). Most frequently mutations in the UL97-gene are associated with resistance to GCV. Resistance against all three drugs is associated to mutations in the UL54-gene. Monitoring of drug resistance by genotyping is mostly done by PCR-based Sanger sequencing. For phenotyping with cell culture the isolation of HCMV is a prerequisite. The development of multidrug resistance with mutation in both genes is rare, but it is often associated with a fatal outcome. The manifestation of multidrug resistance is mostly associated with combined UL97/UL54-mutations. Normally, mutations in the UL97 gene occur initially followed by UL54 mutation after therapy switch. The appearance of UL54-mutation alone without any detection of UL97-mutation is rare. Interestingly, in a number of patients the UL97 mutation could be detected in specific compartments exclusively and not in blood. PMID:25750703

  8. Effect of acute cytomegalovirus infection on drug-induced SLE.

    PubMed Central

    Schattner, A.; Sthoeger, Z.; Geltner, D.

    1994-01-01

    A 58 year old woman developed systemic symptoms, interstitial lung disease, splenomegaly, leukopenia and anti-histone and anti-nuclear antibodies (ANA), while treated with hydralazine for hypertension. Five months after presentation she was admitted with high fever, skin rash and atypical lymphocytosis due to acute cytomegalovirus (CMV) infection. Worsening leukopenia and increased ANA were found, and high titres of anti-DNA antibodies, anti-cardiolipin antibodies and rheumatoid factors appeared. Hydralazine was stopped and the patient gradually became asymptomatic. All autoantibodies spontaneously disappeared (over 16 weeks), and the white cell count and spleen size became normal. The patient was found to be a slow acetylator and to have both HLA-DR4 and selective IgA deficiency. Thus, a multifactorial genetic susceptibility to develop drug-induced lupus was brought out in stages first by hydralazine and then by CMV, yet all manifestations and autoantibodies resolved spontaneously, demonstrating the complex interplay of varied environmental factors with a genetic predisposition in the pathogenesis of autoimmunity. PMID:7831173

  9. Cytomegalovirus infection in renal transplantation: clinical aspects, management and the perspectives

    PubMed Central

    Requião-Moura, Lúcio Roberto; de Matos, Ana Cristina Carvalho; Pacheco-Silva, Alvaro

    2015-01-01

    Cytomegalovirus infection is one of most frequent infectious complications after renal transplantation, and can be classified as primo-infection, when the transmission occurs through the graft, or reactivation, when the recipient is cytomegalovirus seropositive. After transplantation, cytomegalovirus can appear as an infection, when the patient presents with evidence of viral replication without symptoms or disease, which has two clinical spectra: typical viral syndrome or invasive disease, which is a less common form. Their effects can be classified as direct, while the disease is developed, or indirect, with an increase of acute rejection and chronic allograft dysfunction risks. Diagnosis must be made based on viremia by one of the standardized methods: antigenemia or PCR, which is more sensitive. The risk factors related to infection after transplantation are the serologic matching (positive donor and negative recipient) and anti-lymphocyte antibody drugs. One of the strategies to reduce risk of disease should be chosen for patients at high risk: preemptive treatment or universal prophylaxis. Recent clinical research has described ganciclovir resistance as an emergent problem in management of cytomegalovirus infection. Two types of mutation that cause resistance were described: UL97 (most frequent) and UL54. Today, sophisticated methods of immunologic monitoring to detect specific T-cell clones against cytomegalovirus are used in clinical practice to improve the management of high-risk patients after renal transplantation. PMID:25993081

  10. Immunological response to cytomegalovirus in congenitally infected neonates

    PubMed Central

    Hassan, J; Dooley, S; Hall, W

    2007-01-01

    Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide and occurs as a result of transplacental transmission of the virus. The human neonate is highly susceptible to infection due to a combination of immaturity of the immune system and antigenic inexperience. This study uses the in vivo model of congenital CMV to examine both the humoral and cell-mediated immune responses in vertically infected neonates and their mothers. Ten pairs of matched neonates and their mothers were evaluated for specific IgM responses to three immunodominant CMV antigens: pp38 (pUL80a), pp52 (pUL44) and pp150 (pUL32). In contrast to conventional enzyme immunoassay (EIA) testing for CMV-specific IgM, which found five of the mothers and four of the neonates to be positive, Western immunoblotting showed all 10 adults and nine newborns to be positive. Eight mothers and nine newborns had serological evidence of primary infection. All neonates showed a response to pp38, an assembly protein, nine responded to the pp52 immediate early antigen but only four had reactivity to the pp150 tegument associated protein. Of the mothers, eight had pp38 reactivity, 10 showed a response to the pp52 antigen and seven to the pp150 antigen. T cell-mediated immunity was assessed by measuring cytokines using a multiplex microarray assay. Levels of interferon (IFN)-γ were high in both groups [mean ± standard error of the mean (s.e.m.): neonates = 657 ± 238 pg/ml, mothers = 1072 ± 677 pg/ml, pNS]; however, neonates had significantly higher levels of interleukin (IL)-8 (316 ± 136 pg/ml versus 48 ± 28 pg/ml, P < 0·005). Similar levels of IL-2, IL-7, IL-10 and IL-12 were measured in both groups, but levels of IL-1α, IL-1β, IL-4, IL-6 and tumour necrosis factor (TNF)-α were either absent or low. In response to CMV, neonates and adults mount a predominant T helper 1 (Th1) response, as evidenced by the presence of IL-2, IL-8, IL-12 and IFN-γ with concomitant lack of IL-4. These

  11. [Ulcerous colitis and infection with cytomegalovirus, herpes simplex virus and clostridium difficile].

    PubMed

    Arnold, C; von Sanden, S; Theilacker, C; Blum, H E

    2008-08-01

    The treatment of severe flares of ulcerative colitis is based on systemic corticosteroids, immunomodulators such as cyclosporine and azathioprine and in some cases TNF-alpha-antagonists, respectively. These immunosuppressed patients are susceptible for infectious pathogens. Here we report the case of a patient with a severe flare of ulcerative colitis that was first treated with systemic corticosteroids combined with immunomodulators and subsequent with infliximab. The patient then experienced an infection with Clostridium difficile and cytomegalovirus of the colon and a Herpes simplex esophagitis, respectively. After specific treatment the patient responded well to the immunosuppressive therapy. This case illustrates that infections have to be considered before systemic treatment of an acute flare of ulcerative colitis is instituted especially in the case of disease activation during immunosuppressive treatment. PMID:18759202

  12. Cytomegalovirus Infection Drives Adaptive Epigenetic Diversification of NK Cells with Altered Signaling and Effector Function

    PubMed Central

    Schlums, Heinrich; Cichocki, Frank; Tesi, Bianca; Theorell, Jakob; Beziat, Vivien; Holmes, Tim D.; Han, Hongya; Chiang, Samuel C.C.; Foley, Bree; Mattsson, Kristin; Larsson, Stella; Schaffer, Marie; Malmberg, Karl-Johan; Ljunggren, Hans-Gustaf; Miller, Jeffrey S.; Bryceson, Yenan T.

    2015-01-01

    SUMMARY The mechanisms underlying human natural killer (NK) cell phenotypic and functional heterogeneity are unknown. Here, we describe the emergence of diverse subsets of human NK cells selectively lacking expression of signaling proteins after human cytomegalovirus (HCMV) infection. The absence of B and myeloid cell-related signaling protein expression in these NK cell subsets correlated with promoter DNA hyperme-thylation. Genome-wide DNA methylation patterns were strikingly similar between HCMV-associated adaptive NK cells and cytotoxic effector T cells but differed from those of canonical NK cells. Functional interrogation demonstrated altered cytokine responsiveness in adaptive NK cells that was linked to reduced expression of the transcription factor PLZF. Furthermore, subsets of adaptive NK cells demonstrated significantly reduced functional responses to activated autologous T cells. The present results uncover a spectrum of epigenetically unique adaptive NK cell subsets that diversify in response to viral infection and have distinct functional capabilities compared to canonical NK cell subsets. PMID:25786176

  13. AABB Committee Report: reducing transfusion-transmitted cytomegalovirus infections.

    PubMed

    Heddle, Nancy M; Boeckh, Michael; Grossman, Brenda; Jacobson, Jessica; Kleinman, Steven; Tobian, Aaron A R; Webert, Kathryn; Wong, Edward C C; Roback, John D

    2016-06-01

    Transfusion-transmitted cytomegalovirus (TT-CMV) is often asymptomatic, but certain patient populations, such as very low birth weight neonates, fetuses requiring intrauterine transfusion, pregnant women, patients with primary immunodeficiencies, transplant recipients, and patients receiving chemotherapy or transplantation for malignant disease, may be at risk of life-threatening CMV infection. It is unclear whether leukoreduction of cellular blood components is sufficient to reduce TT-CMV or whether CMV serological testing adds additional benefit to leukoreduction. The AABB CMV Prevention Work Group commissioned a systematic review to address these issues and subsequently develop clinical practice guidelines. However, the data were of poor quality, and no studies of significant size have been performed for over a decade. Rather than creating guidelines of questionable utility, the Work Group (with approval of the AABB Board of Directors) voted to prepare this Committee Report. There is wide variation in practices of using leukoreduced components alone or combining CMV-serology and leukoreduction to prevent TT-CMV for at-risk patients. Other approaches may also be feasible to prevent TT-CMV, including plasma nucleic acid testing, pathogen inactivation, and patient blood management programs to reduce the frequency of inappropriate transfusions. It is unlikely that future large-scale clinical trials will be performed to determine whether leukoreduction, CMV-serology, or a combination of both is superior. Consequently, alternative strategies including pragmatic randomized controlled trials, registries, and collaborations for electronic data merging, nontraditional approaches to inform evidence, or development of a systematic approach to inform expert opinion may help to address the issue of CMV-safe blood components. PMID:26968400

  14. Co-infection of Plasmodium vivax Malaria and Cytomegalovirus in an Immunocompetent Neonate.

    PubMed

    Chandelia, Sudha; Jain, Sarika

    2014-12-01

    Co-infections when occur can pose substantial diagnostic and treatment challenges for clinicians. In this case report we describe a neonate with co infection of plasmodium vivax malaria with Cytomegalovirus and discuss whether it can be the result of reactivation of one by the other infection postnatally or if these infections can affect and facilitate the transplacental transmission of each other from the mother. PMID:25653999

  15. Vascular dysfunction in young, mid-aged and aged mice with latent cytomegalovirus infections

    PubMed Central

    Gombos, R. B.; Brown, J. C.; Teefy, J.; Gibeault, R. L.; Conn, K. L.; Schang, L. M.

    2013-01-01

    Human cytomegalovirus (HCMV) is associated with vascular diseases in both immunosuppressed and immunocompetent individuals. CMV infections cycle between active and latent phases throughout life. We and others have shown vascular dysfunction during active mouse CMV (mCMV) infections. Few studies have examined changes in physiology during latent CMV infections, particularly vascular responses or whether the negative effects of aging on vascular function and fertility will be exacerbated under these conditions. We measured vascular responses in intact mesenteric and uterine arteries dissected from young, mid-aged, and aged latently mCMV-infected (mCMV genomes are present but infectious virus is undetectable) and age-matched uninfected mice using a pressure myograph. We tested responses to the α1-adrenergic agonist phenylephrine, the nitric oxide donor sodium nitroprusside, and the endothelium-dependent vasodilator methacholine. In young latently mCMV-infected mice, vasoconstriction was increased and vasodilation was decreased in mesenteric arteries, whereas both vasoconstriction and vasodilation were increased in uterine arteries compared with those in age-matched uninfected mice. In reproductively active mid-aged latently infected mice, mesenteric arteries showed little change, whereas uterine arteries showed greatly increased vasoconstriction. These vascular effects may have contributed to the decreased reproductive success observed in mid-aged latently mCMV-infected compared with age-matched uninfected mice (16.7 vs. 46.7%, respectively). In aged latently infected mice, vasodilation is increased in mesenteric and uterine arteries likely to compensate for increased vasoconstriction to mediators other than phenylephrine. The novel results of this study show that even when active mCMV infections become undetectable, vascular dysfunction continues and differs with age and artery origin. PMID:23125213

  16. Cytomegalovirus infection associated with clonal proliferation of T-cell large granular lymphocytes: causal or casual?

    PubMed

    Wong, K F; Yip, S F; So, C C; Lau, G T C; Yeung, Y M

    2003-04-01

    Clonal proliferation of T-cell large granular lymphocytes (LGL) is an indolent disorder characterized by splenomegaly, lymphocytosis and frequent manifestations of immune disturbances. The LGL are CD3(+) CD4(-) CD8(+) CD56(-). The clonality of the tumor cell population is often only demonstrable by T-cell receptor (TCR) gene rearrangement study because chromosomal abnormality is distinctly rare. We describe a case of T-cell LGL leukemia that presented initially as cytomegalovirus infection. The leukemic LGL are shown to be clonal by both TCR gene rearrangement and chromosomal studies. They persist after subsidence of the cytomegalovirus infection. PMID:12660039

  17. Cytomegalovirus infection impairs immunosuppressive and antimicrobial effector functions of human multipotent mesenchymal stromal cells.

    PubMed

    Meisel, Roland; Heseler, Kathrin; Nau, Julia; Schmidt, Silvia Kathrin; Leineweber, Margret; Pudelko, Sabine; Wenning, Johannes; Zimmermann, Albert; Hengel, Hartmut; Sinzger, Christian; Degistirici, Özer; Sorg, Rüdiger Volker; Däubener, Walter

    2014-01-01

    Human mesenchymal stromal cells (MSC) possess immunosuppressive and antimicrobial effects that are partly mediated by the tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). Therefore MSC represent a promising novel cellular immunosuppressant which has the potential to control steroid-refractory acute graft versus host disease (GvHD). In addition, MSC are capable of reducing the risk of infection in patients after haematopoietic stem cell transplantation (HST). Recent data indicate that signals from the microenvironment including those from microbes may modulate MSC effector functions. As Cytomegalovirus (CMV) represents a prominent pathogen in immunocompromised hosts, especially in patients following HST, we investigated the impact of CMV infection on MSC-mediated effects on the immune system. We demonstrate that CMV-infected MSC lose their cytokine-induced immunosuppressive capacity and are no longer able to restrict microbial growth. IDO expression is substantially impaired following CMV infection of MSC and this interaction critically depends on intact virus and the number of MSC as well as the viral load. Since overt CMV infection may undermine the clinical efficacy of MSC in the treatment of GvHD in transplant patients, we recommend that patients scheduled for MSC therapy should undergo thorough evaluation for an active CMV infection and receive CMV-directed antiviral therapy prior to the administration of MSC. PMID:24782599

  18. COMPARISON OF THE PATHOGENESIS OF MURINE CYTOMEGALOVIRUS IN LUNG AND LIVER FOLLOWING INTRAPERITONEAL OR INTRATRACHEAL INFECTION

    EPA Science Inventory

    This study compares the pathogenesis of murine cytomegalovirus (MCMV) infections following intraperitoneal (I.P.) and intratracheal (I.T.) inoculation. No deaths were seen in mice given 1,000,000 pfu MCMV I.T., whereas 52% mortality occurred among animals given this dose I.P. Thi...

  19. INCREASED SUSCEPTIBILITY TO PENTOBARBITAL FOLLOWING MOUSE CYTOMEGALOVIRUS INFECTION: ROLE OF VIRAL-INDUCED INTERFERON

    EPA Science Inventory

    The purpose of this study was to determine the relative roles of viral induced interferon (IFN) and viral infection of the liver in mouse cytomegalovirus (MCMV)-induced depression of cytochrome P-450 (cyt P-450) levels and enhancement of pentobarbital-induced sleeping time (PEN-S...

  20. In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

    SciTech Connect

    Forstrom, L.A.; Loken, M.K.; Cook, A.; Chandler, R.; McCullough, J.

    1981-04-01

    Indium-111-labelled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labelling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111 leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients.

  1. In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

    SciTech Connect

    Forstrom, L.A.; Loken, M.K.; Cook, A.; Chandler, R.; McCullough, J.

    1981-04-01

    Indium-111-labeled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labeling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111-leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients.

  2. A Supraglottic Pseudotumor in an Immunocompromised Patient with Nephrotic Syndrome, Herpes Zoster, and a Cytomegalovirus Infection

    PubMed Central

    Akimoto, Tetsu; Yamazaki, Tomoyuki; Saito, Osamu; Muto, Shigeaki; Kusano, Eiji; Nagata, Daisuke

    2016-01-01

    Several viral infections may occasionally induce supraglottic mass lesions, resulting in an obstructive airway emergency. We herein report one such case in a 63-year-old male immunocompromised patient with nephrotic syndrome due to membranous nephropathy who also had ophthalmic herpes zoster with a laryngeal mass, which required urgent intubation and mechanical ventilation. The patient was initially treated with acyclovir; however, because a serological analysis revealed a concurrent cytomegalovirus infection, we discontinued the administration of acyclovir and gave priority to the simultaneous treatment of the cytomegalovirus and varicella-zoster virus infections with ganciclovir. The clinical course was favorable, and he was weaned from the ventilator 10 days later when a serial imaging analysis revealed no signs of the supraglottic mass, leading us to conclude that these two viral infections could have additively or synergistically contributed to the development of the local pseudotumor. The diagnostic and therapeutic concerns arising in the current case are also discussed. PMID:27547043

  3. [Severe thrombocytopenia associated with simultaneous cytomegalovirus and Epstein-barr virus infection in an immunocompetence patient].

    PubMed

    Bober, Grazyna; Krawczyk-Kuliś, Małgorzata; Kopera, Małgorzata; Hołowiecki, Jerzy

    2003-06-01

    A 22 year old woman, without preceeding immunological and hematological disorders was hospitalized because of severe thrombocytopenia. The results of extended workup revealed simultaneous cytomegalovirus and Epstein-Barr virus infection as the most probable causative factor. Both, thrombocytopenia and the symptoms of viral infections resolved after consequent treatment with acyclovir, corticosteroids and intravenous immunoglobulines. Based on this original case report authors suggest the need of virological tests in newly diagnosed idiopatic thrombocytopenia. PMID:14567095

  4. In vitro activity evaluation of Parkia pendula seed lectin against human cytomegalovirus and herpes virus 6.

    PubMed

    Favacho, Alexsandra R M; Cintra, Elizabete A; Coelho, Luana C B B; Linhares, Maria Iêda S

    2007-06-01

    Human cytomegalovirus (HCMV) in vitro infectivity was inhibited by Parkia pendula seed lectin (PpeL) in contrast to human herpes virus 6 (HHV-6) which was not affected. The antiviral activity was detected for HCMV in human embryo lung (HEL) cells using a microtechnique in culture plates. The assay showed a reduction of cellular infectivity from approximately 95%, at a concentration of 150microg/mL with minimal cytotoxicity (25%). Also, a reduction of 75% was observed in HEL cells at a concentration of 75microg/mL without toxic effect. The reduction on infectivity was observed even after virus pre-adsorption to cells suggesting that this action should occur after virus penetration, in the intracellular replication phase. MT4 lymphocytes and cord blood mononuclear cells (CBMC) were used to evaluate the lectin effect on HHV-6 following the same technique. Lectin concentrations with few or no toxic effects on lymphocytes did not show inhibitory action of HHV-6 cytopathic effect. The results obtained with PpeL demonstrate that it may have an impact in the design of pharmacological strategies to infection of cytomegalovirus. PMID:17254798

  5. A High-Affinity Native Human Antibody Neutralizes Human Cytomegalovirus Infection of Diverse Cell Types

    PubMed Central

    Liu, Keyi; Park, Minha; DeChene, Neal; Stephenson, Robert; Tenorio, Edgar; Ellsworth, Stote L.; Tabata, Takako; Petitt, Matthew; Tsuge, Mitsuru; Fang-Hoover, June; Adler, Stuart P.; Cui, Xiaohong; McVoy, Michael A.; Pereira, Lenore

    2014-01-01

    Human cytomegalovirus (HCMV) is the most common infection causing poor outcomes among transplant recipients. Maternal infection and transplacental transmission are major causes of permanent birth defects. Although no active vaccines to prevent HCMV infection have been approved, passive immunization with HCMV-specific immunoglobulin has shown promise in the treatment of both transplant and congenital indications. Antibodies targeting the viral glycoprotein B (gB) surface protein are known to neutralize HCMV infectivity, with high-affinity binding being a desirable trait, both to compete with low-affinity antibodies that promote the transmission of virus across the placenta and to displace nonneutralizing antibodies binding nearby epitopes. Using a miniaturized screening technology to characterize secreted IgG from single human B lymphocytes, 30 antibodies directed against gB were previously cloned. The most potent clone, TRL345, is described here. Its measured affinity was 1 pM for the highly conserved site I of the AD-2 epitope of gB. Strain-independent neutralization was confirmed for 15 primary HCMV clinical isolates. TRL345 prevented HCMV infection of placental fibroblasts, smooth muscle cells, endothelial cells, and epithelial cells, and it inhibited postinfection HCMV spread in epithelial cells. The potential utility for preventing congenital transmission is supported by the blockage of HCMV infection of placental cell types central to virus transmission to the fetus, including differentiating cytotrophoblasts, trophoblast progenitor cells, and placental fibroblasts. Further, TRL345 was effective at controlling an ex vivo infection of human placental anchoring villi. TRL345 has been utilized on a commercial scale and is a candidate for clinical evaluation. PMID:25534746

  6. Quantitation of cytomegalovirus (CMV) DNA by real-time PCR for occurrence of CMV disease in HIV-infected patients receiving highly active antiretroviral therapy.

    PubMed

    Gourlain, Karine; Salmon, Dominique; Gault, Elyanne; Leport, Catherine; Katlama, Christine; Matheron, Sophie; Costagliola, Dominique; Mazeron, Marie-Christine; Fillet, Anne-Marie

    2003-03-01

    In HIV-infected patients treated with highly active antiretroviral therapy (HAART) included in the Predivir cohort, we have evaluated the usefulness of CMV DNA quantitation by a TaqMan PCR assay from peripheral blood leukocytes (PBLs) to predict CMV disease occurrence. In parallel with the immune restoration after treatment by HAART, the percentage of positive samples decreased progressively from 7.3% at Day 0 to 3.5% at Month 12. Among the CMV markers, the smallest concordance with PBL CMV TaqMan PCR, as evaluated by kappa, was observed with pp65 antigenemia, whereas concordance with all other CMV markers was high. Among the 16 patients with CMV DNA copies at least once >100/150,000 cells, CMV disease occurred in six during follow-up, whereas among the 159 patients with CMV DNA copies always <10/150,000 cells, CMV disease occurred in three and among the seven patients with CMV DNA copies >10 and <100 occurred in only one. In univariate Cox models, all the CMV markers including PBL CMV TaqMan PCR >10/150,000 cells (RR: 27.6, IC95: 7.1-107.2), the CD4 cell count <75 cells/mm(3) and the HIV viral load >100,000 copies/ml were predictive for CMV disease. In a stepwise multivariate analysis, which should be interpreted with caution due to the small number of events (n = 10), three covariates were associated independently with CMV disease: pp65 antigenemia >100 nuclei/200,000, PBL CMV TaqMan PCR >10 copies/150,000 cells and HIV viral load remaining or increasing >100,000 copies/ml. PMID:12526052

  7. Colonic perforation in a patient with systemic lupus erythematosus accompanied by cytomegalovirus infection: A case report

    PubMed Central

    Tachikawa, Yuichi; Nozawa, Hiroaki; Tanaka, Junichiro; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Kazama, Shinsuke; Yamaguchi, Hironori; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Fujisawa, Madoka; Takahashi, Katutoshi; Sakaguchi, Yoshiki; Ushiku, Tetsuo; Fukayama, Masashi; Watanabe, Toshiaki

    2016-01-01

    Introduction Cytomegalovirus (CMV) infection of the gastrointestinal tract is an uncommon illness, but can be observed in immunocompromised patients. Systemic lupus erythematosus (SLE) patients are generally at high risk of CMV infection. Here we report a subacute progressive case of colitis in SLE accompanied by cytomegalovirus infection. Presentation of case The patient, a 79-year-old woman, was hospitalized complaining of fever, polyarthritis, and skin ulcer that had lasted seven days. She additionally manifested vomiting, high fever, and right abdominal pain within two weeks thereafter, and was diagnosed with perforation of the intestine. Emergency operation was carried out for panperitonitis due to perforation of one of the multiple colon ulcers. Multidisciplinary postoperative treatment could not save her life. Pathological examination suggested that cytomegalovirus infection as well as cholesterin embolization contributed to the rapid progression of colitis. Discussion There have been only a limited number of case reports of CMV enteritis in SLE. Moreover, only two SLE patients on multiple medications have been reported to experience gastrointestinal perforation. Viral infections, including CMV, can induce clinical manifestations resembling SLE and for this reason we suspect that there are potentially many more patients misdiagnosed and/or unreported. Conclusion Our case underscores the importance of exploring the possibility of CMV infection as a differential diagnosis in SLE patients with obvious gastrointestinal symptoms who were treated by immunosuppressive drugs. PMID:27093690

  8. Intrinsic Contribution of Perforin to NK-Cell Homeostasis during Mouse Cytomegalovirus Infection

    PubMed Central

    Arapović, Maja; Brizić, Ilija; Popović, Branka; Jurković, Slaven; Jordan, Stefan; Krmpotić, Astrid; Arapović, Jurica; Jonjić, Stipan

    2016-01-01

    In addition to their role as effector cells in virus control, natural killer (NK) cells have an immunoregulatory function in shaping the antiviral T-cell response. This function is further pronounced in perforin-deficient mice that show the enhanced NK-cell proliferation and cytokine secretion upon mouse cytomegalovirus (MCMV) infection. Here, we confirmed that stronger activation and maturation of NK cells in perforin-deficient mice correlates with higher MCMV load. To further characterize the immunoregulatory potential of perforin, we compared the response of NK cells that express or do not express perforin using bone-marrow chimeras. Our results demonstrated that the enhanced proliferation and maturation of NK cells in MCMV-infected bone-marrow chimeras is an intrinsic property of perforin-deficient NK cells. Thus, in addition to confirming that NK-cell proliferation is virus load dependent, our data extend this notion demonstrating that perforin plays an intrinsic role as a feedback mechanism in the regulation of NK-cell proliferation during viral infections. PMID:27092144

  9. Intrinsic Contribution of Perforin to NK-Cell Homeostasis during Mouse Cytomegalovirus Infection.

    PubMed

    Arapović, Maja; Brizić, Ilija; Popović, Branka; Jurković, Slaven; Jordan, Stefan; Krmpotić, Astrid; Arapović, Jurica; Jonjić, Stipan

    2016-01-01

    In addition to their role as effector cells in virus control, natural killer (NK) cells have an immunoregulatory function in shaping the antiviral T-cell response. This function is further pronounced in perforin-deficient mice that show the enhanced NK-cell proliferation and cytokine secretion upon mouse cytomegalovirus (MCMV) infection. Here, we confirmed that stronger activation and maturation of NK cells in perforin-deficient mice correlates with higher MCMV load. To further characterize the immunoregulatory potential of perforin, we compared the response of NK cells that express or do not express perforin using bone-marrow chimeras. Our results demonstrated that the enhanced proliferation and maturation of NK cells in MCMV-infected bone-marrow chimeras is an intrinsic property of perforin-deficient NK cells. Thus, in addition to confirming that NK-cell proliferation is virus load dependent, our data extend this notion demonstrating that perforin plays an intrinsic role as a feedback mechanism in the regulation of NK-cell proliferation during viral infections. PMID:27092144

  10. Molecular dissection of the human B cell response against cytomegalovirus infection by lambda display.

    PubMed

    Beghetto, Elisa; Paolis, Francesca De; Spadoni, Andrea; Del Porto, Paola; Buffolano, Wilma; Gargano, Nicola

    2008-07-01

    Human cytomegalovirus (HCMV), a ubiquitous herpesvirus, is the main cause of congenital abnormalities and mental retardation in newborns and is also responsible for severe life-threatening complications in immunocompromised individuals, including AIDS patients and transplant recipients. The disorders generated by cytomegalovirus are closely associated with the competence of the host immune system and both humoral and cell-mediated mechanisms are involved in the response to viral infection. To identify viral proteins recognized by host antibody responses, a cytomegalovirus genome library was created and displayed on lambda bacteriophage. The challenge of such a library with sera from individuals with congenital or acquired infection allowed the identification of a wide panel of recombinant bacteriophages carrying cytomegalovirus B cell epitopes. Epitope-containing fragments within the families of tegument proteins (pUL25, pUL32), structural proteins (pUL48, pUL56) and glycoproteins (pUL55) were identified. Moreover, library screening permitted isolation of phage clones carrying an antigenic region of an uncharacterized HCMV protein encoded by the UL71 open reading frame (ORF), highlighting the potential of lambda display technology in antigen and epitope discovery. PMID:18499273

  11. Cytomegalovirus infection in a cohort of pregnant women.

    PubMed

    El Sanousi, S M; Osman, Z A; Mohmed, A B S; Al Awfi, M S H

    2016-04-01

    Enzyme linked immunosorbent assay was used to detect the seroprevalence of cytomegalovirus (CMV) immunoglobulin M (IgM) and immunoglobulin G (IgG) in 300 pregnant women. Seventeen (5.7%) and 274 (91.3%) women were seropositive for IgM and IgG, respectively. There was significant increase in seroprevalence of CMV IgG and no significant increase in seroprevalence of CMV IgM among tested age groups. CMV IgM and IgG seroprevalence differed nonsignificantly by type of residence, the stage of pregnancy, and the level of education. PMID:26810886

  12. Characterization of Cytomegalovirus Lung Infection in Non-HIV Infected Children

    PubMed Central

    Restrepo-Gualteros, Sonia M.; Jaramillo-Barberi, Lina E.; Gonzalez-Santos, Monica; Rodriguez-Martinez, Carlos E.; Perez, Geovanny F.; Gutierrez, Maria J.; Nino, Gustavo

    2014-01-01

    Cytomegalovirus (CMV) is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years), using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%), hypoxemia (100%), diffuse adventitious breath sounds (100%) and increased respiratory effort (93%). All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in the lung either by CMV PCR in bronchoalveolar lavage (82% detection rate) or histology/immunohistochemistry in lung biopsy (100% detection rate). CMV caused respiratory failure in 47% of children infected and the overall mortality rate was 13.3%. Conclusion: CMV pneumonia is a potential lethal disease in non-HIV infected children that requires a high-index of suspicion. Common clinical and radiological patterns such as hypoxemia, diffuse adventitious lung sounds and ground-glass pulmonary opacities may allow early identification of CMV lung infection in the pediatric population, which may lead to prompt initiation of antiviral therapy and better clinical outcomes. PMID:24811320

  13. Cytomegalovirus infection in gastrointestinal tracts of patients infected with HIV-1 or AIDS.

    PubMed Central

    Francis, N D; Boylston, A W; Roberts, A H; Parkin, J M; Pinching, A J

    1989-01-01

    All gastrointestinal tract biopsy specimens from 190 patients positive for HIV-1 or with AIDS were reviewed to assess the prevalence of cytomegalovirus (CMV) infection, morphology of infected cells, and the associated histopathological features. Eighteen patients (10 (7.7%) of 129 HIV antibody positive and eight (13.1%) of 61 with AIDS) had CMV identified in 35 biopsy specimens from the following sites: oesophagus (n = 3); stomach (n = 6); small intestine (n = 4); colorectum (n = 18) and perianal area (n = 4). Eleven patients had CMV alone as the potential cause of symptoms and in seven there were coexistent pathogens or Kaposi's sarcoma. The appearance and type of infected cells at different sites was highly variable. Immunocytochemical techniques and electron microscopic examination were performed to confirm the presence of CMV antigen and CMV virus particles and to exclude the possibility of an adenovirus producing similar cytopathic changes. It is important to recognise the different morphological forms of infected cells, and the use of immunocytochemical techniques is recommended in patients at risk for CMV or in whom CMV infection is suspected. Images PMID:2555397

  14. Chromatin structure regulates human cytomegalovirus gene expression during latency, reactivation and lytic infection.

    PubMed

    Sinclair, John

    2010-01-01

    Infection of cells with human cytomegalovirus (HCMV) has two potential outcomes. For instance, infection of fibroblasts results in extensive viral gene expression, viral DNA replication and release of progeny virus. In contrast, in undifferentiated myeloid cells, the lytic transcription programme of HCMV is effectively suppressed and cells undergo latent infection. It is now accepted that the suppression of viral lytic gene expression observed during latency in myeloid cells is a result of the inability of undifferentiated cell types to support robust viral immediate early (IE) gene expression--crucial genes responsible for driving the lytic cycle. The repression of IE gene expression in undifferentiated myeloid cells, at least in part, results from specific post-translational modifications of histones associated with the viral major immediate early promoter (MIEP). In cells of the early myeloid lineage, the histone modifications present on the MIEP impart on it a repressive chromatin structure preventing transcriptional activity. Reactivation of HCMV lytic infection is correlated to changes in histone modifications around the MIEP resulting in a chromatin structure conducive to transcriptional activity. These changes are intimately linked with the differentiation of myeloid cells - a phenomenon known to reactivate latent virus in vivo. Chromatin structure of the viral MIEP, therefore, plays a crucial role in latency and reactivation of this persistent human herpesvirus. Whether chromatin-mediated regulation of viral lytic gene expression also occurs, is only beginning to be addressed. However, recent work suggests that all classes of lytic HCMV promoters are subjected to regulation by post-translational modification of their associated histones throughout the time course of infection. Incoming viral genomes appear to be the targets of intrinsic cellular defence mechanisms which attempt to silence viral gene expression through chromatinisation. Viral functions

  15. Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.

    PubMed

    Avery, R K; Bolwell, B J; Yen-Lieberman, B; Lurain, N; Waldman, W J; Longworth, D L; Taege, A J; Mossad, S B; Kohn, D; Long, J R; Curtis, J; Kalaycio, M; Pohlman, B; Williams, J W

    2004-12-01

    Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined. PMID:15489872

  16. [Diagnosis of congenital cytomegalovirus infection in newborn dried blood spots on Guthrie cards. A promissory technique].

    PubMed

    Distéfano, Angélica L; González, Cecilia A; Pardón, Fabián; Sarubi, María A; Canero Velazco, Cristina

    2008-04-01

    Laboratories play a crucial role in the diagnosis of congenital and perinatal cytomegalovirus infection, considering that other viral infections in newborn infants have similar clinical characteristics. The objectives of this work are to compare the results of the polymerase reaction in blood spots and urine as well as point out the relevance of the result in the Guthrie cards to differentiate congenital from perinatal infection. A total of 148 patients suspicious of CMVH infections were studied in the Congenital Perinatal Infections and Sexual Transmission Laboratory, at the National Institute "Carlos G. Malbrán". The dry blood samples (Guthrie cards) and urine of all patients were studied through the polymerase chain reaction. From the 148 patients, 3 presented other infections, 95 tested negative and 50 positive for cytomegalovirus: 35 had congenital infection and 15 perinatal. In the congenital cases, the polymerase reaction in dry blood was positive (sensitivity 100%, specificity 98.9%, VPP 98% and VPN 100%). Four of them with tardive symptoms were studied retrospectively. The urine specimens from the remaining 15 patients that were taken 15 days after birth were analyzed through the same methods, showing a sensitivity of 100%, the retrospective analysis of this dry blood group yielded negative results, so the infection was considered perinatal. Thus, the dry blood polymerase reaction of the newborn infants makes it a reliable assay for diagnosing congenital cytomegalovirus infection and could be used as an alternative method to urine polymerase reaction. In addition, this test is able to reveal whether the infection is congenital or perinatal in those cases of late symptom or other cases of controversial origin. PMID:18661038

  17. Acute Human Cytomegalovirus Infection with Bleeding in Iran

    PubMed Central

    Pourhossein, Behzad; Yaghmaei, Farhad; Esmaeili, Saber; Banafshi, Omid; Afrasiabian, Shahla; Shirzadi, Mohammad Reza; Schleiss, Mark; Mostafavi, Ehsan

    2014-01-01

    In December 2011, a 42-year-old male farmer was admitted to a hospital in Sanandaj (Western Iran) with fever and anemia in order to check whether he suffered from some infectious diseases. During the first 3 days after admission, the patient gradually developed progressive oliguria, fever, abdominal pain in the right upper quadrant, leukocytosis with toxic granulation, petechiae and ecchymosis, oral bleeding, and vomiting. The sonographic findings revealed splenomegaly and an increase in the thickness of the gall bladder wall. In order to manage the patient and taking into consideration the most probable differential diagnoses, diagnostic tests were performed on two blood samples collected from him, and real-time polymerase chain reaction for human cytomegalovirus was positive. PMID:25562049

  18. Evasion of CD8+ T cells is critical for super-infection by cytomegalovirus$

    PubMed Central

    Hansen, Scott G.; Powers, Colin J.; Richards, Rebecca; Ventura, Abigail B.; Ford, Julia C.; Siess, Don; Axthelm, Michael K.; Nelson, Jay A.; Jarvis, Michael A.; Picker, Louis J.; Früh, Klaus

    2010-01-01

    Cytomegalovirus (CMV) can super-infect persistently infected hosts despite CMV-specific humoral and cellular immunity; however, how it does so remains undefined. Here, we demonstrate that super-infection of rhesus CMV-infected rhesus macaques (RM) requires evasion of CD8+ T cell immunity by virally-encoded inhibitors of MHC-I antigen presentation, particularly the homologues of human CMV US2, 3, 6 and 11. In contrast, MHC-I interference was dispensable for primary infection of RM, or for the establishment of a persistent secondary infection in CMV-infected RM transiently depleted of CD8+ lymphocytes. These findings demonstrate that US2-11 glycoproteins promote evasion of CD8+ T cells in vivo thus supporting viral replication and dissemination during super-infection, a process that complicates the development of preventative CMV vaccines, but that can be exploited for CMV-based vector development. PMID:20360110

  19. Management of cytomegalovirus infection in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

    PubMed

    Torre-Cisneros, J; Aguado, J M; Caston, J J; Almenar, L; Alonso, A; Cantisán, S; Carratalá, J; Cervera, C; Cordero, E; Fariñas, M C; Fernández-Ruiz, M; Fortún, J; Frauca, E; Gavaldá, J; Hernández, D; Herrero, I; Len, O; Lopez-Medrano, F; Manito, N; Marcos, M A; Martín-Dávila, P; Monforte, V; Montejo, M; Moreno, A; Muñoz, P; Navarro, D; Pérez-Romero, P; Rodriguez-Bernot, A; Rumbao, J; San Juan, R; Vaquero, J M; Vidal, E

    2016-07-01

    Cytomegalovirus (CMV) infection remains a major complication of solid organ transplantation. Because of management of CMV is variable among transplant centers, in 2011 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, new publications have clarified or questioned the aspects covered in the previous document. For that reason, a panel of experts revised the evidence on CMV management, including immunological monitoring, diagnostics, prevention, vaccines, indirect effects, treatment, drug resistance, immunotherapy, investigational drugs, and pediatric issues. This document summarizes the recommendations. PMID:27132815

  20. Human cytomegalovirus (HCMV) immediate-early enhancer/promoter specificity during embryogenesis defines target tissues of congenital HCMV infection.

    PubMed Central

    Koedood, M; Fichtel, A; Meier, P; Mitchell, P J

    1995-01-01

    Congenital human cytomegalovirus (HCMV) infection is a common cause of deafness and neurological disabilities. Many aspects of this prenatal infection, including which cell types are infected and how infection proceeds, are poorly understood. Transcription of HCMV immediate-early (IE) genes is required for expression of all other HCMV genes and is dependent on host cell transcription factors. Cell type-specific differences in levels of IE transcription are believed to underlie differences in infection permissivity. However, DNA transfection experiments have paradoxically suggested that the HCMV major IE enhancer/promoter is a broadly active transcriptional element with little cell type specificity. In contrast, we show here that expression of a lacZ gene driven by the HCMV major IE enhancer/promoter -524 to +13 segment is restricted in transgenic mouse embryos to sites that correlate with known sites of congenital HCMV infection in human fetuses. This finding suggests that the IE enhancer/promoter is a major determinant of HCMV infection sites in humans and that transcription factors responsible for its regulation are cell type-specifically conserved between humans and mice. The lacZ expression patterns of these transgenic embryos yield insight into congenital HCMV pathogenesis by providing a spatiotemporal map of the sets of vascular, neural, and epithelial cells that are likely targets of infection. These transgenic mice may constitute a useful model system for investigating IE enhancer/promoter regulation in vivo and for identifying factors that modulate active and latent HCMV infections in humans. PMID:7884867

  1. Predictors of severity for postnatal cytomegalovirus infection in preterm infants and implications for treatment.

    PubMed

    Gunkel, Julia; Wolfs, Tom F W; de Vries, Linda S; Nijman, Joppe

    2014-11-01

    Postnatal cytomegalovirus (CMV) infection is common in neonates and is mostly acquired through infected breast milk from seropositive mothers. In this review, risk factors of postnatal CMV transmission and predictors of severity, preventive measures and treatment of symptomatic postnatal CMV infection in preterm infants are discussed. Several viral, transmission route and host factors have been associated with a higher risk of postnatal CMV transmission from mother to child. Severity predictors of symptomatic postnatal CMV infection may include extreme prematurity (gestational age <26 weeks), timing of postnatal infection as well as comorbidities. Further research in postnatally infected preterm infants at risk for severe symptoms is essential with respect to preventive measures involving the infected breast milk and antiviral treatment. PMID:25277116

  2. Design of cocktail peptide vaccine against Cytomegalovirus infection

    PubMed Central

    Tabaei, Samira; Mashkani, Baratali; Esmaili, Arezoo; Karimi, Reza; Jamehdar, Saeid Amel

    2016-01-01

    Objective(s): Human Cytomegalovirus (HCMV) remains a major morbidity and mortality cause in immuno suppressed patients. Therefore, significant effort has been made towards the development of a vaccine. In this study, the expression of the pp65 and gB fusion peptides and Fc domain of mouse IgG2a as a novel delivery system for selective uptake of antigens by antigen-presenting cells (APCs) in Pichia pastoris yeast system were studied. Materials and Method: In this study, four immune dominant sequences in pp65 protein and 3 immuno dominant sequences in gB protein were selected according to literature review. Peptide linker -GGGGS- was used for construction of fusion peptide. This fusion peptide was cloned in the pPICZαA expression vector and transfected into P. pastoris host cells. Results: Dot blot and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) techniques showed that a high level of pp65-gB-Fc fusion peptide was expressed. Conclusion: This CMV pp65-gB-Fc fusion peptide could be a promising candidate for the development of a novel peptide vaccine. PMID:27279990

  3. A young patient with multisystem complications after cytomegalovirus infection.

    PubMed

    Pulivarthi, Swaroopa; Gurram, Murali Krishna

    2014-01-01

    We are describing a case of an 18-year-old male patient with cytomegalovirus (CMV) associated guillain-barre syndrome (GBS) who presented with an acute onset of generalized weakness and numbness in the extremities, dysphagia, and facial diplegia, followed by respiratory failure, which led to mechanical ventilation. He had positive immunoglobulin G and immunoglobulin M antibodies against CMV, and CMV polymerase chain reaction was positive with <2000 copies of deoxyribonucleic acid. Human immunodeficiency virus test was negative. He received a course of ganciclovir, intravenous immunoglobulin, and plasmapheresis. After improving from acute episode, patient was transferred to a rehabilitation facility for physical and occupational therapy. At the rehabilitation facility, he exhibited signs of acute abdomen with pain in the left upper quadrant secondary to peritonitis from dislodged gastrostomy tube and underwent exploratory laparotomy. During the hospital course he was found to have splenic infarct and colitis on the computed tomography of abdomen. This case showed an immunocompetent young patient with multisystem complications including guillain-barre syndrome (GBS), splenic infarct, hepatitis, and colitis due to CMV. PMID:24741254

  4. [Ménétrieŕs disease associated with cytomegalovirus infection].

    PubMed

    Fernández Caamaño, B; Ramos Boluda, E; Martínez-Ojinaga Nodal, E; Molina Arias, M; Sarría Osés, J; Prieto Bozano, G

    2015-01-01

    Menetrier's disease is a rare entity in children, characterized by a protein-losing gastroenteropathy with thickening of the gastric mucosa and generalized edema. The most common etiology is viral, and cytomegalovirus is the agent most frequently implicated. Unlike in the adult, it is a self-limited disorder with a good prognosis in children. Four patients (three boys and one girl) diagnosed with Ménétrier disease in the past five years were reviewed. The mean age at presentation was 28.7 months (range: 10-48 months). The most common clinical symptoms were fever, vomiting, and edema. Endoscopy showed thickened gastric folds and erosions in several stages. All patients had an associated gastric cytomegalovirus infection, and a favorable outcome, with resolution of the disorder,was observed within a few weeks. PMID:24666786

  5. Pulmonary embolism and acute cytomegalovirus infection in an immunocompetent patient.

    PubMed

    Del Borgo, Cosmo; Gianfreda, Romina; Belvisi, Valeria; Citton, Rita; Soscia, Fabrizio; Notarianni, Ermanno; Tieghi, Tiziana; Mastroianni, Claudio Maria

    2010-12-01

    A case of an immunocompetent man with acute CMV infection associated with a pulmonary embolism is described. Acute CMV infection could be a risk factor for developing thromboembolism. Pulmonary embolism should be included in differential diagnosis in patients with acute CMV infections and pulmonary opacities. PMID:21196823

  6. Impact of persistent cytomegalovirus infection on human neuroblastoma cell gene expression.

    PubMed

    Hoever, Gerold; Vogel, Jens-Uwe; Lukashenko, Polina; Hofmann, Wolf-Karsten; Komor, Martina; Doerr, Hans Wilhelm; Cinatl, Jindrich

    2005-01-14

    In a model of human neuroblastoma (NB) cell lines persistently infected with human cytomegalovirus (HCMV) we previously showed that persistent HCMV infection is associated with an increased malignant phenotype, enhanced drug resistance, and invasive properties. To gain insights into the mechanisms of increased malignancy we analyzed the global changes in cellular gene expression induced by persistent HCMV infection of human neuroblastoma cells by use of high-density oligonucleotide microarrays (HG-U133A, Affymetrix) and RT-PCR. Comparing the gene expression of different NB cell lines with persistently infected cell sub-lines revealed 11 host cell genes regulated in a similar manner throughout all infected samples. Nine of these 11 genes may contribute to the previously observed changes in malignant phenotype of persistently HCMV infected NB cells by influencing invasive growth, apoptosis, angiogenesis, and proliferation. Thus, this work provides the basis for further functional studies. PMID:15582591

  7. An atypical case of acute disseminated encephalomyelitis associated with cytomegalovirus infection.

    PubMed

    De Fino, Chiara; Nociti, Viviana; Modoni, Anna; Bizzarro, Alessandra; Mirabella, Massimiliano

    2016-01-01

    We present the case of a young man admitted to our hospital for persistent headache associated with fever, retrorbitary pain and vomiting, who rapidly developed encephalopathy with drowsiness, paraplegia, hypoesthesia with a D6 sensory level and urinary retention. Brain and spinal cord MRI revealed findings compatible with acute disseminated encephalomyelitis (ADEM) and microbiological tests documented a cytomegalovirus (CMV) infection. CMV infection is extraordinarily associated with ADEM, but must be included in microbiological tests, because early diagnosis and treatment ameliorate the neurological outcome. PMID:26856946

  8. Cutaneous cytomegalovirus infection on multi dermatomal herpes zoster scars: an isotopic immune response.

    PubMed

    Katibi, O S; Dlova, N C; Mosam, A

    2015-01-01

    As more patients with human immunodeficiency virus (HIV) are surviving, despite severe immune suppression, clinicians are faced with atypical manifestations of both common and uncommon dermatoses. A 30-year-old black South African woman presented with a 10-month history of multiple chronic ulcers appearing on a multidermatomal herpes zoster (HZ) scar. The woman was infected with HIV, and her CD4 count was 45 cells/μL. Histology and PCR revealed cytomegalovirus (CMV) infection. This case highlights an unusual presentation of cutaneous CMV occurring as an isotopic immune response on a pre-existing multidermatomal HZ scar. PMID:25266481

  9. Cytomegalovirus Infection after CD34(+)-Selected Hematopoietic Cell Transplantation.

    PubMed

    Huang, Yao-Ting; Neofytos, Dionysios; Foldi, Julia; Kim, Seong Jin; Maloy, Molly; Chung, Dick; Castro-Malaspina, Hugo; Giralt, Sergio A; Papadopoulos, Esperanza; Perales, Miguel-Angel; Jakubowski, Ann A; Papanicolaou, Genovefa A

    2016-08-01

    The effectiveness of preemptive treatment (PET) for cytomegalovirus (CMV) in recipients of ex vivo T cell-depleted (TCD) hematopoietic cell transplantation (HCT) by CD34(+) selection is not well defined. We analyzed 213 adults who received TCD-HCT at our institution from June 2010 through May 2014. Patients were monitored by a CMV quantitative PCR assay if recipient (R) or donor (D) were CMV seropositive. CMV viremia occurred early (median, 27 days after HCT) in 91 of 213 (42.7%) patients for a 180-day cumulative incidence of 84.5%, 61.8%, and 0 for R+/D+, R+/D-, and R-/D+ patients, respectively. CMV disease occurred in 5% of patients. In Cox regression analysis, R+/D+ status was associated with increased risk for CMV viremia compared with R+/D- (hazard ratio [HR], 1.79, 95% confidence interval [CI], 1.16 to 2.76, P = .01), whereas matched unrelated donor allograft was associated with decreased risk (HR, .62; 95% CI, .39 to .97, P = .04). Of 91 patients with CMV viremia, 52 (57%) had persistent viremia (>28 days duration). Time lag from detection of CMV viremia to PET was associated with incremental risk for persistent viremia (HR, 1.09; 95% CI, 1.01 to 1.18; P = .03). Overall, 166 of 213 (77.9%) patients were alive 1 year after HCT, with no difference between patients with and without CMV viremia or among the different CMV serostatus pairs (P = not significant). CMV viremia occurred in 70% of R + TCD-HCT. Delay in PET initiation was associated with persistent viremia. With PET, CMV R/D serostatus did not adversely impact survival in TCD-HCT on 1-year survival in the present cohort. PMID:27178374

  10. The presence of precursors of benign pre-B lymphoblasts (hematogones) in the bone marrow of a paediatric patient with cytomegalovirus infection.

    PubMed

    Moreno-Madrid, F; Uberos, J; Díaz-Molina, M; Ramírez-Arredondo, A; Jiménez-Gámiz, P; Molina-Carballo, A

    2008-01-01

    Hematogones are normal B-lymphoid precursors that multiply in the bone marrow of small children and of adults with ferropenic anaemia, neuroblastoma or idiopathic thrombocytopenic purpura. They are not normally found in peripheral blood, and the immunophenotype is virtually indistinguishable from that of B lymphoblasts. We discuss the case of a 3-month infant with an active cytomegalovirus infection, with hepatitis and pancytopenia associated with 13% hematogones in the bone marrow. PMID:21892313

  11. Invasive gastric mucormycosis and cytomegalovirus infection in an ABO incompatible renal transplant recipient.

    PubMed

    Nandwani, A; Jha, P K; Duggal, R; Kher, V

    2015-01-01

    Opportunistic infections are common in immunocompromised patients, such as solid organ transplant recipients. Both fungal and viral infections in posttransplant period increase morbidity and mortality. Cytomegalovirus (CMV) remains one of the most important pathogens. CMV disease may manifest as a nonspecific febrile syndrome or tissue-invasive infections. Zygomycosis is a rare infection, usually presents in rhino-cerebral, pulmonary and disseminated forms; gastrointestinal (GI) tract being a rare site of involvement. Newer techniques for early diagnosis and efficient therapies are essential for a better outcome of the disease; however, mortality rate remains high despite aggressive therapy. We report a renal transplant recipient, who developed gastric mucormycosis along with tissue invasive CMV disease, within 4 weeks of renal transplant and was diagnosed on the basis of upper GI endoscopy and gastric biopsy. The patient succumbed to the infection in spite of gastrectomy, antifungal and antiviral therapy. PMID:26664215

  12. Perforation of the bowel due to cytomegalovirus infection in a man with AIDS: surgery is not always necessary!

    PubMed

    Yoganathan, Katie Tharshana; Morgan, Andrew Roger; Yoganathan, Kathir G

    2016-01-01

    Cytomegalovirus (CMV) infection is the most common viral opportunistic infection in immunocompromised patients and is a rare cause of bowel perforation. It invariably requires surgical intervention and is often fatal. We report a 50-year-old Caucasian man with AIDS, presented 3 weeks after developing abdominal pain and distension. He was treated for CMV retinitis in the past. His adherence to antiretroviral therapy was poor. Examination revealed a recurrence of active CMV retinitis. His abdomen was tender and distended. The plain X-ray of the abdomen revealed a double wall sign (Rigler's sign), indicating pneumoperitoneum due to the bowel perforation. The upper endoscopy was normal. His CD4 count was 30 cells/mm(3) He was treated with cidofovir infusion. He made a full recovery, without requiring any form of surgery. However, he died of adult respiratory distress syndrome 14 months later, due to iatrogenic acute pancreatitis. PMID:27440845

  13. Regulation of CCAAT/enhancer-binding protein (C/EBP) α in human-cytomegalovirus-infected fibroblasts.

    PubMed

    Lee, Junsub; Kim, Sunyoung

    2016-05-01

    CCAAT/enhancer-binding protein (C/EBP) α, a member of the C/EBP family of transcription factors, is known to be involved in gene expression and DNA replication of human cytomegalovirus (HCMV). This study aimed to understand the regulation of endogenous C/EBPα during HCMV infection using an in vitro infection model. The expression and localization of C/EBPα were investigated in fibroblasts infected with HCMV. The overexpression of C/EBP homologous protein (CHOP), the endogenous inhibitor of C/EBP, was also employed to test the involvement of C/EBPα during HCMV infection. Our data showed that HCMV infection increases the expression of the full-length C/EBPα isoform (p42) especially during the late stage of infection at the transcriptional and post-translational levels. The increased p42 accumulated in the viral DNA replication compartment. p42 expression was not induced in cells treated with UV-irradiated virus or in cells infected with normal virus in the presence of ganciclovir. CHOP-mediated inhibition of C/EBP activity suppressed viral gene expression and DNA replication, which lowered the level of viral production. Together, our data suggest that HCMV-mediated C/EBPα regulation might play a beneficial role in the lytic cycle of HCMV. PMID:26831934

  14. The Influence of Primary Cytomegalovirus or Epstein-Barr Virus Infection on the Course of Idiopathic Thrombocytopenic Purpura.

    PubMed

    Smalisz-Skrzypczyk, Katarzyna; Romiszewski, Michał; Matysiak, Michał; Demkow, Urszula; Pawelec, Katarzyna

    2016-01-01

    Idiopathic thrombocytopenic purpura (ITP) in children is usually triggered by a viral infections such as cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection. The aim of this study was to assess the frequency of CMV and EBV infections in children with first relapse of ITP, and the influence of these infections on the course and response to treatment of ITP. Sixty patients (30 boys and 30 girls) with ITP were enrolled into the study. We found that the age at the onset of ITP was from 1 month to 17 years (mean 7.0 ± 5.7 years), the platelet number was from 1 to 79 x 10(9)/L (mean 18.1 ± 19.0 x 10(9)/L) at the time of diagnosis and it increased from 17 to 395 x 10(9)/L (mean 134.4 ± 81.2 x 10(9)/L)(p < 0.05) after the first course of therapy. Forty seven patients required pharmacological treatment, the duration of the treatment was from 2 to 25 days (mean 6.1 ± 4.1 days). Relapses were observed in 27 (45%) of the patients. Active CMV infection was found in 19 patients (31.7%), EBV infection in 5 patients (8.3%), and both infections concomitantly in 1 patient (1.7%). The group of patients with CMV or EBV infection(n = 25) did not differ from the patients free of infection (n = 35) in regard to the age, number of platelets at onset, duration of treatment, number of platelets after treatment, number of relapses, and the interval between the onset and first relapse. In conclusion, active CMV or EBV infection is common in children with ITP. These infections do not seem to have an appreciable bearing on the clinical course and the response to treatment on children with ITP. PMID:26269027

  15. Hepatic decompensation in the absence of obvious precipitants: the potential role of cytomegalovirus infection/reactivation

    PubMed Central

    Rosi, Silvia; Poretto, Valentina; Cavallin, Marta; Angeli, Paolo; Amodio, Piero; Sattin, Andrea; Montagnese, Sara

    2015-01-01

    Details of two patients with alcohol-related and mixed aetiology cirrhosis who developed acute-on-chronic liver failure/hepatic decompensation with no obvious precipitants are reported. Cytomegalovirus (CMV) infection or reactivation was diagnosed in both, and required treatment with ganciclovir in one. Both returned to baseline hepatic function and remain well. Physicians should be alert to the possibility that CMV might cause or contribute to hepatic decompensation in patients with cirrhosis, even if they are not severely immunocompromised, and especially if they are alcohol misusers. PMID:26629358

  16. Metabolism of Cyclopropavir and Ganciclovir in Human Cytomegalovirus-Infected Cells

    PubMed Central

    Drach, John C.

    2014-01-01

    Human cytomegalovirus (HCMV) is a widespread pathogen that can cause severe disease in immunologically immature and immunocompromised patients. The current standard of therapy for the treatment of HCMV infections is ganciclovir (GCV). However, high incidence rates of adverse effects are prevalent and limit the use of this drug. Cyclopropavir (CPV) is 10-fold more effective against HCMV in vitro than GCV (50% effective concentrations [EC50s] = 0.46 and 4.1 μM, respectively) without any observed increase in cytotoxicity (S. Zhou, J. M. Breitenbach, K. Z. Borysko, J. C. Drach, E. R. Kern, E. Gullen, Y. C. Cheng, and J. Zemlicka, J. Med. Chem. 47:566–575, 2004, doi:10.1021/jm030316s). We have previously determined that the viral protein kinase pUL97 and endogenous cellular kinases are responsible for the conversion of CPV to a triphosphate (TP), the active compound responsible for inhibiting viral DNA synthesis and viral replication. However, this conversion has not been observed in HCMV-infected cells. To that end, we subjected HCMV-infected cells to equivalently effective concentrations (∼5 times the EC50) of either CPV or GCV and observed a time-dependent increase in triphosphate levels for both compounds (CPV-TP = 121 ± 11 pmol/106 cells; GCV-TP = 43.7 ± 0.4 pmol/106 cells). A longer half-life was observed for GCV-TP (48.2 ± 5.7 h) than for CPV-TP (23.8 ± 5.1 h). The area under the curve for CPV-TP produced from incubation with 2.5 μM CPV was 8,680 ± 930 pmol · h/106 cells, approximately 2-fold greater than the area under the curve for GCV-TP of 4,520 ± 420 pmol · h/106 cells produced from incubation with 25 μM GCV. We therefore conclude that the exposure of HCMV-infected cells to CPV-TP is greater than that of GCV-TP under these experimental conditions. PMID:24514084

  17. Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults.

    PubMed

    de Pablo-Bernal, Rebeca Sara; Cañizares, Julio; Rosado, Isaac; Galvá, María Isabel; Alvarez-Ríos, Ana Isabel; Carrillo-Vico, Antonio; Ferrando-Martínez, Sara; Muñoz-Fernández, María Ángeles; Rafii-El-Idrissi Benhnia, Mohammed; Pacheco, Yolanda María; Ramos, Raquel; Leal, Manuel; Ruiz-Mateos, Ezequiel

    2016-05-01

    Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67-90] years old;n= 20) compared with young controls (median 35 [27-40] years old;n= 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p= .001), IL1-β (p= .001), IL-6 (p= .002), and IL-8 (p= .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline. PMID:26286603

  18. [Cytomegalovirus and other herpes virus infections in systemic diseases].

    PubMed

    Michaux, Christian; Morlat, Philippe; Bonnet, Fabrice

    2010-01-01

    Reactivation of Herpesviridae is well known among transplant patients, but has not been sufficiently studied in patients who receive immunosuppressive treatment for systemic inflammatory diseases. CMV infection seems relatively rare; it is easily diagnosed by real-time PCR, a fast and reliable diagnostic tool. CMV disease is most often manifested in the form of lung disease, hepatitis, or colitis. The highest risks are associated with steroid or cyclophosphamide boluses and methotrexate. Prophylactic treatment cannot be recommended in clinical practice. The utility of monitoring viremia and of preemptive therapy must be evaluated. Herpes zoster is the most frequent viral infection in systemic diseases. Most immunosuppressive treatments, except methotrexate, promote its occurrence. Visceral involvement is quite rare, and outcome almost always favorable. Prophylactic treatment cannot be recommended. PMID:19446998

  19. Strategies to control human cytomegalovirus infection in adult hematopoietic stem cell transplant recipients.

    PubMed

    Lilleri, Daniele; Gerna, Giuseppe

    2016-09-01

    Human cytomegalovirus (HCMV) represents the major viral complication after hematopoietic stem cell transplantation. HCMV infection may be controlled by the reconstituting immune system and remain subclinical or can lead to severe systemic and/or organ disease (mainly pneumonia and gastroenteritis) when immune reconstitution is delayed or impaired. In order to prevent the occurrence of HCMV disease, a prompt diagnosis of HCMV infection is mandatory. The adoption of pre-emptive therapy strategies guided by virological monitoring dramatically reduced the occurrence of HCMV disease. However, late-onset end-organ disease may occur in some patients with apparent immune reconstitution. In the near future, introduction of immunological monitoring and immunotherapies could markedly improve management of HCMV infection. PMID:27485084

  20. Cytomegalovirus infection: its incidence and management in cytomegalovirus-seropositive living related liver transplant recipients: a single-center experience.

    PubMed

    Wadhawan, Manav; Gupta, Subash; Goyal, Neerav; Vasudevan, Karisangal R; Makki, Kausar; Dawar, Reetika; Sardana, Raman; Lal, Nand; Kumar, Ajay

    2012-12-01

    It is believed that antiviral prophylaxis decreases the incidence of cytomegalovirus (CMV) reactivation and disease. There are few data regarding weekly assays for CMV DNA after transplantation and the subsequent management of CMV. Here we report a cohort of living related liver transplantation (LRLT) patients who were treated for invasive CMV disease or for CMV infections if they were receiving steroids for rejection. Patients who underwent liver transplantation at our center between September 2006 and August 2010 and were recipient-positive/donor-positive (R(+) /D(+) ) were prospectively included. Patients were tested for CMV DNA 3 weeks after transplantation. CMV DNA-positive patients underwent weekly DNA monitoring until there were 2 consecutive negative reports. Those who developed CMV disease or had rising DNA titers while they were on treatment for rejection were treated. A Cox regression analysis was performed for factors predicting survival. Two hundred sixty-six of the 306 R(+) /D(+) patients were CMV DNA-negative 3 weeks after transplantation, and 40 had detectable DNA. One of the DNA-negative patients developed CMV disease after treatment for rejection with methylprednisolone. Thirty patients had <500 copies/mL, and 10 had ≥500 copies/mL. Two of the 30 patients with DNA levels < 500 copies/mL developed CMV disease. Six of the 10 patients with DNA levels ≥500 copies/mL developed disease. CMV disease occurred in 9 of the 306 patients (2.9%). One patient received treatment for a rise in DNA titers while he was receiving steroids. There was a significant correlation between steroid administration for acute cellular rejection (ACR) and CMV reactivation (P = 0.003) and disease (P = 0.002). A multivariate analysis showed that CMV reactivation/disease did not predict survival. There was no difference in survival between CMV DNA-positive patients and CMV DNA-negative patients (P = 0.68). In conclusion, CMV reactivation is common after LRLT (13%), but the

  1. The effect of cytomegalovirus infection on acute rejection in kidney transplanted patients

    PubMed Central

    Hasanzamani, Boshra; Hami, Maryam; Zolfaghari, Vajihe; Torkamani, Mahtab; Ghorban Sabagh, Mahin; Ahmadi Simab, Saiideh

    2016-01-01

    Introduction: It is known that cytomegalovirus (CMV) infection is a common problem among kidney transplant patients. This infection can be increased morbidity and decreased graft survival. This problem has been associated with acute rejection too. Patients and Methods: One hundred and thirty renal transplant patients were included in a prospective, case-control study. The renal transplant patients were divided into two groups; patients group with CMV infection and control group without CMV infection. Serum CMV-IgG in all patients was positive (donor and recipients). None of patients had received anti-thymocyte-globulin and thymoglobulin. CMV infection was diagnosed by quantitative CMV-PCR (polymerase chain reaction) test (more than 500 copies/μg). Rejection episode was defined by kidney isotope scan or biopsy. Results: In the group of 66 CMV infection patients (41 male [62.1%] and 25 female [37.9%]) the incidence of graft rejection was 36%, however in the group of 64 control patients the incidence of graft rejection was 9.4 % (P < 0.005). Conclusion: CMV infection is important predisposing factor for acute allograft rejection after kidney transplantation. The results of this study suggests that the control of CMV infection could decrease episodes of acute kidney rejection. PMID:27471740

  2. [Review and guidelines on the prevention, diagnosis and treatment of post-natal cytomegalovirus infection].

    PubMed

    Alarcón Allen, A; Baquero-Artigao, F

    2011-01-01

    Postnatal cytomegalovirus (CMV) infection in the newborn can occur from exposure to maternal cervical secretions during birth, ingestion of breast milk, transfusion of blood products or transmission by body fluids of infected people. Breast milk is the main source of infection, given the high rate of CMV-positive mothers excreting CMV in milk. Freezing reduces the risk of CMV transmission by breastfeeding, although it does not eliminate it completely. Pasteurisation prevents such transmission, but it can alter the immunological properties of breast milk. Postnatal CMV infection is usually asymptomatic, as it normally results from viral reactivation in the mother, and the neonate is born with protective antibodies. However, in the very low birth weight premature infant the amount of transferred antibodies is smaller and a symptomatic infection can occur. Symptomatic post-natal CMV infection in the newborn typically causes hepatitis, neutropenia, thrombocytopenia or sepsis-like syndrome. Pneumonitis and enteritis are less common, but very characteristic. Diagnosis is based on urine virus detection at the time of onset of symptoms. Postnatal CMV infection in the newborn generally resolves spontaneously without antiviral treatment. Ganciclovir should be reserved for severe cases. Unlike congenital CMV disease, post-natal CMV infection in the preterm infant does not seem to be associated with hearing loss or abnormal neuro-development in long term follow-up. PMID:20630814

  3. Cytomegalovirus infection enhances smooth muscle cell proliferation and intimal thickening of rat aortic allografts.

    PubMed Central

    Lemström, K B; Bruning, J H; Bruggeman, C A; Lautenschlager, I T; Häyry, P J

    1993-01-01

    Inbred DA (AG-B4, RT1a) and WF (AG-B2, RT1v) rats were used as donors and recipients of aortic allografts. The recipient rats were inoculated i.p. either on day 1 (early infection) or on day 60 (late infection) with 10(5) plaque-forming units of rat cytomegalovirus (RCMV). The control rats were left noninfected. The presence of viral infection was demonstrated by plaque assays from biopsies of the salivary glands, liver, and spleen at sacrifice. The rats received 300 microCi[3H]thymidine by i.v. injection 3 h before sacrifice, and the grafts were removed at various time points for histology, immunohistochemistry, and autoradiography. RCMV infection significantly enhanced the generation of allograft arteriosclerosis. Infection at the time of transplantation had two important effects. First, the infection was associated with an early, prominent inflammatory episode and proliferation of inflammatory cells in the allograft adventitia. Second, the viral infection doubled the proliferation rate of smooth muscle cells and the arteriosclerotic alterations in the intima. In late infection the impact of RCMV infection on the allograft histology was nearly nonexistent. RCMV infection showed no effect in syngeneic grafts. These results suggest that early infection is more important to the generation of accelerated allograft arteriosclerosis than late infection, and that an acute alloimmune response must be associated with virus infection, to induce accelerated allograft arteriosclerosis. RCMV-infected aortic allografts, as described here, provide the first experimental model to investigate the interaction between the virus and the vascular wall of the transplant. Images PMID:8394384

  4. Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant.

    PubMed

    Revello, Maria Grazia; Gerna, Giuseppe

    2002-10-01

    Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and mental retardation. HCMV infection, while causing asymptomatic infections in most immunocompetent subjects, can be transmitted during pregnancy from the mother with primary (and also recurrent) infection to the fetus. Hence, careful diagnosis of primary infection is required in the pregnant woman based on the most sensitive serologic assays (immunoglobulin M [IgM] and IgG avidity assays) and conventional virologic and molecular procedures for virus detection in blood. Maternal prognostic markers of fetal infection are still under investigation. If primary infection is diagnosed in a timely manner, prenatal diagnosis can be offered, including the search for virus and virus components in fetal blood and amniotic fluid, with fetal prognostic markers of HCMV disease still to be defined. However, the final step for definite diagnosis of congenital HCMV infection is detection of virus in the blood or urine in the first 1 to 2 weeks of life. To date, treatment of congenital infection with antiviral drugs is only palliative both prior to and after birth, whereas the only efficacious preventive measure seems to be the development of a safe and immunogenic vaccine, including recombinant, subunit, DNA, and peptide-based vaccines now under investigation. The following controversial issues are discussed in the light of the most recent advances in the field: the actual perception of the problem; universal serologic screening before pregnancy; the impact of correct counseling on decision making by the couple involved; the role of prenatal diagnosis in ascertaining transmission of virus to the fetus; the impact of preconceptional and periconceptional infections on the prevalence of congenital infection; and the prevalence of congenitally infected babies born to mothers who were immune prior to pregnancy compared to the number born to mothers undergoing primary infection during pregnancy. PMID

  5. Immune-based guidance of foscarnet treatment duration in a transplant recipient with ganciclovir-resistant cytomegalovirus infection.

    PubMed

    Mihm, Janine; Leyking, Sarah; Dirks, Jan; Smola, Sigrun; Fliser, Danilo; Sester, Urban; Sester, Martina; Wilkens, Heinrike; Rissland, Jürgen

    2016-09-01

    A lung and kidney transplant recipient underwent cytomegalovirus (CMV) primary infection with a UL97 mutation. Combined monitoring of viral load and CMV-specific CD4 T-cells allowed reduction of treatment duration with foscarnet, and illustrates how knowledge on the individual immunocompetence towards CMV may be used to individualize duration of antiviral treatment. PMID:27389910

  6. The life cycle and pathogenesis of human cytomegalovirus infection: lessons from proteomics

    PubMed Central

    Beltran, Pierre M. Jean; Cristea, Ileana M.

    2015-01-01

    Viruses have co-evolved with their hosts, acquiring strategies to subvert host cellular pathways for effective viral replication and spread. Human cytomegalovirus (HCMV), a widely-spread β-herpesvirus, is a major cause of birth defects and opportunistic infections in HIV-1/AIDS patients. HCMV displays an intricate system-wide modulation of the human cell proteome. An impressive array of virus–host protein interactions occurs throughout the infection. To investigate the virus life cycle, proteomics has recently become a significant component of virology studies. Here, we review the mass spectrometry-based proteomics approaches used in HCMV studies, as well as their contribution to understanding the HCMV life cycle and the virus-induced changes to host cells. The importance of the biological insights gained from these studies clearly demonstrate the impact that proteomics has had and can continue to have on understanding HCMV biology and identifying new therapeutic targets. PMID:25327590

  7. Clinical Findings and Autopsy of a Preterm Infant with Breast Milk-Acquired Cytomegalovirus Infection

    PubMed Central

    Anne-Aurélie, Lopes; Souad, Belhabri; Leila, Karaoui

    2016-01-01

    Background Nonpasteurized, nonfrozen, fresh breast milk from mothers with positive cytomegalovirus (CMV) serology was initially contraindicated to very low-birth-weight infants because of the risk of milk-acquired CMV infection. Recently, the severity of this infection was increasingly discussed and the international guidelines now differ. Since 2012, the American Academy of Pediatrics has recommended nutrition through raw breast milk for all preterm infants. Case We report the case of an infant born prematurely at 27 weeks and 4 days and fed with raw breastmilk from day 12 of life (D12). He presented with a late-onset of CMV infection from D39. The CMV polymerase chain reaction (PCR), negative on D3, was strongly positive on D49, as well as the PCR on breast milk. He had CMV-specific immunoglobulin (Ig) M while his mother had only CMV-specific IgG. On D52, he deteriorated further with septic shock, and a fatal cardiac arrest on D54. His twin presented an asymptomatic CMV infection. The autopsy and histological examination showed evidence of numerous organ damage caused by CMV (with differences compared with congenital infection) but no evidence of bacterial infection. Conclusion Although rare, postnatal CMV infections transmitted by raw breast milk given to very low-birthweight infants can have dramatic consequences. PMID:27257513

  8. Cytomegalovirus-Infected Cells Resist T Cell Mediated Killing in an HLA-Recognition Independent Manner.

    PubMed

    Proff, Julia; Walterskirchen, Christian; Brey, Charlotte; Geyeregger, Rene; Full, Florian; Ensser, Armin; Lehner, Manfred; Holter, Wolfgang

    2016-01-01

    In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. T cells engineered with this anti-gB CAR recognized HCMV-infected cells and released cytokines and cytotoxic granules. Unexpectedly, and in contrast to analogous approaches for HIV, Hepatitis B or Hepatitis C virus, we found that HCMV-infected cells were resistant to killing by the CAR-modified T cells. In order to elucidate whether this phenomenon was restricted to the use of CARs, we extended our experiments to T cell receptor (TCR)-mediated recognition of infected cells. To this end we infected fibroblasts with HCMV-strains deficient in viral inhibitors of antigenic peptide presentation and targeted these HLA-class I expressing peptide-loaded infected cells with peptide-specific cytotoxic T cells (CTLs). Despite strong degranulation and cytokine production by the T cells, we again found significant inhibition of lysis of HCMV-infected cells. Impairment of cell lysis became detectable 1 day after HCMV infection and gradually increased during the following 3 days. We thus postulate that viral anti-apoptotic factors, known to inhibit suicide of infected host cells, have evolved additional functions to directly abrogate T cell cytotoxicity. In line with this hypothesis, CAR-T cell cytotoxicity was strongly inhibited in non-infected fibroblasts by expression of the HCMV-protein UL37x1, and even more so by additional expression of UL36. Our data extend the current knowledge on Betaherpesviral evasion from T cell immunity and show for the first time that, beyond impaired antigen presentation, infected cells are efficiently protected by direct blockade of cytotoxic effector functions through viral proteins. PMID:27375569

  9. Cytomegalovirus-Infected Cells Resist T Cell Mediated Killing in an HLA-Recognition Independent Manner

    PubMed Central

    Proff, Julia; Walterskirchen, Christian; Brey, Charlotte; Geyeregger, Rene; Full, Florian; Ensser, Armin; Lehner, Manfred; Holter, Wolfgang

    2016-01-01

    In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. T cells engineered with this anti-gB CAR recognized HCMV-infected cells and released cytokines and cytotoxic granules. Unexpectedly, and in contrast to analogous approaches for HIV, Hepatitis B or Hepatitis C virus, we found that HCMV-infected cells were resistant to killing by the CAR-modified T cells. In order to elucidate whether this phenomenon was restricted to the use of CARs, we extended our experiments to T cell receptor (TCR)-mediated recognition of infected cells. To this end we infected fibroblasts with HCMV-strains deficient in viral inhibitors of antigenic peptide presentation and targeted these HLA-class I expressing peptide-loaded infected cells with peptide-specific cytotoxic T cells (CTLs). Despite strong degranulation and cytokine production by the T cells, we again found significant inhibition of lysis of HCMV-infected cells. Impairment of cell lysis became detectable 1 day after HCMV infection and gradually increased during the following 3 days. We thus postulate that viral anti-apoptotic factors, known to inhibit suicide of infected host cells, have evolved additional functions to directly abrogate T cell cytotoxicity. In line with this hypothesis, CAR-T cell cytotoxicity was strongly inhibited in non-infected fibroblasts by expression of the HCMV-protein UL37x1, and even more so by additional expression of UL36. Our data extend the current knowledge on Betaherpesviral evasion from T cell immunity and show for the first time that, beyond impaired antigen presentation, infected cells are efficiently protected by direct blockade of cytotoxic effector functions through viral proteins. PMID:27375569

  10. Human cytomegalovirus pUL97 kinase induces global changes in the infected cell phosphoproteome

    PubMed Central

    Oberstein, Adam; Perlman, David H.; Shenk, Thomas; Terry, Laura J.

    2015-01-01

    Replication of human cytomegalovirus is regulated in part by cellular kinases and the single viral Ser/Thr kinase, pUL97. The virus-coded kinase augments the replication of human cytomegalovirus (HCMV) by enabling nuclear egress and altering cell cycle progression. These roles are accomplished through direct phosphorylation of nuclear lamins and the retinoblastoma protein, respectively. In an effort to identify additional pUL97 substrates, we analyzed the phosphoproteome of SILAC-labeled human fibroblasts during infection with either wild-type HCMV or a pUL97 kinase-dead mutant virus. Phosphopeptides were enriched over a titanium dioxide matrix and analyzed by high resolution mass spectrometry. We identified 157 unambiguous phosphosites from 106 cellular and 17 viral proteins whose phosphorylation required UL97. Analysis of peptides containing these sites allowed the identification of several candidate pUL97 phosphorylation motifs, including a completely novel phosphorylation motif, LxSP. Substrates harboring the LxSP motif were enriched in nucleocytoplasmic transport functions, including a number of components of the nuclear pore complex. These results extend the known functions of pUL97 and suggest that modulation of nuclear pore function may be important during HCMV replication. PMID:25867546

  11. The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions

    PubMed Central

    Shitrit, Alina; Shani, Odem; Le-Trilling, Vu Thuy Khanh; Trilling, Mirko; Friedlander, Gilgi; Tanenbaum, Marvin; Stern-Ginossar, Noam

    2015-01-01

    Viruses are by definition fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt this machinery for their own benefit. Unlike many viruses, human cytomegalovirus (HCMV) does suppress the host translation machinery, and the extent to which translation machinery contributes to the overall pattern of viral replication and pathogenesis remains elusive. Here, we combine RNA sequencing and ribosomal profiling analyses to systematically address this question. By simultaneously examining the changes in transcription and translation along HCMV infection, we uncover extensive transcriptional control that dominates the response to infection, but also diverse and dynamic translational regulation for subsets of host genes. We were also able to show that, at late time points in infection, translation of viral mRNAs is higher than that of cellular mRNAs. Lastly, integration of our translation measurements with recent measurements of protein abundance enabled comprehensive identification of dozens of host proteins that are targeted for degradation during HCMV infection. Since targeted degradation indicates a strong biological importance, this approach should be applicable for discovering central host functions during viral infection. Our work provides a framework for studying the contribution of transcription, translation and degradation during infection with any virus. PMID:26599541

  12. The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions.

    PubMed

    Tirosh, Osnat; Cohen, Yifat; Shitrit, Alina; Shani, Odem; Le-Trilling, Vu Thuy Khanh; Trilling, Mirko; Friedlander, Gilgi; Tanenbaum, Marvin; Stern-Ginossar, Noam

    2015-01-01

    Viruses are by definition fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt this machinery for their own benefit. Unlike many viruses, human cytomegalovirus (HCMV) does suppress the host translation machinery, and the extent to which translation machinery contributes to the overall pattern of viral replication and pathogenesis remains elusive. Here, we combine RNA sequencing and ribosomal profiling analyses to systematically address this question. By simultaneously examining the changes in transcription and translation along HCMV infection, we uncover extensive transcriptional control that dominates the response to infection, but also diverse and dynamic translational regulation for subsets of host genes. We were also able to show that, at late time points in infection, translation of viral mRNAs is higher than that of cellular mRNAs. Lastly, integration of our translation measurements with recent measurements of protein abundance enabled comprehensive identification of dozens of host proteins that are targeted for degradation during HCMV infection. Since targeted degradation indicates a strong biological importance, this approach should be applicable for discovering central host functions during viral infection. Our work provides a framework for studying the contribution of transcription, translation and degradation during infection with any virus. PMID:26599541

  13. Comparison of Presentation, Course, and Outcome of Congenital and Acquired Cytomegalovirus Infection in Twins

    PubMed Central

    Samedi, Veronica Mugarab; Skappak, Christopher; Jantzie, Lindsay; Trevenen, Cynthia; Kamaluddeen, Majeeda; Ekwalanga, Pauline; Al Awad, Essa Hamdan

    2015-01-01

    Background Cytomegalovirus (CMV) is one of the most common causes of serious viral intrauterine infections. It is universally distributed among the human population with an average incidence of 0.15 to 2%. Indeed, at least half of the women in the reproductive age have evidence of prior CMV infection. Epidemiology and Pathogenicity However, it is not a usual practice to screen asymptomatic pregnant woman or neonates for CMV. Even if a mother developed a primary CMV infection during pregnancy, up to 90% of the newborns with congenital CMV will be asymptomatic at the time of birth. Only 5 to 7% of the infected babies will be acutely symptomatic, and the typical clinical presentation includes intrauterine growth restriction, microcephaly, various cutaneous manifestations (including petechiae and purpura), hematological abnormalities (particularly resistant thrombocytopenia), hepatosplenomegaly, chorioretinitis, hepatitis, etc. In contrast, acquired CMV infection is extremely unlikely to cause any serious sequelae for the infant. Cases  We present a case of congenital and acquired CMV infection in twins with a focus of dissimilarity in presentation, clinical course, and outcome. PMID:26929859

  14. Mast cells: innate attractors recruiting protective CD8 T cells to sites of cytomegalovirus infection.

    PubMed

    Podlech, Jürgen; Ebert, Stefan; Becker, Marc; Reddehase, Matthias J; Stassen, Michael; Lemmermann, Niels A W

    2015-06-01

    Reactivation of latent cytomegalovirus (CMV) in the transient immunocompromised state after hematoablative treatment is a major concern in patients undergoing hematopoietic cell transplantation (HCT) as a therapy of hematopoietic malignancies. Timely reconstitution of antiviral CD8 T cells and their efficient recruitment to the lungs is crucial for preventing interstitial pneumonia, the most severe disease manifestation of CMV in HCT recipients. Here, we review recent work in a murine model, implicating mast cells (MC) in the control of pulmonary infection. Murine CMV (mCMV) productively infects MC in vivo and triggers their degranulation, resulting in the release of the CC chemokine ligand 5 (CCL5) that attracts CD8 T cells to infiltrate infected tissues. Comparing infection of MC-sufficient C57BL/6 mice and congenic MC-deficient Kit (W-sh/W-sh) "sash" mutants revealed an inverse relation between the number of lung-infiltrating CD8 T cells and viral burden in the lungs. Specifically, reduced lung infiltration by CD8 T cells in "sash" mutants was associated with an impaired infection control. The causal, though indirect, involvement of MC in antiviral control was confirmed by reversion of the deficiency phenotype in "sash" mutants reconstituted with MC. These recent findings predict that efficient MC reconstitution facilitates the control of CMV infection also in immunocompromised HCT recipients. PMID:25648117

  15. Pathological changes of cochlear in deaf mice at different time after mouse cytomegalovirus infection

    PubMed Central

    Tian, Yongyuan; Liu, Xinguo; Liu, Hongjian; Xing, Jinyan

    2015-01-01

    Objective: This study aims to observe the pathological changes of inner ear in deaf mice at different time after mouse cytomegalovirus infection. Methods: A total of 60 BALB/C mice were divided into 2 groups randomly: model group (A) and control group (B). In model group, 10 μl of MCMV was injected into the brain of each mouse while 10 μl of physiological saline was injected in control group. 10 cochlear samples were taken from 5 mice selected from each group randomly after infection for 1, 3, 5, 7, 14 and 21 days respectively. They were detected with PCR and HE staining methods. Auditory brain stem response was determined. The apoptosis of spiral ganglion (SGN) cells was detected by apoptosis assay kit. The levels of Bcl-2 and Bax were detected by RT-PCR and western blotting methods. Results: In group A, PCR results were negative after infection for 1 day, they were positive after infection for 3 days to 21 days. In group B, PCR results were negative in the experimental period. Compared with group B, ABR I wave latency and threshold increased while ABR I wave decreased in group A. There were no obvious hyperemia and inflammatory cells infiltration in group B, In group A, hemorrhage of scala tympani and scala vestibule appeared and reached highest peak after infection for 3 days accompanied by inflammatory cell infiltration; the vestibular membrane thickened after infection for 5 days; cell gap of SGN cells widened, arranged more sparsely with cell edema after infection for 7 days accompanied by infiltration of plasma cells; fibroblast proliferation and fibrosis appeared after infection for 14 days. Conclusions: MCMV infection occurred in cochlear after MCMV infection for 3 days and could sustain, the continues pathological changes of inner will bring difficulties to the treatment of CMV deafness, further studies on the specific mechanism of SGN changes caused by CMV infection will provide an important target for the treatment of CMV deafness. PMID:26221258

  16. Knowledge and practices of obstetricians and gynecologists regarding cytomegalovirus infection during pregnancy--United States, 2007.

    PubMed

    2008-01-25

    In the United States, congenital cytomegalovirus (CMV) infection occurs in approximately 1 in 150 live births, leading to permanent disabilities (e.g., hearing loss, vision loss, and cognitive impairment) in approximately 1 in 750 live-born children. A common mode of CMV transmission to a pregnant woman is through close contact with infected bodily fluids such as urine or saliva, especially from young children. Because no vaccine is available and treatment options are limited, renewed attention has been given to prevention of CMV infections among pregnant women through traditional infection-control practices, such as good hand hygiene. These practices have been encouraged by organizations such as CDC and the American College of Obstetricians and Gynecologists (ACOG), which recommend that obstetricians and gynecologists (OB/GYNs) counsel women on careful handling of potentially CMV-infected articles, such as diapers, and thorough hand washing after close contact with young children. Despite this increased emphasis on avoiding infection during pregnancy, few women are aware of CMV infection and how it can be prevented. During March-May 2007, ACOG surveyed a national sample of OB/GYNs to assess their knowledge and practices regarding CMV infection prevention. This report describes the results of that survey, which indicated that fewer than half (44%) of OB/GYNs surveyed reported counseling their patients about preventing CMV infection. These results emphasize the need for additional training of OB/GYNs regarding CMV infection prevention and for a better understanding of the reasons that physician knowledge regarding CMV transmission might not result in patient counseling. PMID:18219267

  17. Human cytomegalovirus gene expression in long-term infected glioma stem cells.

    PubMed

    Fiallos, Estefania; Judkins, Jonathon; Matlaf, Lisa; Prichard, Mark; Dittmer, Dirk; Cobbs, Charles; Soroceanu, Liliana

    2014-01-01

    The most common adult primary brain tumor, glioblastoma (GBM), is characterized by fifteen months median patient survival and has no clear etiology. We and others have identified the presence of human cytomegalovirus (HCMV) gene products endogenously expressed in GBM tissue and primary cells, with a subset of viral genes being consistently expressed in most samples. Among these viral genes, several have important oncomodulatory properties, regulating tumor stemness, proliferation, immune evasion, invasion and angiogenesis. These findings lead us to hypothesize that a specific HCMV gene signature may be associated with GBM pathogenesis. To investigate this hypothesis, we used glioma cell lines and primary glioma stem-like cells (GSC) infected with clinical and laboratory HCMV strains and measured relative viral gene expression levels along several time points up to 15 weeks post-infection. While HCMV gene expression was detected in several infected glioma lines through week 5 post-infection, only HCMV-infected GSC expressed viral gene products 15 weeks post-infection. Efficiency of infection across time was higher in GSC compared to cell lines. Importantly, HCMV-infected GSC outlived their uninfected counterparts, and this extended survival was paralleled by increased tumorsphere frequency and upregulation of stemness regulators, such as SOX2, p-STAT3, and BMX (a novel HCMV target identified in this study). Interleukin 6 (IL-6) treatment significantly upregulated HCMV gene expression in long-term infected glioma cultures, suggesting that pro-inflammatory signaling in the tumor milieu may further augment HCMV gene expression and subsequent tumor progression driven by viral-induced cellular signaling. Together, our data support a critical role for long-term, low-level HCMV infection in promoting survival, stemness, and proliferation of GSC that could significantly contribute to GBM pathogenesis. PMID:25549333

  18. Role of Cytomegalovirus (CMV) IgG Avidity Testing in Diagnosing Primary CMV Infection during Pregnancy

    PubMed Central

    Lapé-Nixon, Mary

    2014-01-01

    The risk of intrauterine transmission of cytomegalovirus (CMV) during pregnancy is much greater for women who contract primary CMV infection after conception than for women with evidence of infection (circulating CMV antibodies) before conception. Thus, laboratory tests that aid in the identification of recent primary CMV infection are important tools for managing the care of pregnant women suspected of having been exposed to CMV. CMV IgM detection is a sensitive marker of primary CMV infection, but its specificity is poor because CMV IgM is also produced during viral reactivation and persists following primary infection in some individuals. Studies conducted over the last 20 years convincingly demonstrate that measurement of CMV IgG avidity is both a sensitive and a specific method for identifying pregnant women with recent primary CMV infection and thus at increased risk for vertical CMV transmission. IgG avidity is defined as the strength with which IgG binds to antigenic epitopes expressed by a given protein; it matures gradually during the 6 months following primary infection. Low CMV IgG avidity is an accurate indicator of primary infection within the preceding 3 to 4 months, whereas high avidity excludes primary infection within the preceding 3 months. In this minireview, we summarize published data demonstrating the clinical utility of CMV IgG avidity results for estimating time since primary infection in pregnant women, describe commercially available CMV IgG avidity assays, and discuss some of the issues and controversies surrounding CMV IgG avidity testing during pregnancy. PMID:25165026

  19. Detection of CMV DNA in the perilymph of a 6-year-old boy with congenital cytomegalovirus infection.

    PubMed

    Foulon, Ina; Soetens, Oriane; Vleurinck, Leen; Gordts, Frans; Leus, Astrid; Naessens, Anne

    2016-06-01

    We present the case of a 6-year-old boy who received a cochlear implant for profound sensorineural hearing loss after being born with cytomegalovirus (CMV) infection. Even after 6 years, CMV DNA was still found in the perilymph of the cochlea. Our case shows that CMV DNA can be present in the cochlea years after congenital CMV infection, and it can explain why progressive and/or late-onset hearing loss occurs in these children. PMID:27304443

  20. Human Cytomegalovirus Promotes Survival of Infected Monocytes via a Distinct Temporal Regulation of Cellular Bcl-2 Family Proteins

    PubMed Central

    Collins-McMillen, Donna; Kim, Jung Heon; Nogalski, Maciej T.; Stevenson, Emily V.; Caskey, Joshua R.; Cieply, Stephen J.

    2015-01-01

    ABSTRACT Monocytes play a key role in the hematogenous dissemination of human cytomegalovirus (HCMV) to target organ systems. To infect monocytes and reprogram them to deliver infectious virus, HCMV must overcome biological obstacles, including the short life span of monocytes and their antiviral proapoptotic response to infection. We have shown that virally induced upregulation of cellular Mcl-1 promotes early survival of HCMV-infected monocytes, allowing cells to overcome an early apoptotic checkpoint at around 48 h postinfection (hpi). Here, we demonstrate an HCMV-dependent shift from Mcl-1 as the primary antiapoptotic player to the related protein, Bcl-2, later during infection. Bcl-2 was upregulated in HCMV-infected monocytes beginning at 48 hpi. Treatment with the Bcl-2 antagonist ABT-199 only reduced the prosurvival effects of HCMV in target monocytes beginning at 48 hpi, suggesting that Mcl-1 controls survival prior to 48 hpi, while Bcl-2 promotes survival after 48 hpi. Although Bcl-2 was upregulated following viral binding/signaling through cellular integrins (compared to Mcl-1, which is upregulated through binding/activation of epidermal growth factor receptor [EGFR]), it functioned similarly to Mcl-1, adopting the early role of Mcl-1 in preventing caspase-3 cleavage/activation. This distinct, HCMV-induced shift from Mcl-1 to Bcl-2 occurs in response to a cellular upregulation of proapoptotic Bax, as small interfering RNA (siRNA)-mediated knockdown of Bax reduced the upregulation of Bcl-2 in infected monocytes and rescued the cells from the apoptotic effects of Bcl-2 inhibition. Our data demonstrate a distinct survival strategy whereby HCMV induces a biphasic regulation of cellular Bcl-2 proteins to promote host cell survival, leading to viral dissemination and the establishment of persistent HCMV infection. IMPORTANCE Hematogenous dissemination of HCMV via infected monocytes is a crucial component of the viral survival strategy and is required for the

  1. Cytomegalovirus Infection among Infants in California Neonatal Intensive Care Units, 2005–2010

    PubMed Central

    Lanzieri, Tatiana M.; Bialek, Stephanie R.; Bennett, Mihoko V.; Gould, Jeffrey B.

    2016-01-01

    Aim Assess the burden of congenital and perinatal cytomegalovirus (CMV) disease among infants hospitalized in neonatal intensive care units (NICUs). Methods CMV infection was defined as a report of positive CMV viral culture or PCR at any time since birth in an infant hospitalized in a NICU reporting to California Perinatal Quality Care Collaborative during 2005–2010. Results 156 (1.7 per 1000) infants were reported with CMV infection, representing an estimated 5% of the expected number of live births with symptomatic CMV disease. Prevalence was higher among infants with younger gestational ages and lower birth weights. Infants with CMV infection had significantly longer hospital stays; 14 (9%) died. Conclusions Reported prevalence of CMV infection in NICUs represents a fraction of total expected disease burden from CMV in the newborn period, likely resulting from underdiagnosis and milder symptomatic cases that do not require NICU care. More complete ascertainment of infants with congenital CMV infection that would benefit from antiviral treatment may reduce the burden of CMV disease in this population. PMID:24334425

  2. Dynamics of the NK-cell subset redistribution induced by cytomegalovirus infection in preterm infants.

    PubMed

    Noyola, Daniel E; Alarcón, Ana; Noguera-Julian, Antoni; Muntasell, Aura; Muñoz-Almagro, Carmen; García, Jordi; Mur, Antonio; Fortuny, Claudia; López-Botet, Miguel

    2015-03-01

    Human cytomegalovirus (HCMV) infection promotes an expansion of NK-cells expressing the CD94/NKG2C receptor. We prospectively monitored the effects of HCMV on the NK-cell receptor (NKG2C, NKG2A, KIR, LILRB1) distribution in preterm infants. As compared to non-infected moderately preterm newborns (n=19, gestational age: 32-37 weeks), very preterm infants (n=5, gestational age: <32 weeks) suffering symptomatic postnatal HCMV infection displayed increased numbers of NKG2C+, KIR+ NK-cells, encompassed by a reduction of NKG2A+ NK-cells. A similar profile was observed in HCMV-negative newborns (n=4) with asymptomatic infection, during follow-up at ~4 and 10 months of age. Of note, viremia remained detectable in three symptomatic cases at ~10 months despite the persistent expansion of NKG2C+ NK-cells. Our study provides original insights on the dynamics of the imprint exerted by primary HCMV infection on the NK-cell compartment, revealing that the expansion of NKG2C+ NK-cells may be insufficient to control viral replication in very preterm infants. PMID:25636568

  3. Specific serum immunoglobulin D, detected by antibody capture enzyme-linked immunosorbent assay (ELISA), in cytomegalovirus infection.

    PubMed Central

    Mortensen, J; Nielsen, S L; Sørensen, I; Andersen, H K

    1989-01-01

    An antibody capture enzyme-linked immunosorbent assay (ELISA) was developed for the detection of immunoglobulin D (IgD) antibodies to cytomegalovirus (CMV) in sera from blood donors and various groups of patients infected with CMV. This method has previously been found especially valuable in detecting specific antibodies of the IgM, IgE, IgA and IgG class in patients with CMV infection. Specific CMV IgD antibodies were found in 37% of CMV seropositive blood donors and in 47 (88%) of the 53 patients investigated, including bone marrow transplant and renal allograft transplant patients, patients with CMV mononucleosis, neonates with CMV infection and AIDS patients with CMV infection. The highest IgD reactivity was found in patients having either a primary post-transplant CMV infection or CMV mononucleosis. The IgD reactivity in patients with AIDS and in neonates was low. It was also found that in the acute phase of CMV infection the development of CMV antibodies of the IgD class was similar to the development of antibodies of the other classes. The maintenance of IgD activity in some patients together with the presence of CMV IgD antibodies in a great proportion of the blood donors indicates that the development of CMV IgD antibodies resembles that of the IgG class. Determination of specific IgD antibodies offered no advantage over determination of specific antibodies of the IgM, IgE and IgA classes in the diagnosis of CMV infection. PMID:2539278

  4. Immunobiology of herpes simplex virus and cytomegalovirus infections of the fetus and newborn

    PubMed Central

    Muller, William J.; Jones, Cheryl A.; Koelle, David M.

    2010-01-01

    Immunologic “immaturity” is often blamed for the increased susceptibility of newborn humans to infection, but the precise mechanisms and details of immunologic development remain somewhat obscure. Herpes simplex virus (HSV) and cytomegalovirus (CMV) are two of the more common severe infectious agents of the fetal and newborn periods. HSV infection in the newborn most commonly occurs after exposure to the virus during delivery, and can lead to a spectrum of clinical disease ranging from isolated skin-eye-mucous membrane infection to severe disseminated multiorgan disease, often including encephalitis. In contrast to HSV, clinically severe CMV infections early in life are usually acquired during the intrauterine period. These infections can result in a range of clinical disease, including hearing loss and neurodevelopmental delay. However, term newborns infected with CMV after delivery are generally asymptomatic, and older children and adults often acquire infection with HSV or CMV with either no or mild clinical symptoms. The reasons for these widely variable clinical presentations are not completely understood, but likely relate to developmental differences in immune responses. This review summarizes recent human and animal studies of the immunologic response of the fetus and newborn to these two infections, in comparison to the responses of older children and adults. The immunologic defense of the newborn against each virus is considered under the broader categories of (i) the placental barrier to infection, (ii) skin and mucosal barriers (including antimicrobial peptides), (iii) innate responses, (iv) humoral responses, and (v) cellular responses. A specific focus is made on recent studies of innate and cellular immunity to HSV and CMV. PMID:20467462

  5. Poly(A) binding protein abundance regulates eukaryotic translation initiation factor 4F assembly in human cytomegalovirus-infected cells.

    PubMed

    McKinney, Caleb; Perez, Cesar; Mohr, Ian

    2012-04-10

    By commandeering cellular translation initiation factors, or destroying those dispensable for viral mRNA translation, viruses often suppress host protein synthesis. In contrast, cellular protein synthesis proceeds in human cytomegalovirus (HCMV)-infected cells, forcing viral and cellular mRNAs to compete for limiting translation initiation factors. Curiously, inactivating the host translational repressor 4E-BP1 in HCMV-infected cells stimulates synthesis of the cellular poly(A) binding protein (PABP), significantly increasing PABP abundance. Here, we establish that new PABP synthesis is translationally controlled by the HCMV-encoded UL38 mammalian target of rapamycin complex 1-activator. The 5' UTR within the mRNA encoding PABP contains a terminal oligopyrimidine (TOP) element found in mRNAs, the translation of which is stimulated in response to mitogenic, growth, and nutritional stimuli, and proteins encoded by TOP-containing mRNAs accumulated in HCMV-infected cells. Furthermore, UL38 expression was necessary and sufficient to regulate expression of a PABP TOP-containing reporter. Remarkably, preventing the rise in PABP abundance by RNAi impaired eIF4E binding to eIF4G, thereby reducing assembly of the multisubunit initiation factor eIF4F, viral protein production, and replication. This finding demonstrates that viruses can increase host translation initiation factor concentration to foster their replication and defines a unique mechanism whereby control of PABP abundance regulates eIF4F assembly. PMID:22431630

  6. Clinical relevance of the plasma load of cytomegalovirus in patients infected with HIV--a survival analysis.

    PubMed

    Aramă, Victoria; Mihăilescu, Raluca; Rădulescu, Mihaela; Aramă, Sorin Ştefan; Streinu-Cercel, Adrian; Youle, Mike

    2014-11-01

    To investigate whether asymptomatic cytomegalovirus (CMV) viraemia impact the course of human immunodeficiency virus (HIV) infection, this study evaluated the effect of CMV replication on progression of newly-diagnosed HIV infected individuals towards AIDS events and death. In a 3-year prospective study on co-infected patients, clinical, immunological, and virological tests were performed in a national reference hospital quarterly. CMV viraemia was quantified by RoboGene® HCMV DNA Quantification Kit (Analytik Jena, Germany), on ABI Prism® 7000 Sequence Detection System (Applied Biosystems, USA). One hundred and five patients were enrolled with a balanced sex distribution and a median age of 30.7 years. Median CD4(+) cell count at enrollment was 164/mm(3) and median HIV RNA 4.6 log10 copies/ml. Detectable CMV viraemia was found in 25.7% of the patients. Kaplan-Meier analysis showed progression of HIV infection to be significantly increased in those with active CMV replication and/or low CD4(+) cell count. Cox regression indicated the risk of developing new AIDS events was 2.6 times greater in patients with detectable CMV viraemia versus those without (CI95% 1-6.6; P = 0.04). Also in multivariate analysis, the overall risk of progression to AIDS events or death was 3-fold higher in those with detectable CMV viraemia (CI95% 1.3-6.7; P = 0.008) and 2.3-fold higher if CD4(+) cell count was below 100/mm(3) (CI95% 1-5.1; P = 0.04). In these young Romanian HIV-seropositives, active CMV replication increased morbidity, even when treated with combination antiretroviral therapy. Further studies are needed to evaluate if serial quantitative CMV-DNA levels might correlate with non-infectious inflammation-related risks in patients with HIV and active CMV infection. PMID:25087866

  7. Genetic mechanism associated with congenital cytomegalovirus infection and analysis of effects of the infection on pregnancy outcome.

    PubMed

    Li, J M; Zhang, H F; Zhang, X Q; Huang, G L; Huang, H Z; Yu, W W

    2015-01-01

    We aimed to compare the diagnostic value of various detection methods for cytomegalovirus (CMV) infection, to investigate the genetic mechanism associated with CMV infection in pregnant women, and to analyze the risk of sequelae development in fetuses with CMV infection. A total of 300 participants who had the same immunosuppressive regimen and received preemptive therapy for CMV infection were prospectively enrolled in this study; they included 289 vaccine trial participants. The gB-absorbed CMV IgG assay was performed for each vaccine trial participant. The healthy women were divided into 2 groups, and amniotic fluids were collected from them at 15-18 weeks of gestation to test for CMV seropositivity before conception by using IgM specific antibodies, CMV-DNA, and IgG analysis. In 104 cases, cord blood sera and urine specimens were also collected from the infants and examined. The sensitivity and specificity of immediate-early messenger RNA and pp67 (late) messenger RNA detection by the nucleic acid sequence-based amplification technique was comparable to those of virus isolation and PCR. Furthermore, an association between single nucleotide polymorphisms in the TLR-2 gene and congenital CMV infection was observed and confirmed. Moreover, CMV infection during early pregnancy has been shown to have a much more severe effect on the pregnancy outcome compared to infection during later stages of pregnancy. PMID:26535638

  8. Ganciclovir-Resistant Cytomegalovirus Infection in a Kidney Transplant Recipient Successfully Treated with Foscarnet and Everolimus.

    PubMed

    Menghi, Viola; Comai, Giorgia; Baraldi, Olga; Liviano D'Arcangelo, Giovanni; Lazzarotto, Tiziana; La Manna, Gaetano

    2016-01-01

    Cytomegalovirus (CMV) infection remains a major cause of morbidity, graft failure, and death in kidney transplant recipients. We describe a case of a 53-year-old CMV-seronegative man who underwent renal transplant from a CMV-positive donor and who developed ganciclovir- (GCV-) resistant CMV infection. Foscarnet was started while immunosuppressive therapy was modified with the introduction of everolimus minimizing tacrolimus dosage. Only two weeks after the start of this treatment regimen was the patient's viral load negative. At two-year follow-up the patient has no clinical or laboratory signs of CMV infection and a good and stable renal function or graft survival. In our case, administration of an mTOR inhibitor combined with foscarnet led to rapid and persistent viral clearance without compromising short- and medium-term graft function. This combination therapy supports the need for the kidney transplant community to individualize a target therapy for each type of GCV-resistant CMV infection. PMID:26942027

  9. Ganciclovir-Resistant Cytomegalovirus Infection in a Kidney Transplant Recipient Successfully Treated with Foscarnet and Everolimus

    PubMed Central

    Menghi, Viola; Comai, Giorgia; Baraldi, Olga; Liviano D'Arcangelo, Giovanni; Lazzarotto, Tiziana; La Manna, Gaetano

    2016-01-01

    Cytomegalovirus (CMV) infection remains a major cause of morbidity, graft failure, and death in kidney transplant recipients. We describe a case of a 53-year-old CMV-seronegative man who underwent renal transplant from a CMV-positive donor and who developed ganciclovir- (GCV-) resistant CMV infection. Foscarnet was started while immunosuppressive therapy was modified with the introduction of everolimus minimizing tacrolimus dosage. Only two weeks after the start of this treatment regimen was the patient's viral load negative. At two-year follow-up the patient has no clinical or laboratory signs of CMV infection and a good and stable renal function or graft survival. In our case, administration of an mTOR inhibitor combined with foscarnet led to rapid and persistent viral clearance without compromising short- and medium-term graft function. This combination therapy supports the need for the kidney transplant community to individualize a target therapy for each type of GCV-resistant CMV infection. PMID:26942027

  10. Is there any association of extra hepatic biliary atresia with cytomegalovirus or other infections?

    PubMed

    Soomro, Ghous Bukhsh; Abbas, Zaigham; Hassan, Mujahid; Luck, Nasir; Memon, Yousuf; Khan, Abdaal Wasim

    2011-03-01

    The objective of this study was to find any association of extrahepatic biliary atresia (EHBA) with a possible infectious etiology. Infants diagnosed to have EHBA were tested by blood PCR for cytomegalovirus (CMV), Ebstein-Barr virus, HBsAg, anti-HCV and IgM antibodies for CMV, toxoplasma, rubella, and herpes infections. Thirty-three infants of EHBA were included in the study, male 22, median age when diagnosed 2.5 months (range 1.0-5.0 months). On examination pallor, oedema and hepatosplenomegaly were seen in all and ascites and microcephaly in 19 (57.6%). Centile height and weight were 50th in 23 and 25th in 10. Persistent CMV infection documented by PCR was present in 14 (42%) patients. Eleven of these also had positive CMV IgM antibodies. No other above mentioned infections could be detected in our patients of EHBA. Our data suggests that CMV infection may play a role in the pathogenesis and progression of EHBA. PMID:21465946

  11. Enhanced capacity of DNA repair in human cytomegalovirus-infected cells

    SciTech Connect

    Nishiyama, Y.; Rapp, F.

    1981-04-01

    Plaque formation in Vero cells by UV-irradiated herpes simplex virus was enhanced by infection with human cytomegalovirus (HCMV), UV irradiation, or treatment with methylmethanesulfonate. Preinfection of Vero cells with HCMV enhanced reactivation of UV-irradiated herpes simplex virus more significantly than did treatment with UV or methylmethanesulfonate alone. A similar enhancement by HCMV was observed in human embryonic fibroblasts, but not in xeroderma pigmentosum (XP12BE) cells. It was also found that HCMV infection enhanced hydroxyurea-resistant DNA synthesis induced by UV light or methylmethanesulfonate. Alkaline sucrose gradient sedimentation analysis revealed an enhanced rate of synthesis of all size classes of DNA in UV-irradiated HCMV-infected Vero cells. However, HCMV infection did not induce repairable lesions in cellular DNA and did not significantly inhibit host cell DNA synthesis, unlike UV or methylmethanesulfonate. These results indicate that HCMV enhanced DNA repair capacity in the host cells without producing detectable lesions in cellular DNA and without inhibiting DNA synthesis. This repair appeared to be error proof for UV-damaged herpes simplex virus DNA when tested with herpes simplex virus thymidine kinase-negative mutants.

  12. Excess apoptosis of mononuclear cells contributes to the depressed cytomegalovirus-specific immunity in HIV-infected patients on HAART

    SciTech Connect

    Weinberg, Adriana . E-mail: Adriana.Weinberg@uchsc.edu; Jesser, Renee D.; Edelstein, Charles L.; Bill, Jerome R.; Wohl, David A.

    2004-12-05

    HIV-infected patients on highly active antiretroviral therapy (HAART) have persistently decreased cytomegalovirus (CMV)-specific proliferative responses [lymphocyte proliferation assay (LPA)] in spite of increases in CD4+ T cell counts. Here we demonstrate an association between apoptosis of unstimulated peripheral blood mononuclear cells (uPBMC) and decreased CMV-LPA. HAART recipients had more apoptosis of uPBMC than controls when measured by caspases 3, 8, and 9 activities and by annexin V binding. Patients with undetectable HIV replication maintained significantly higher apoptosis of CD4+ and CD14+ cells compared to controls. CMV-LPA decreased with higher apoptosis of uPBMC in patients only. This association was independent of CD4+ cell counts or HIV replication. Furthermore, rescuing PBMC from apoptosis with crmA, but not with TRAIL- or Fas-pathway blocking agents or with other caspase inhibitors, increased CMV-LPA in HAART recipients. This effect was not observed in uninfected controls, further indicating that the down regulatory effect of apoptosis on cell-mediated immunity (CMI) was specifically associated with the HIV-infected status.

  13. THY-1 Cell Surface Antigen (CD90) Has an Important Role in the Initial Stage of Human Cytomegalovirus Infection

    PubMed Central

    Li, Qingxue; Wilkie, Adrian R.; Weller, Melodie; Liu, Xueqiao; Cohen, Jeffrey I.

    2015-01-01

    Human cytomegalovirus (HCMV) infects about 50% of the US population, is the leading infectious cause of birth defects, and is considered the most important infectious agent in transplant recipients. The virus infects many cell types in vivo and in vitro. While previous studies have identified several cellular proteins that may function at early steps of infection in a cell type dependent manner, the mechanism of virus entry is still poorly understood. Using a computational biology approach, correlating gene expression with virus infectivity in 54 cell lines, we identified THY-1 as a putative host determinant for HCMV infection in these cells. With a series of loss-of-function, gain-of-function and protein-protein interaction analyses, we found that THY-1 mediates HCMV infection at the entry step and is important for infection that occurs at a low m.o.i. THY-1 antibody that bound to the cell surface blocked HCMV during the initial 60 minutes of infection in a dose-dependent manner. Down-regulation of THY-1 with siRNA impaired infectivity occurred during the initial 60 minutes of inoculation. Both THY-1 antibody and siRNA inhibited HCMV-induced activation of the PI3-K/Akt pathway required for entry. Soluble THY-1 protein blocked HCMV infection during, but not after, virus internalization. Expression of exogenous THY-1 enhanced entry in cells expressing low levels of the protein. THY-1 interacted with HCMV gB and gH and may form a complex important for entry. However, since gB and gH have previously been shown to interact, it is uncertain if THY-1 directly binds to both of these proteins. Prior observations that THY-1 (a) interacts with αVβ3 integrin and recruits paxillin (implicated in HCMV entry), (b) regulates leukocyte extravasation (critical for HCMV viremia), and (c) is expressed on many cells targeted for HCMV infection including epithelial and endothelial cells, fibroblast, and CD34+/CD38- stem cells, all support a role for THY-1 as an HCMV entry mediator in

  14. THY-1 Cell Surface Antigen (CD90) Has an Important Role in the Initial Stage of Human Cytomegalovirus Infection.

    PubMed

    Li, Qingxue; Wilkie, Adrian R; Weller, Melodie; Liu, Xueqiao; Cohen, Jeffrey I

    2015-07-01

    Human cytomegalovirus (HCMV) infects about 50% of the US population, is the leading infectious cause of birth defects, and is considered the most important infectious agent in transplant recipients. The virus infects many cell types in vivo and in vitro. While previous studies have identified several cellular proteins that may function at early steps of infection in a cell type dependent manner, the mechanism of virus entry is still poorly understood. Using a computational biology approach, correlating gene expression with virus infectivity in 54 cell lines, we identified THY-1 as a putative host determinant for HCMV infection in these cells. With a series of loss-of-function, gain-of-function and protein-protein interaction analyses, we found that THY-1 mediates HCMV infection at the entry step and is important for infection that occurs at a low m.o.i. THY-1 antibody that bound to the cell surface blocked HCMV during the initial 60 minutes of infection in a dose-dependent manner. Down-regulation of THY-1 with siRNA impaired infectivity occurred during the initial 60 minutes of inoculation. Both THY-1 antibody and siRNA inhibited HCMV-induced activation of the PI3-K/Akt pathway required for entry. Soluble THY-1 protein blocked HCMV infection during, but not after, virus internalization. Expression of exogenous THY-1 enhanced entry in cells expressing low levels of the protein. THY-1 interacted with HCMV gB and gH and may form a complex important for entry. However, since gB and gH have previously been shown to interact, it is uncertain if THY-1 directly binds to both of these proteins. Prior observations that THY-1 (a) interacts with αVβ3 integrin and recruits paxillin (implicated in HCMV entry), (b) regulates leukocyte extravasation (critical for HCMV viremia), and (c) is expressed on many cells targeted for HCMV infection including epithelial and endothelial cells, fibroblast, and CD34+/CD38- stem cells, all support a role for THY-1 as an HCMV entry mediator in

  15. [Optimisation of retrospective diagnosis of cytomegalovirus congenital infection from dried blood spots].

    PubMed

    Vauloup-Fellous, C; Dubreuil, P; Grangeot-Keros, L

    2006-12-01

    Out of the 90% of cytomegalovirus (CMV) congenitally infected children that are asymptomatic at birth, 5 to 15% will later develop complications, mainly neurodevelopmental defects and/or deafness. Unfortunately, after the first 2 weeks of life, usual diagnostic techniques for CMV detection (viral culture and serology) are useless to differentiate congenital infection from post-natal acquired infection, whereas detection of viral DNA from dried blood spots (DBS; Guthrie cards), systematically collected from all newborns in the first days of life, has been described for late diagnosis of CMV congenital infection. The aim of our study was to choose and optimise a viral DNA extraction method from DBS and to study if CMV DNA detection is reliable when DBS are stored for 1 year at room temperature or 2 months at 37 degrees C. 10 reference cards (blood collected from CMV seronegative newborns (IgG/IgM negative) were "infected" with serial dilutions of virus and spotted on Guthrie cards) were tested. 3 extraction methods were evaluated, products of PCR were analyzes by agarose gel electrophoresis and quantification of CMV from DBS was also performed. Analysis of the results obtained from reference cards showed higher sensitivity of phenol/chloroform extraction following treatment with proteinase K, compared to heat extraction in cell culture medium or extraction with a commercial kit. We did not observe quantitative loss of viral DNA after 1 year storage at room temperature. CMV DNA detection from Guthrie cards could become a very useful tool for retrospective diagnosis of congenital CMV infection when sequelae are diagnosed in the first years of life. We are pursuing this study with DBS from congenitally infected children. PMID:17027198

  16. Antagonistic Determinants Controlling Replicative and Latent States of Human Cytomegalovirus Infection

    PubMed Central

    Umashankar, Mahadevaiah; Rak, Michael; Bughio, Farah; Zagallo, Patricia; Caviness, Katie

    2014-01-01

    ABSTRACT The mechanisms by which viruses persist and particularly those by which viruses actively contribute to their own latency have been elusive. Here we report the existence of opposing functions encoded by genes within a polycistronic locus of the human cytomegalovirus (HCMV) genome that regulate cell type-dependent viral fates: replication and latency. The locus, referred to as the UL133-UL138 (UL133/8) locus, encodes four proteins, pUL133, pUL135, pUL136, and pUL138. As part of the ULb′ region of the genome, the UL133/8 locus is lost upon serial passage of clinical strains of HCMV in cultured fibroblasts and is therefore considered dispensable for replication in this context. Strikingly, we could not reconstitute infection in permissive fibroblasts from bacterial artificial chromosome clones of the HCMV genome where UL135 alone was disrupted. The loss of UL135 resulted in complex phenotypes and could ultimately be overcome by infection at high multiplicities. The requirement for UL135 but not the entire locus led us to hypothesize that another gene in this locus suppressed virus replication in the absence of UL135. The defect associated with the loss of UL135 was largely rescued by the additional disruption of the UL138 latency determinant, indicating a requirement for UL135 for virus replication when UL138 is expressed. In the CD34+ hematopoietic progenitor model of latency, viruses lacking only UL135 were defective for viral genome amplification and reactivation. Taken together, these data indicate that UL135 and UL138 comprise a molecular switch whereby UL135 is required to overcome UL138-mediated suppression of virus replication to balance states of latency and reactivation. IMPORTANCE Mechanisms by which viruses persist in their host remain one of the most poorly understood phenomena in virology. Herpesviruses, including HCMV, persist in an incurable, latent state that has profound implications for immunocompromised individuals, including transplant

  17. Awareness of Cytomegalovirus Infection among Pregnant Women in Geneva, Switzerland: A Cross-sectional Study

    PubMed Central

    Willame, Alexia; Blanchard-Rohner, Geraldine; Combescure, Christophe; Irion, Olivier; Posfay-Barbe, Klara; Martinez de Tejada, Begoña

    2015-01-01

    Background: Cytomegalovirus (CMV) is the most frequent cause of congenital infection and commonly associated with sensorineural deficit. At present, there is neither prophylaxis nor treatment during pregnancy. The objective of this study was to evaluate the level of awareness regarding CMV infection and its consequences in women delivering at the University of Geneva Hospitals (Geneva, Switzerland). Methods: The study consisted of a validated questionnaire completed by women in the immediate postpartum period. Results: The questionnaire was completed by 59% (314/528) of delivering women. Only 39% (123/314) knew about CMV and 19.7% (62/314) had received information about preventive measures. Women were more aware about other congenital diseases, such as toxoplasmosis (87%); human immunodeficiency virus (99%); syphilis (85.5%); rubella (92.3%); and group B Streptococcus (63%). Factors associated with CMV awareness were Swiss nationality, high education level, employment in health care or with children, and being followed by an obstetrician. Regarding quality of information, few were aware of the main CMV complications (deafness, 25.2%; mental retardation, 34.5%). Among those informed about CMV, most (74.6%) knew about preventive measures. Among these, 82.5% thought that these were easily applicable. Conclusions: Most women are unaware of CMV infection and its potential risks during pregnancy. It is crucial to improve CMV information given to pregnant women to prevent the risks for the fetus/newborn. PMID:26633451

  18. Systematic review of the birth prevalence of congenital cytomegalovirus infection in developing countries

    PubMed Central

    Lanzieri, Tatiana M.; Dollard, Sheila C.; Bialek, Stephanie R.; Grosse, Scott D.

    2016-01-01

    Summary Background Congenital cytomegalovirus (CMV) infection is the leading infectious cause of congenital hearing loss and neurodevelopmental disability in developed countries. Information on congenital CMV infection in developing countries appears to be lacking. Methods We conducted a systematic literature review to identify studies from developing countries with population-based samples of at least 300 infants that used laboratory methods established as reliable for the diagnosis of congenital CMV infection. Results Most studies were excluded due to biased samples or inadequate diagnostic methods; consequently the search identified just 11 studies that were from Africa, Asia, and Latin America. The number of newborns tested ranged from 317 to 12 195. Maternal CMV seroprevalence ranged from 84% to 100%. CMV birth prevalence varied from 0.6% to 6.1%. CMV-associated impairments were not documented in most studies. Conclusions Birth prevalence ranges were higher than for Europe and North America, as expected based on the higher maternal CMV seroprevalence. With very limited data available on sequelae, the disease burden of congenital CMV in developing countries remains largely unknown at this time. PMID:24631522

  19. Virological and Immunological Characteristics of Human Cytomegalovirus Infection Associated With Alzheimer Disease

    PubMed Central

    Lurain, Nell S.; Hanson, Barbara A.; Martinson, Jeffrey; Leurgans, Sue E.; Landay, Alan L.; Bennett, David A.; Schneider, Julie A.

    2013-01-01

    Serum, cerebrospinal fluid (CSF), and cryopreserved lymphocytes from subjects in the Rush Alzheimer's Disease Center Religious Orders Study were analyzed for associations between cytomegalovirus (CMV) infection and clinical and pathological markers of Alzheimer disease. CMV antibody levels were associated with neurofibrillary tangles (NFTs). CSF interferon γ was only detected in seropositive subjects and was significantly associated with NFTs. The percentage of senescent T cells (CD4+ or CD8+CD28−CD57+) was significantly higher for CMV-seropositive as compared to CMV-seronegative subjects and was marginally associated with the pathologic diagnosis of Alzheimer disease (CD4+) or amyloid-β (CD8+). Immunocytochemical analysis showed induction of amyloid-β in human foreskin fibroblasts (HFFs) infected with each of 3 clinical CMV strains. In the same subjects, there was no association of herpes simplex virus type 1 (HSV-1) antibody levels with CMV antibody levels or clinical or pathological markers of Alzheimer disease. HSV-1 infection of HFFs did not induce amyloid-β. These data support an association between CMV and the development of Alzheimer disease. PMID:23661800

  20. Impact of Persistent Cytomegalovirus Infection on Dynamic Changes in Human Immune System Profile

    PubMed Central

    Vescovini, Rosanna; Telera, Anna Rita; Pedrazzoni, Mario; Abbate, Barbara; Rossetti, Pietro; Verzicco, Ignazio; Arcangeletti, Maria Cristina; Medici, Maria Cristina; Calderaro, Adriana; Volpi, Riccardo; Sansoni, Paolo; Fagnoni, Francesco Fausto

    2016-01-01

    Human cytomegalovirus (HCMV) imprints the immune system after primary infection, however its effect during chronic infection still needs to be deciphered. In this study we report the variation of blood cell count along with anti-HCMV IgG and T cell responses to pp-65 and IE-1 antigens, that occurred after an interval of five years in a cohort of 25 seropositive healthy adults. We found increased anti-viral IgG antibody responses and intracellular interferon-gamma secreting CD8+ T cell responses to pp-65: a result consistent with memory inflation. With the only exception of shortage in naive CD8+ T cells most memory T cell subsets as well as total CD8+ T cells, T cells, lymphocytes, monocytes and leukocytes had increased. By contrast, none of the cell types tested were found to have increased in 14 subjects stably seronegative. Rather, in addition to a shortage in naive CD8+ T cells, also memory T cell subsets and most other cell types decreased, either in a statistically significant or non-significant manner. The trend of T cell pool representation with regard to CD4/CD8 ratio was in the opposing directions depending on HCMV serology. Globally, this study demonstrates different dynamic changes of most blood cell types depending on presence or absence of HCMV infection. Therefore, HCMV plays a continual role in modulating homeostasis of blood T cells and a broader expanding effect on other cell populations of lymphoid and myeloid origin. PMID:26990192

  1. Congenital cytomegalovirus infection in fraternal twins: a longitudinal case study examining neurocognitive and neurobehavioral correlates.

    PubMed

    Llorente, Antolin M; Castillo, Christine L

    2012-01-01

    Cytomegalovirus (CMV) is the most ubiquitous member of the herpes virus family and is the leading cause of congenital (vertical) infection in newborns (Fowler, Stagno, & Pass, 2003; Llorente, Steigmeyer, Cooper, Rivers, & Gazley, 2011; Noyola et al., 2000; Steigmeyer & Llorente, 2010). CMV is related to the group of viruses capable of causing more pernicious infectious diseases, such as chicken pox (Santos de Barona, 1998). Although the virus generally remains dormant, individuals whose symptoms are clinically apparent often are dramatically affected. Common symptomatic characteristics of the virus include microcephaly, jaundice, liver-spleen infections, pneumonia, cardiac anomalies, chorioretinitis, vision loss, sensory-neural hearing loss, mental retardation, and mononucleosis (Demmler, 1991; Kashden, Frison, Fowler, Pass, & Boll, 1998; Noyola et al., 2000; Pass, 2005; Santos de Barona). The prognosis of individuals with CMV is highly variable, and the prognosis of individuals with congenital CMV can usually be determined based on the extent of infection at birth. The purpose of this investigation is to present longitudinal results of neuropsychological evaluation of two dizygotic twin sets (one twin of each set is asymptomatic CMV-positive and the other is uninfected) who were reared in the same environment. In addition, the present findings are discussed within the context of emerging murine and other animal analogues of CMV as well as within the extant CMV literature. PMID:23428280

  2. RAT CYTOMEGALOVIRUS INFECTION DEPLETES MHC II IN BONE MARROW DERIVED DENDRITIC CELLS

    PubMed Central

    Baca Jones, Carmen C.; Kreklywich, Craig N.; Messaoudi, Ilhem; Vomaske, Jennifer; McCartney, Erin; Orloff, Susan L.; Nelson, Jay A.; Streblow, Daniel N.

    2009-01-01

    While cytomegalovirus (CMV) infects and replicates in a multitude of cell types, the ability of the virus to replicate in antigen presenting cells (APCs) is believed to play a critical role in the viral dissemination and latency. CMV infection of APCs and manipulation of their function is an important area of investigation. CMV down regulation of MHC II is reportedly mediated by the HCMV proteins US2, US3, UL83, UL111a (vIL10) or through the induction of cellular IL10. In this study, we demonstrate that rat CMV (RCMV) significantly reduces MHC II expression by mechanisms that do not involve orthologues of the known HCMV genes nor by an increase in cellular IL10. Rat bone marrow derived dendritic cells (BMDC) were highly susceptible to infection with RCMV and a recombinant RCMV expressing eGFP. RCMV infection of BMDCs depleted both surface and intracellular MHC II to nearly undetectable levels as well as reduced surface expression of MHC I. The effect on MHC II only occurred in the infected GFP positive cells and is mediated by an immediate early or early viral gene product. Furthermore, treatment of uninfected immature DCs with virus-free conditioned supernatants from infected cells failed to down regulate MHC II. RCMV depletion of MHC II was sensitve to treatment with lysosomal inhibitors but not proteasomal inhibitors suggesting that the mechanism of RCMV mediated down-regulation of MHC II occurs through endocytic degradation. Since RCMV does not encode homologues of US2, US3, UL83 or UL111a, these data indicate a novel mechanism for RCMV depletion of MHC II. PMID:19349057

  3. Signaling Lymphocytic Activation Molecule Family Receptor Homologs in New World Monkey Cytomegaloviruses

    PubMed Central

    Pérez-Carmona, Natàlia; Farré, Domènec; Martínez-Vicente, Pablo; Terhorst, Cox; Engel, Pablo

    2015-01-01

    ABSTRACT Throughout evolution, large DNA viruses have been usurping genes from their hosts to equip themselves with proteins that restrain host immune defenses. Signaling lymphocytic activation molecule (SLAM) family (SLAMF) receptors are involved in the regulation of both innate and adaptive immunity, which occurs upon engagement with their ligands via homotypic or heterotypic interactions. Here we report a total of seven SLAMF genes encoded by the genomes of two cytomegalovirus (CMV) species, squirrel monkey CMV (SMCMV) and owl monkey CMV (OMCMV), that infect New World monkeys. Our results indicate that host genes were captured by retrotranscription at different stages of the CMV-host coevolution. The most recent acquisition led to S1 in SMCMV. S1 is a SLAMF6 homolog with an amino acid sequence identity of 97% to SLAMF6 in its ligand-binding N-terminal Ig domain. We demonstrate that S1 is a cell surface glycoprotein capable of binding to host SLAMF6. Furthermore, the OMCMV genome encodes A33, an LY9 (SLAMF3) homolog, and A43, a CD48 (SLAMF2) homolog, two soluble glycoproteins which recognize their respective cellular counterreceptors and thus are likely to be viral SLAMF decoy receptors. In addition, distinct copies of further divergent CD48 homologs were found to be encoded by both CMV genomes. Remarkably, all these molecules display a number of unique features, including cytoplasmic tails lacking characteristic SLAMF signaling motifs. Taken together, our findings indicate a novel immune evasion mechanism in which incorporation of host SLAMF receptors that retain their ligand-binding properties enables viruses to interfere with SLAMF functions and to supply themselves with convenient structural molds for expanding their immunomodulatory repertoires. IMPORTANCE The way in which viruses shape their genomes under the continual selective pressure exerted by the host immune system is central for their survival. Here, we report that New World monkey cytomegaloviruses

  4. Preliminary Evaluation of the Safety and Efficacy of Standard Intravenous Immunoglobulins in Pregnant Women with Primary Cytomegalovirus Infection

    PubMed Central

    Polilli, Ennio; D'Arcangelo, Francesca; Tracanna, Elisa; Clerico, Luigi; Savini, Vincenzo; D'Antonio, Francesco; Rosati, Maurizio; Manzoli, Lamberto; D'Antonio, Domenico; Nigro, Giovanni

    2012-01-01

    Hyperimmune globulins were reported to prevent and treat fetal cytomegalovirus (CMV) infection during pregnancy. Here, we report that infusions of standard human intravenous immunoglobulin significantly increase CMV IgG titers and avidity indexes in pregnant women, paving the way to their use for passive transfer of maternal CMV humoral immunity to fetuses. Preliminary data on perinatal outcomes of the first 67 newborns are encouraging. PMID:23100477

  5. Polyradiculopathy and Gastroparesis due to Cytomegalovirus Infection in AIDS: A Case Report and Review of Literature

    PubMed Central

    Thongpooswan, Supat; Chyn, Eric; Alfishawy, Mostafa; Restrepo, Erfidia; Berman, Charles; Ahmed, Kawser; Muralidharan, Sethu

    2015-01-01

    Patient: Female, 46 Final Diagnosis: CMV gastroparesis and radiculopathy Symptoms: Nausea • paraplegia • urinary retention • vomiting Medication: — Clinical Procedure: Lumbar puncture Specialty: Infectious Diseases Objective: Unusual clinical course Background: Cytomegalovirus (CMV) infection has been well described as an opportunistic infection of patients with human immunodeficiency virus (HIV). To the best of our knowledge, this is the first case report of a patient with AIDS and lumbosacral polyradiculopathy, associated with gastroparesis resulting from CMV infection. Case Report: A 46-year-old Hispanic woman with a history of HIV for 10 years was admitted to our hospital for nausea, vomiting, urinary retention, and generalized weakness. Bilateral lower extremity examination revealed flaccid paraplegia, decreased sensations from the groin downwards, bilateral lower extremity areflexia, and absent plantar reflexes, with enlarged urinary bladder. CMV was detected in CSF by PCR, and cervical and lumbar magnetic resonance imaging (MRI) revealed intense nodular leptomeningeal enhancement from the lower thoracic cord and extending along the conus medullaris/filum terminalis and nerve roots. Gastric emptying scintigraphy revealed severe delayed gastric emptying time. Ganciclovir was initiated and her neurological symptoms and gastrological symptoms gradually improved. Over 8 weeks, nausea and vomiting resolved and the patient was able to walk before being discharged from the hospital. Conclusions: Polyradiculopathy and gastroparesis can result from CMV infection in AIDS patients. Whether the mechanism is secondary to viral infection or immune systems remains unclear. It is important for physicians to be aware of this uncommon presentation in the antiretroviral therapy (ART) era. CMV treatment should be initiated immediately once diagnosis is confirmed. PMID:26552851

  6. Identification of Symptomatic Fetuses Infected with Cytomegalovirus Using Amniotic Fluid Peptide Biomarkers

    PubMed Central

    Leruez-Ville, Marianne; Ramirez-Torres, Adela; Lacroix, Chrystelle; Breuil, Benjamin; Froment, Carine; Bascands, Jean-Loup; Schanstra, Joost P.; Ville, Yves

    2016-01-01

    Cytomegalovirus (CMV) is the most common cause of congenital infection, and is a major cause of sensorineural hearing loss and neurological disabilities. Evaluating the risk for a CMV infected fetus to develop severe clinical symptoms after birth is crucial to provide appropriate guidance to pregnant women who might have to consider termination of pregnancy or experimental prenatal medical therapies. However, establishing the prognosis before birth remains a challenge. This evaluation is currently based upon fetal imaging and fetal biological parameters, but the positive and negative predictive values of these parameters are not optimal, leaving room for the development of new prognostic factors. Here, we compared the amniotic fluid peptidome between asymptomatic fetuses who were born as asymptomatic neonates and symptomatic fetuses who were either terminated in view of severe cerebral lesions or born as severely symptomatic neonates. This comparison allowed us to identify a 34-peptide classifier in a discovery cohort of 13 symptomatic and 13 asymptomatic neonates. This classifier further yielded 89% sensitivity, 75% specificity and an area under the curve of 0.90 to segregate 9 severely symptomatic from 12 asymptomatic neonates in a validation cohort, showing an overall better performance than that of classical fetal laboratory parameters. Pathway analysis of the 34 peptides underlined the role of viral entry in fetuses with severe brain disease as well as the potential importance of both beta-2-microglobulin and adiponectin to protect the injured fetal brain infected with CMV. The results also suggested the mechanistic implication of the T calcium channel alpha-1G (CACNA1G) protein in the development of seizures in severely CMV infected children. These results open a new field for potential therapeutic options. In conclusion, this study demonstrates that amniotic fluid peptidome analysis can effectively predict the severity of congenital CMV infection. This

  7. Genital Cytomegalovirus Replication Predicts Syphilis Acquisition among HIV-1 Infected Men Who Have Sex with Men

    PubMed Central

    Gianella, Sara; Smith, Davey M.; Daar, Eric S.; Dube, Michael P.; Lisco, Andrea; Vanpouille, Christophe; Margolis, Leonid; Haubrich, Richard H.; Morris, Sheldon R.

    2015-01-01

    Objective Sexually transmitted infections (STI) are common among HIV-infected men who have sex with men (MSM). While behavioral factors are important in STI acquisition, other biological factors such as immune modulation due to chronic viral infection may further predispose to STI acquisition. Design Post Hoc analysis including data collected over 12 months of follow-up from 131 HIV-infected MSM receiving antiretroviral therapy and screened for incident bacterial STI every 3 months. Methods Genital secretions collected at baseline were used to measure herpesvirus replication and inflammatory cytokines. Baseline predictors of STI were determined using survival analysis of time to incident STI. Results All participants were seropositive for cytomegalovirus (CMV), and 52% had detectable genital CMV at baseline. Thirty-five individuals acquired STI during follow-up, sometimes with multiple pathogen (17 syphilis, 21 gonorrhea, 14 chlamydia). Syphilis acquisition was associated with genital CMV replication at baseline (19.1% CMV-shedders versus 4.8% non-shedders, p=0.03) and younger age (p=0.02). Lower seminal MCP-1 was associated with higher seminal CMV levels and with syphilis acquisition (p<0.01). For syphilis acquisition, in multivariable Cox-Proportional Hazard model adjusted hazard rates were 3.56 (95%CI:1.00–12.73) for baseline CMV replication and 2.50 (0.92–6.77) for younger age. Conclusions This post hoc analysis suggest that CMV-associated decrease in seminal MCP-1 levels might predispose HIV-infected MSM to syphilis acquisition, but not other STI. Future studies should determine underlying mechanisms and if a causal association exists. PMID:26061824

  8. Cytomegalovirus Infection following Kidney Transplantation: a Multicenter Study of 3065 Cases

    PubMed Central

    Einollahi, B.

    2012-01-01

    Background: Cytomegalovirus (CMV) infection is a common complication following kidney transplantation. Objective: To assess the incidence and risk factors of CMV infection among renal transplant recipients. Methods: In a retrospective multicenter study, 3065 renal transplant recipients from 17 transplant centers of Iran were studied between April 2008 and January 2011. Kidney transplant patients were routinely monitored by sequential blood samples drawn for use in the CMV-pp65 antigenemia assay, and for hematological and biochemistry tests. Results: 63% of studied patients were males; the mean±SD age of participants was 38±15 years. The majority of cases (81%) received a kidney from a living unrelated donor (LURD), 9% from living related donor (LRD), and 10% from deceased donors. 671 patients experienced CMV viremia. The incidence of CMV infection was 21.9% (95% CI: 20.4%–23.4%). The rate was higher in the first 6 months after transplantation (p<0.001); in recipients with higher level of cyclosporine (p<0.001); in those with lower hemoglobin concentration (p=0.02); patients with elevated ALT (p<0.001); those with increased fasting blood sugar (p=0.005); recipients with dyslipidemia (p<0.05); deceased kidney recipients (p=0.006); and patients with kidney graft impairment (p=0.01). In multivariate regression analysis, time since kidney transplantation (p<0.001) and renal allograft failure (p<0.001) were the only risk factors associated with CMV infection. Conclusions: CMV infection was a common complication in the first 6 months of kidney transplantation, particularly among patients with kidney graft impairment. PMID:25013626

  9. Broncholaveolar lavage to detect cytomegalovirus infection, latency, and reactivation in immune competent hosts.

    PubMed

    Mansfield, Sara; Dwivedi, Varun; Byrd, Sara; Trgovcich, Joanne; Griessl, Marion; Gutknecht, Michael; Cook, Charles H

    2016-08-01

    Roughly 1/3rd of immune competent patients will reactivate latent cytomegalovirus (CMV) during critical illness. There are no standard methods to detect reactivation, and some investigators have postulated that presence of DNA in BAL fluid is indicative of viral replication. To test this hypothesis, we used a murine model that allows inclusion of matched healthy controls which is not possible in human studies. BALB/c mice infected with Smith-murine CMV or PBS (mock) had BAL evaluated 7, 14, or 21 days after acute infections, during latency, or during bacterial sepsis. Plaque assay, PCR, and rtPCR were performed on BALs and concomitantly obtained lung tissue. BAL cellular compositions, including tetramer evaluation of CMV-specific T cells were evaluated by flow cytometry. CMV DNA were detected in BAL at all time-points during acute infection, becoming undetectable in all mice during latency, then were detected again during bacterial sepsis, peaking 3 weeks after onset. mCMV specific T-cells were most numerous in BAL after acute viral infections, decreasing to low levels during latency, then fluctuating during bacterial sepsis. Specifically, mCMV-specific T-cells contracted at sepsis onset, expanding 2-4 weeks post-sepsis, presumably in response to increased viral loads at that time point. Altogether, our results support the use of BAL PCR for the diagnosis of CMV replication in immune competent hosts. Additionally, we demonstrate dynamic changes in CMV-specific T cells that occur in BAL during CMV infection and during sepsis induced viral reactivation. J. Med. Virol. 88:1408-1416, 2016. © 2016 Wiley Periodicals, Inc. PMID:26762116

  10. Assessing the economic merits of managing cytomegalovirus infection in organ and stem cell transplantation.

    PubMed

    Wait, Suzanne; Musingarimi, Primrose; Briggs, Andrew; Tillotson, Glenn

    2009-03-01

    Two preventative approaches exist to manage cytomegalovirus (CMV), a common infection in recipients of organ and stem cell transplants: prophylaxis--the prevention of viraemia--and pre-emptive therapy--the prevention of manifestation of disease in patients who have viraemia. Economic evaluation may provide a helpful framework to inform the choice between these two approaches. However, several issues arise. Direct comparisons of prophylaxis and pre-emptive therapy are rare and there are few epidemiological data that depict the full natural history of CMV infection and disease. There is a need for large, prospective randomised trials that directly compare these two strategies and are of sufficient duration to assess their overall impact on direct and indirect effects of CMV as well as patient quality of life. These methodological issues are relevant to the economic evaluation of preventative measures in other clinical settings and highlight the need for a rigorous evaluative framework to best inform decision making about the optimal strategy for patients. PMID:19450067

  11. Human Cytomegalovirus Infection is Associated with Essential Hypertension in Kazakh and Han Chinese Populations

    PubMed Central

    Tang, Na; Li, Jia-wei; Liu, Yong-min; Zhong, Hua; Wang, La-mei; Deng, Feng-mei; Qu, Yuan-yuan; Hui, Jing; Cheng, Jiang; Tang, Bin; Huang, Gang; Guo, Shu-xia; Li, Xin-zhi; Wei, Li-li; He, Fang

    2014-01-01

    Background We aimed to study the association between cytomegalovirus (CMV) infection and hypertension in Kazakh and Han populations from Xinjiang Province, China. Material/Methods We analyzed data on 800 Kazakhs (467 hypertension patients and 333 healthy control participants) and 800 Hans (482 hypertension patients and 318 healthy control participants) aged 18–84 years old. ELISA and real-time quantitative PCR coupled with restriction fragment length polymorphism analysis were applied for determining CMV infection and glycoprotein B (gB) genotypes, respectively. Results Serologic evidence of CMV infection was obtained for 95.4% and 90.1% of the Kazakhs and Hans, respectively. The CMV seroprevalence rates among the Kazakh and Han participants with hypertension were 96.8% and 89.8%, respectively. Multiple logistic regression analyses revealed statistically significant independent associations between CMV seropositivity and hypertension in Kazakh males and between CMV antibody titers and hypertension in Hans; significant relationships also existed between CMV antibody titers and blood pressure in Hans. In Kazakhs, 3 CMV gB genotypes were identified: gB2 and genotype mixtures gB1+gB2 and gB2+gB3. In Hans, 4 CMV gB genotypes were identified: gB1, gB2, gB1+gB2, and gB2+gB3. Of the 4 studied genotypes, gB2+gB3 showed a significant independent association with hypertension in Kazakh females. Conclusions CMV infection is associated with essential hypertension in Kazakh males and Hans in Xinjiang. CMV seropositivity is associated with hypertension in Kazakh males, and CMV antibody titers are associated with blood pressure and hypertension in Han males and females. Moreover, the CMV gB2+gB3 genotype mixture is associated independently with essential hypertension in Kazakh females. PMID:25448630

  12. Seroprevalence and Risk Factors for Cytomegalovirus (CMV) Infections in Adolescent Males

    PubMed Central

    Stadler, Laura Patricia; Bernstein, David I; Callahan, S. Todd; Ferreira, Jennifer; Gorgone Simone, Gina A.; Edwards, Kathryn M.; Stanberry, Lawrence R.; Rosenthal, Susan L.

    2010-01-01

    Background Congenital cytomegalovirus (CMV) is a leading cause of disability, including sensorineural hearing loss, developmental delay, and mental retardation. Although the seroprevalence of CMV and associated exposure and behavioral risk factors have been reported in adolescent females, limited data exists in males. Method Serum was obtained from males (aged 12–17 years) from 6/2006 – 7/2007 in Cincinnati, OH, Galveston, TX, and Nashville, TN and tested for CMV IgG antibody using a commercial assay. Participants completed a computer assisted screening interview to assess seven risk categories. Results A total of 397 adolescent males were screened and 165 (47%) were seropositive. African American race, older age, and exposure to children ≤3 years of age in the home were significant predictors of CMV infection in the univariate analysis. Hispanic ethnicity, group living situations, saliva sharing behaviors, and intimate sexual contact were not associated with CMV infection. However, among those with a history of sexual contact, the number of life time partners was associated with CMV. In the final multivariate model, CMV seroprevalence was significantly higher in African American subjects (OR 1.99 (95% CI [1.27, 2.95]) and subjects >14 years of age (OR 1.1 (95%CI [1.00, 1.28]. With each additional risk factor, males had a 1.6x increased risk of CMV. Conclusions This study indicates that CMV infections are common in adolescent males, increase with age, and are associated with African American race. Further study is needed to understand these risk factors in preparation for a CMV vaccine targeted at both adolescent males and females. Summary This study indicates CMV infections are common in adolescent males, increase with age, and are associated with African Americans. Further study is needed to understand these risk factors in preparation for a CMV vaccine targeted at adolescent males and females. PMID:20936976

  13. Vaccine-Derived Neutralizing Antibodies to the Human Cytomegalovirus gH/gL Pentamer Potently Block Primary Cytotrophoblast Infection

    PubMed Central

    Chiuppesi, Flavia; Wussow, Felix; Johnson, Erica; Bian, Chao; Zhuo, Meng; Rajakumar, Augustine; Barry, Peter A.; Britt, William J.; Chakraborty, Rana

    2015-01-01

    ABSTRACT Human cytomegalovirus (HCMV) elicits neutralizing antibodies (NAb) of various potencies and cell type specificities to prevent HCMV entry into fibroblasts (FB) and epithelial/endothelial cells (EpC/EnC). NAb targeting the major essential envelope glycoprotein complexes gB and gH/gL inhibit both FB and EpC/EnC entry. In contrast to FB infection, HCMV entry into EpC/EnC is additionally blocked by extremely potent NAb to conformational epitopes of the gH/gL/UL128/130/131A pentamer complex (PC). We recently developed a vaccine concept based on coexpression of all five PC subunits by a single modified vaccinia virus Ankara (MVA) vector, termed MVA-PC. Vaccination of mice and rhesus macaques with MVA-PC resulted in a high titer and sustained NAb that blocked EpC/EnC infection and lower-titer NAb that inhibited FB entry. However, antibody function responsible for the neutralizing activity induced by the MVA-PC vaccine is uncharacterized. Here, we demonstrate that MVA-PC elicits NAb with cell type-specific neutralization potency and antigen recognition pattern similar to human NAb targeting conformational and linear epitopes of the UL128/130/131A subunits or gH. In addition, we show that the vaccine-derived PC-specific NAb are significantly more potent than the anti-gH NAb to prevent HCMV spread in EpC and infection of human placental cytotrophoblasts, cell types thought to be of critical importance for HCMV transmission to the fetus. These findings further validate MVA-PC as a clinical vaccine candidate to elicit NAb that resembles those induced during HCMV infection and provide valuable insights into the potency of PC-specific NAb to interfere with HCMV cell-associated spread and infection of key placental cells. IMPORTANCE As a consequence of the leading role of human cytomegalovirus (HCMV) in causing permanent birth defects, developing a vaccine against HCMV has been assigned a major public health priority. We have recently introduced a vaccine strategy based

  14. Human Cytomegalovirus Inhibits the PARsylation Activity of Tankyrase—A Potential Strategy for Suppression of the Wnt Pathway

    PubMed Central

    Roy, Sujayita; Liu, Fengjie; Arav-Boger, Ravit

    2015-01-01

    Human cytomegalovirus (HCMV) was reported to downregulate the Wnt/β-catenin pathway. Induction of Axin1, the negative regulator of the Wnt pathway, has been reported as an important mechanism for inhibition of β-catenin. Since Tankyrase (TNKS) negatively regulates Axin1, we investigated the effect of HCMV on TNKS expression and poly-ADP ribose polymerase (PARsylation) activity, during virus replication. Starting at 24 h post infection, HCMV stabilized the expression of TNKS and reduced its PARsylation activity, resulting in accumulation of Axin1 and reduction in its PARsylation as well. General PARsylation was not changed in HCMV-infected cells, suggesting specific inhibition of TNKS PARsylation. Similarly, treatment with XAV939, a chemical inhibitor of TNKS’ activity, resulted in the accumulation of TNKS in both non-infected and HCMV-infected cell lines. Reduction of TNKS activity or knockdown of TNKS was beneficial for HCMV, evidenced by its improved growth in fibroblasts. Our results suggest that HCMV modulates the activity of TNKS to induce Axin1, resulting in inhibition of the β-catenin pathway. Since HCMV replication is facilitated by TNKS knockdown or inhibition of its activity, TNKS may serve as an important virus target for control of a variety of cellular processes. PMID:26729153

  15. Successful low-dose leflunomide treatment for ganciclovir-resistant cytomegalovirus infection with high-level antigenemia in a kidney transplant: A case report and literature review.

    PubMed

    Morita, Shinya; Shinoda, Kazunobu; Tamaki, Satoshi; Kono, Hidaka; Asanuma, Hiroshi; Nakagawa, Ken; Oya, Mototsugu

    2016-09-01

    Ganciclovir-resistant cytomegalovirus infection is sometimes life-threatening for organ transplant recipients. Foscarnet is an alternative, although it may potentially worsen the preexistent impaired renal function. Here we report the case of a successful low-dose leflunomide treatment in a kidney transplant recipient with very high viral replication, who underwent kidney transplantation 10 years before. Administering 10mg leflunomide daily for 5 months without a loading dose completely cleared the ganciclovir-resistant cytomegalovirus strains. PMID:27494108

  16. Inhibition of p53 transcriptional activity by human cytomegalovirus UL44.

    PubMed

    Kwon, Yejin; Kim, Mi-Na; Young Choi, Eun; Heon Kim, Jung; Hwang, Eung-Soo; Cha, Chang-Yong

    2012-05-01

    Human cytomegalovirus (HCMV) stimulates cellular synthesis of DNA and proteins and induces transition of the cell cycle from G(1) to S and G(2) /M phase, in spite of increased amounts of p53 in the infected cells. The immediate early protein IE2-86  kDa (IE86) tethers a transcriptional repression domain to p53; however, its repression of p53 function is not enough to abrogate the G(1) checkpoint function of p53. Other HCMV proteins that suppress the activity of p53 were investigated in this study. Of the HCMV proteins that bind to p53 when assessed by immunoprecipitation and immunoblot analysis, HCMV UL44 was chosen as a candidate protein. It was found that reporter gene containing p53 consensus sequence was activated by transfection with wild type p53, but when plasmids of p53 with IE86 or UL44 were co-transfected, p53 transcriptional activity was decreased to 3-7% of the p53 control in a dose-dependent manner. When the deletion mutant of UL44 was co-transected with p53, the carboxyl one-third portion of UL44 had little effect on inhibition of p53 transcriptional activity. The amount of mRNA p21 was measured in H1299 by real time PCR after transfection of the combination of p53 and UL44 vectors and it was found that p21 transcription by p53 was inhibited dose-dependently by UL44. Increased G0/G1 and decreased S phases in p53 wild type-transfected H1299 cells were recovered to the level of p53 mutant type-transfected ones by the additional transfection of UL44 in a dose-dependent manner. In conclusion, the transcriptional activity of p53 is suppressed by UL44 as well as by IE86. PMID:22376288

  17. Subacute autonomic and sensory neuropathy closely related to cytomegalovirus infection preceded by frequent syncopal attacks.

    PubMed

    Nakao, Koichi; Namekawa, Michito; Kondo, Soichi; Ono, Sayaka; Nakano, Imaharu

    2016-08-31

    A 73-year-old woman who had hypertension developed a slight fever and general malaise with laboratory-proven hepatic dysfunction as well as frequent syncopal attacks 3 months before admission to our hospital. One month later, she developed urinary retention and distal limb numbness. Upon admission, her neurological examination showed reduced limb tendon reflexes, glove and stocking-type numbness, and diminished senses of touch, temperature, pain, and distal leg vibration and position. Serum cytomegalovirus (CMV) IgM antibody and CMV IgG antibody were elevated on admission, and both decreased thereafter, confirming CMV infection. No serum anti-ganglioside antibody was detected. Cerebrospinal fluid revealed a mild pleocytosis and elevated proteins. Compound muscle action potential (CMAP) amplitudes of the tibial and peroneal nerve were slightly reduced. Sensory nerve action potential (SNAP) amplitudes of the median and ulnar nerves were reduced, and sural SNAP was not evoked. Systolic blood pressure dropped 48 mmHg when the patient assumed a standing position from a supine one, demonstrating orthostatic hypotension, and a cold pressor test was abnormal, both indicating an obvious hypofunction of the sympathetic nerve. The postganglionic autonomic nerve appeared to be damaged because the accumulation of [(123)I] meta-iodobenzylguanidine was reduced on myocardial scintigraphy. These findings combined together led us to make a diagnosis of subacute autonomic and sensory neuropathy associated with CMV infection in this case. Following an eventless administration of oral fludrocortisones, intravenous immuno-globulin (IVIg) was given after one month of the hospitalization with a remarkable reduction of the syncope. This case is instructive in two points. One is that there may be a couple of months with syncope alone before the sensory disturbance appearance, and the other is that IVIg may be considerably effective for the patient-annoying syncopes. To our knowledge, this

  18. Cytomegalovirus infection in autologous stem cell transplant recipients in the era of rituximab.

    PubMed

    Jain, Tania; John, Jisha; Kotecha, Aditya; Deol, Abhinav; Saliminia, Tanaz; Revankar, Sanjay; Chandrasekar, Pranatharthi

    2016-08-01

    The incidence of cytomegalovirus (CMV) reactivation/disease after autologous stem cell transplant (ASCT) is much lower than that after allogeneic stem cell transplantation. With the recent use of rituximab during cancer chemotherapy or conditioning regimens prior to transplantation, there has been an increasing concern of opportunistic infections including CMV. In the present study, we reviewed the patients undergoing ASCT from December 2007 to December 2013 to identify those developing CMV reactivation/disease. Out of the 978 patients who underwent ASCT at the Karmanos Cancer Institute, 239 patients were tested for symptomatic CMV reactivation based on clinical suspicion. Of the tested patients, 7/239 (2.9 %) were documented to have CMV reactivation within 90 days of ASCT. The median time to develop CMV viremia was 32 days from transplantation. Of the 239 patients tested, CMV viremia was detected in 3 out of 72 patients who received rituximab as compared to 4 out of 167 patients who did not. Three of these seven viremic patients were treated with anti-viral drugs; viremia resolved in all patients at a median of 24 days. Three patients were found to develop other bacterial and/or fungal infections following CMV viremia. Two of the seven patients died during 1-year follow-up, due to primary disease progression or Candida sepsis. None of the patients developed proven tissue-invasive CMV disease. The study did not evaluate the incidence of asymptomatic CMV infection/reactivation. Despite prior publications based on limited data, rituximab does not appear to contribute to an increased frequency of symptomatic CMV reactivation following ASCT. PMID:27225264

  19. Hearing Loss and Cytomegalovirus.

    ERIC Educational Resources Information Center

    Strauss, Melvin

    1997-01-01

    Cytomegalovirus is the most common cause of congenital virally induced hearing loss. Maternal infection is most often asymptomatic as is the infection in the newborn. Hearing loss occurs in both clinically apparent infection and in the asymptomatic infection. Current methods of detection, treatment, and prevention and research efforts are…

  20. Murine cytomegalovirus perturbs endosomal trafficking of major histocompatibility complex class I molecules in the early phase of infection.

    PubMed

    Tomas, Maja Ilić; Kucić, Natalia; Mahmutefendić, Hana; Blagojević, Gordana; Lucin, Pero

    2010-11-01

    Murine cytomegalovirus (MCMV) functions interfere with protein trafficking in the secretory pathway. In this report we used Δm138-MCMV, a recombinant virus with a deleted viral Fc receptor, to demonstrate that MCMV also perturbs endosomal trafficking in the early phase of infection. This perturbation had a striking impact on cell surface-resident major histocompatibility complex class I (MHC-I) molecules due to the complementary effect of MCMV immunoevasins, which block their egress from the secretory pathway. In infected cells, constitutively endocytosed cell surface-resident MHC-I molecules were arrested and retained in early endosomal antigen 1 (EEA1)-positive and lysobisphosphatidic acid (LBPA)-negative perinuclear endosomes together with clathrin-dependent cargo (transferrin receptor, Lamp1, and epidermal growth factor receptor). Their progression from these endosomes into recycling and degradative routes was inhibited. This arrest was associated with a reduction of the intracellular content of Rab7 and Rab11, small GTPases that are essential for the maturation of recycling and endolysosomal domains of early endosomes. The reduced recycling of MHC-I in Δm138-MCMV-infected cells was accompanied by their accelerated loss from the cell surface. The MCMV function that affects cell surface-resident MHC-I was activated in later stages of the early phase of viral replication, after the expression of known immunoevasins. MCMV without the three immunoevasins (the m04, m06, and m152 proteins) encoded a function that affects endosomal trafficking. This function, however, was not sufficient to reduce the cell surface expression of MHC-I in the absence of the transport block in the secretory pathway. PMID:20719942

  1. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines.

    PubMed

    Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

    2016-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy. PMID:26740871

  2. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines

    PubMed Central

    Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

    2016-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy. PMID:26740871

  3. Murine Cytomegalovirus Capsid Assembly Is Dependent on US22 Family Gene M140 in Infected Macrophages▿

    PubMed Central

    Hanson, Laura K.; Slater, Jacquelyn S.; Cavanaugh, Victoria J.; Newcomb, William W.; Bolin, Lisa L.; Nelson, Christine N.; Fetters, Lisa D.; Tang, Qiyi; Brown, Jay C.; Maul, Gerd G.; Campbell, Ann E.

    2009-01-01

    Macrophages are an important target cell for infection with cytomegalovirus (CMV). A number of viral genes that either are expressed specifically in this cell type or function to optimize CMV replication in this host cell have now been identified. Among these is the murine CMV (MCMV) US22 gene family member M140, a nonessential early gene whose deletion (RVΔ140) leads to significant impairment in virus replication in differentiated macrophages. We have now determined that the defect in replication is at the stage of viral DNA encapsidation. Although the rate of RVΔ140 genome replication and extent of DNA cleavage were comparable to those for revertant virus, deletion of M140 resulted in a significant reduction in the number of viral capsids in the nucleus, and the viral DNA remained sensitive to DNase treatment. These data are indicative of incomplete virion assembly. Steady-state levels of both the major capsid protein (M86) and tegument protein M25 were reduced in the absence of the M140 protein (pM140). This effect may be related to the localization of pM140 to an aggresome-like, microtubule organizing center-associated structure that is known to target misfolded and overexpressed proteins for degradation. It appears, therefore, that pM140 indirectly influences MCMV capsid formation in differentiated macrophages by regulating the stability of viral structural proteins. PMID:19458005

  4. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    SciTech Connect

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-12-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.

  5. Identification and Analysis of the Porcine MicroRNA in Porcine Cytomegalovirus-Infected Macrophages Using Deep Sequencing

    PubMed Central

    Liu, Xiao; Liao, Shan; Xu, Zhiwen; Zhu, Ling; Yang, Fan; Guo, Wanzhu

    2016-01-01

    Porcine cytomegalovirus (PCMV; genus Cytomegalovirus, subfamily Betaherpesvirinae, family Herpesviridae) is an immunosuppressive virus that mainly inhibits the immune function of T lymphocytes and macrophages, which has caused substantial damage in the farming industry. In this study, we obtained the miRNA expression profiles of PCMV-infected porcine macrophages via high-throughput sequencing. The comprehensive analysis of miRNA profiles showed that 239 miRNA database-annotated and 355 novel pig-encoded miRNAs were detected. Of these, 130 miRNAs showed significant differential expression between the PCMV-infected and uninfected porcine macrophages. The 10 differentially expressed pig-encoded miRNAs were further determined by stem-loop reverse-transcription polymerase chain reaction, and the results were consistent with the high-throughput sequencing. Gene Ontology analysis of the target genes of miRNAs in PCMV-infected porcine macrophages showed that the differentially expressed miRNAs are mainly involved in immune and metabolic processes. This is the first report of the miRNA transcriptome in porcine macrophages and an analysis of the miRNA regulatory mechanisms during PCMV infection. Further research into the regulatory mechanisms of miRNAs during immunosuppressive viral infections should contribute to the treatment and prevention of immunosuppressive viruses. PMID:26943793

  6. [A steroid-responsive case of severe rhabdomyolysis associated with cytomegalovirus infection].

    PubMed

    Sato, Keishiro; Yoneda, Makoto; Hayashi, Koji; Nakagawa, Hiroto; Higuchi, Itsuro; Kuriyama, Masaru

    2006-05-01

    A 31-year-old man was admitted to our hospital, complaining of muscular weakness and pain in the legs one month after a common cold. On admission, neurological examinations demonstrated moderate weakness in the arms and mild weakness in the legs with decreased or diminished deep tendon reflexes, and mild dysphagia. Weakness was gradually extended to the arm, throat and respiratory muscles, requiring artificial ventilation. Laboratory examinations demonstrated increased levels of CK (upto 24,380 IU/L) and positive anti-cytomegalovirus (CMV) -IgM antibodies in the serum, and myogloburinuria. CMV was not detected in either the blood cells or muscles by PCR. There were no antibodies against viruses including Ebstein-Barr virus and HIV, in the serum. There were no autoantibodies related to collagen diseases in the serum. Systemic PET scan did not show any evidence of malignancy. Bone marrow biopsy did not show any atypical cells. Muscle MRI demonstrated mild atrophy with high intensity signals in part. Muscle biopsy demonstrated scattered necrotic and regenerated muscle fibers without inflammatory cell infiltration. The patient was therefore diagnosed as having rhabdomyolysis associated with CMV infection. After three courses of intravenously administered high dose methylprednislone over three days, muscle weakness improved gradually, and the serum CK level was normalized in two months. The patient recovered and was removed from artificial ventilation three months after the therapy. There were no sign of renal failure. Steroid therapy should be considered for the treatment of rhabdomyolysis or myopathy associated with CMV infection in order to prevent renal failure or fatal progression of the disease. PMID:16886796

  7. Incidence and dynamics of active cytomegalovirus infection in allogeneic stem cell transplant patients according to single nucleotide polymorphisms in donor and recipient CCR5, MCP-1, IL-10, and TLR9 genes.

    PubMed

    Corrales, Isabel; Giménez, Estela; Solano, Carlos; Amat, Paula; de la Cámara, Rafael; Nieto, José; Garcia-Noblejas, Ana; Navarro, David

    2015-02-01

    Single nucleotide polymorphisms (SNPs) in genes involved in the activation or regulation of innate and adaptive immune responses may modulate the susceptibility to and the natural history of certain chronic viral infections. The current study aimed to investigate whether donor and recipient SNPs in the chemokine receptor 5 (rs1800023), monocyte chemoattractant protein 1 (rs13900), interleukin-10 (rs1878672), and Toll-like receptor 9 (rs352140) genes would exert any influence on the rate of incidence and features of CMV DNAemia in the allogeneic stem cell transplantation setting. This was a retrospective observational multicenter study. The cohort consisted of 102 non-consecutive allogeneic stem cell transplant recipients. SNP genotyping was performed by allele-specific real-time PCR. CMV surveillance was performed by the pp65 antigenemia assay/and or by real-time PCR. Seventy-three patients developed CMV DNAemia within the first 100 days after transplantation (71.5%). Neither donor nor recipient SNPs were associated significantly with the rate of incidence of active CMV infection, nor with the need for pre-emptive antiviral therapy. Both the duration of CMV DNAemia and the plasma CMV DNA peak load during episodes were significantly higher in patients harboring the donor (but not the recipient) chemokine receptor 5 A/A genotype, than in their A/G and G/G counterparts (P = 0.022 and P = 0.045, respectively). The data reported suggest that SNPs in chemokine receptor 5 may influence the dynamics of CMV infection in the Allo-SCT setting. PMID:25132583

  8. An inducible promoter mediates abundant expression from the immediate-early 2 gene region of human cytomegalovirus at late times after infection.

    PubMed Central

    Puchtler, E; Stamminger, T

    1991-01-01

    An abundant late transcript of 1.5 kb originates from the immediate-early 2 (IE-2) gene region of human cytomegalovirus (HCMV) at late times after infection. The transcriptional start of this RNA was precisely mapped, and the putative promoter region was cloned in front of the CAT gene as reporter. This region, which comprises 78 nucleotides of IE-2 sequence upstream of the determined cap site, was strongly activated by viral superinfection at late times in the replicative cycle. As shown by RNase protection analyses, the authentic transcription start is used. No activation of this late promoter was observed after cotransfection with an expression plasmid containing the HCMV IE-1 and -2 gene region. This result suggests that, compared with early and early late promoters of HCMV, different or additional viral functions are required for the activation of true late promoters. Images PMID:1656096

  9. Mast cells expedite control of pulmonary murine cytomegalovirus infection by enhancing the recruitment of protective CD8 T cells to the lungs.

    PubMed

    Ebert, Stefan; Becker, Marc; Lemmermann, Niels A W; Büttner, Julia K; Michel, Anastasija; Taube, Christian; Podlech, Jürgen; Böhm, Verena; Freitag, Kirsten; Thomas, Doris; Holtappels, Rafaela; Reddehase, Matthias J; Stassen, Michael

    2014-04-01

    The lungs are a noted predilection site of acute, latent, and reactivated cytomegalovirus (CMV) infections. Interstitial pneumonia is the most dreaded manifestation of CMV disease in the immunocompromised host, whereas in the immunocompetent host lung-infiltrating CD8 T cells confine the infection in nodular inflammatory foci and prevent viral pathology. By using murine CMV infection as a model, we provide evidence for a critical role of mast cells (MC) in the recruitment of protective CD8 T cells to the lungs. Systemic infection triggered degranulation selectively in infected MC. The viral activation of MC was associated with a wave of CC chemokine ligand 5 (CCL5) in the serum of C57BL/6 mice that was MC-derived as verified by infection of MC-deficient Kit(W-sh/W-sh) "sash" mutants. In these mutants, CD8 T cells were recruited less efficiently to the lungs, correlating with enhanced viral replication and delayed virus clearance. A causative role for MC was verified by MC reconstitution of "sash" mice restoring both, efficient CD8 T-cell recruitment and infection control. These results reveal a novel crosstalk axis between innate and adaptive immune defense against CMV, and identify MC as a hitherto unconsidered player in the immune surveillance at a relevant site of CMV disease. PMID:24763809

  10. Detection of human cytomegalovirus antigenaemia: a rapid diagnostic technique for predicting cytomegalovirus infection/pneumonitis in lung and heart transplant recipients.

    PubMed Central

    Egan, J. J.; Barber, L.; Lomax, J.; Fox, A.; Yonan, N.; Rahman, A. N.; Campbell, C. S.; Deiraniya, A. K.; Carroll, K. B.; Craske, J.

    1995-01-01

    BACKGROUND--New rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromised patients at risk of developing CMV disease. The use of human CMV antigenaemia as a predictor of clinical CMV infection and disease in lung and heart transplant recipients was studied prospectively. METHODS--Twenty three heart and nine lung transplant recipients who survived 40 days were observed by standard CMV surveillance with serological testing, culture, and by sequential testing for CMV antigenaemia. CMV antigenaemia testing is a rapid and quantifiable technique in which a viral lower matrix protein is detected in cytospin preparations of peripheral blood polymorphonuclear leucocytes (PMNLs) by immunofluorescent staining. RESULTS--Eleven patients developed CMV infection and five developed CMV disease (four pneumonitis, one duodenitis). These clinical events occurred at a median of 65 days following transplantation. CMV antigenaemia occurred in 17 patients at a median of 35 days following transplantation. Detection of CMV antigenaemia had a sensitivity of 100%, a specificity of 93.7%, and a positive predictive value of 94.1% for CMV related illness. CMV antigenaemia was positive at a significant interval before the clinical event. High levels of CMV antigenaemia (> 50 CMV antigen positive cells/2 x 10(5) PMNLs) occurred in 11 patients and five of these developed disease. CMV antigenaemia of > 50 CMV antigen positive cells/2 x 10(5) PMNLs had a positive predictive value of 45.5% for disease but a negative predictive value of 100%. Patients with disease had higher levels of antigenaemia than those without disease. CONCLUSIONS--CMV antigenaemia is a rapid diagnostic technique which can identify patients likely to develop CMV disease, potentially allowing early treatment. Images PMID:7886659

  11. Trehalose, an mTOR-Independent Inducer of Autophagy, Inhibits Human Cytomegalovirus Infection in Multiple Cell Types

    PubMed Central

    Belzile, Jean-Philippe; Sabalza, Maite; Craig, Megan; Clark, Elizabeth; Morello, Christopher S.

    2015-01-01

    ABSTRACT Human cytomegalovirus (HCMV) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. Previous studies have shown that the induction of autophagy can inhibit the replication of several different types of DNA and RNA viruses. The goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of HCMV. Most prior studies have used agents that induce autophagy via inhibition of the mTOR pathway. However, since HCMV infection alters the sensitivity of mTOR kinase-containing complexes to inhibitors, we sought an alternative method of inducing autophagy. We chose to use trehalose, a nontoxic naturally occurring disaccharide that is found in plants, insects, microorganisms, and invertebrates but not in mammals and that induces autophagy by an mTOR-independent mechanism. Given the many different cell targets of HCMV, we proceeded to determine whether trehalose would inhibit HCMV infection in human fibroblasts, aortic artery endothelial cells, and neural cells derived from human embryonic stem cells. We found that in all of these cell types, trehalose induces autophagy and inhibits HCMV gene expression and production of cell-free virus. Treatment of HCMV-infected neural cells with trehalose also inhibited production of cell-associated virus and partially blocked the reduction in neurite growth and cytomegaly. These results suggest that activation of autophagy by the natural sugar trehalose or other safe mTOR-independent agents might provide a novel therapeutic approach for treating HCMV disease. IMPORTANCE HCMV infects multiple cell types in vivo, establishes lifelong persistence in the host, and can cause serious health problems for fetuses and immunocompromised individuals. HCMV, like all other persistent pathogens, has to finely tune its interplay with the host cellular machinery to replicate efficiently and evade

  12. Cytomegalovirus retinitis

    MedlinePlus

    ... to prevent its return. Alternative Names Cytomegalovirus retinitis Images Eye CMV retinitis CMV (cytomegalovirus) References Crumpacker CS. ... 5. Read More Antibody HIV/AIDS Immune response Retinal detachment Systemic WBC count Update Date 12/10/ ...

  13. Cytomegalovirus Infection and Atherosclerosis in Candidate of Coronary Artery Bypass Graft

    PubMed Central

    Heybar, Habib; Alavi, Seyed Mohammad; Farashahi Nejad, Mehdi; Latifi, Mahmood

    2015-01-01

    Background: Although there is enough evidence that infectious agents such as Chlamydia pneumonia and Helicobacter pylori may play a pathogenic role in atherosclerosis, this role for cytomegalovirus (CMV) is yet controversial. Objectives: The aim of the present study was to detect CMV-DNA in atherosclerotic plaques in patients who underwent coronary artery bypass graft (CABG). Patients and Methods: In this case-control study, candidates for CABG (cases) and patients with valvular or congenital malformation but without atherosclerotic plaques (controls) were studied from 2012 to 2013 at Golestan hospital, Ahvaz, IR Iran. Demographic and laboratory data were collected. Atherosclerotic and histological samples were obtained from visible plaques and from aorta by the surgeon. All the samples were examined for the presence of CMV-DNA by polymerase chain reaction (PCR) method using a commercial kit (SinaClon, Tehran, IR Iran). Results: The mean ages in case and control groups were 60.8 ± 6.8 and 57.5 ± 11.5 years, respectively, with no significant difference (P = 0.09). Thirty patients (54.5%) in case and 32 (58.2%) in control groups were male with no significant difference (P = 0.7). CMV-DNA was present in 8 (14.5%) of the cases and 2 (4%) of the controls. CMV-DNA was associated with higher risk of atherosclerosis (OR: 7.7, 95% CI = 1.1-51.4, P = 0.03). Of the total normal aortic samples (55 in cases and 55 in controls), there was no individual with simultaneous positive CMV-DNA among aortic atherosclerotic and normal tissue samples. Conclusions: The presence of CMV-DNA in aortic plaques is associated with increased risk of atherosclerosis. CMV infection may be considered as an independent risk factor for this event. PMID:25834719

  14. Cytomegalovirus Infection in Ireland: Seroprevalence, HLA Class I Alleles, and Implications.

    PubMed

    Hassan, Jaythoon; O'Neill, Derek; Honari, Bahman; De Gascun, Cillian; Connell, Jeff; Keogan, Mary; Hickey, David

    2016-02-01

    Cytomegalovirus (CMV) infections occur worldwide and primary infection usually occurs in early childhood and is often asymptomatic whereas primary infection in adults may result in symptomatic illness. CMV establishes a chronic latent infection with intermittent periods of reactivation. Primary infection or reactivation associate with increased mortality and morbidity in those who are immunocompromised. Transplacental transmission may result in significant birth defects or long-term sensorineural hearing loss.We performed a study to determine the CMV seroprevalence and the association between HLA Class I alleles and frequency of CMV infection in Ireland. The presence of CMV IgG, a marker of previous CMV infection, was determined for a cohort of 1849 HLA typed solid organ transplant donors between 1990 and 2013. The presence of CMV IgG was correlated with HLA type.The CMV seroprevalence in solid organ transplant donors was 33.4% (range 22-48% per annum) over the time period 1990 to 2013. Multivariate logistic regression analysis showed that both age and HLA alleles were associated with CMV seropositivity. A significant and positive relationship between age and CMV seropositivity was observed (OR = 1.013, P < 0.001, CI [1.007, 1.019]). Chi-square analysis revealed that the female gender was independently associated with CMV seropositivity (P < 0.01). Seroprevalence in women of reproductive age (20-39 years) was significantly higher than men of the same age (37% vs 26%, P < 0.01). The frequencies of HLA-A1, HLA-A2, and HLA-A3 in our cohort were 40.8%, 48.8%, and 25.9%, respectively. Logistic regression analysis showed that the presence of HLA-A1 but not HLA-A2 or HLA-A3 was independently associated with CMV seronegativity (P < 0.01). Interestingly, individuals who co-expressed HLA-A2 and HLA-A3 alleles were significantly more likely to be CMV seropositive (P < 0.02). The frequencies of HLA-B5, HLA-B7, and HLA-B8 in our cohort were 6.1%, 31

  15. Pneumonia associated with infection with pneumocystis, respiratory syncytial virus, chlamydia, mycoplasma, and cytomegalovirus in children in Papua New Guinea.

    PubMed Central

    Shann, F; Walters, S; Pifer, L L; Graham, D M; Jack, I; Uren, E; Birch, D; Stallman, N D

    1986-01-01

    Paired serum samples were collected from 94 children with pneumonia admitted to Goroka Hospital, Papua New Guinea. All but three of the children were aged 1-24 months. Only nine children were malnourished, with weight for age less than 70% of the Harvard median (three had weight for age less than 60% of the Harvard median). Pneumocystis carinii antigen was detected in the serum of 23 children. Twenty two children had serological evidence of recent infection with respiratory syncytial virus. Five children were probably infected with Chlamydia trachomatis at the time of the study, and there was less convincing serological evidence of current infection in a further 11 children. Five children showed a fourfold rise in antibody to Mycoplasma pneumoniae. Although only one child showed a fourfold rise in antibody to cytomegalovirus, 86 children had this antibody. No child showed a fourfold rise in antibody to Ureaplasma urealyticum or Legionella pneumophila. P carinii, respiratory syncytial virus, C trachomatis, M pneumoniae, and cytomegalovirus may be important causes of pneumonia in children in developing countries. PMID:3002538

  16. The prevalence and risk factors of cytomegalovirus infection in inflammatory bowel disease in Wuhan, Central China

    PubMed Central

    2013-01-01

    Background The etiology of inflammatory bowel disease (IBD) is not clear and cytomegalovirus (CMV) infection is often associated with IBD patients. The etiologic link between IBD and CMV infection needs to be studied. The objective of the present study is to investigate the prevalence and risk factors of CMV in a cohort of IBD patients from Central China. Methods Two hundred and twenty six IBD patients (189 ulcerative colitis (UC) and 37 patients with Crohn’s disease (CD)), and 290 age and sex matched healthy controls were recruited. CMV DNA was detected by nested PCR, while serum anti-CMV IgG and anti-CMV IgM was determined by ELISAs. Colonoscopy/enteroscopy with biopsy of diseased tissues and subsequent H&E stain were then conducted in IBD patients with positive anti-CMV IgM. Finally, we analyzed the prevalence and clinical risk factors of CMV infection in IBD patients. Results The prevalence of CMV DNA and anti-CMV IgG positive rate in IBD patients were 84.07% and 76.11%, respectively, higher than those in healthy controls (59.66% and 50.69%, respectively, P < 0.05), However, anti-CMV IgM positive rate was no different with healthy controls (1.77% vs 0.34%, P = 0.235). In univariate analysis of risk factors, the recent use of corticosteroid was associated with increase of CMV DNA and IgM positive rate in UC (P = 0.035 and P = 0.015, respectively), aminosalicylic acid drug therapy was correlated with positivity of CMV DNA and IgG in UC and CMV DNA in CD (P = 0.041, P < 0.001 and P = 0.014, respectively), the treatment of immunosuppresent was correlated with CMV IgM (P < 0.001). Furthermore, patients with severe UC were significantly associated with CMV DNA and IgM (P = 0.048 and P = 0.031, respectively). Malnutrition (albumin < 35 G/L) was also found to be related with CMV recent infection (P = 0.031). In multivariate analysis of risk factors in UC, pancolitis was significantly associated with CMV DNA positivity

  17. Cytomegalovirus infection in children with Down syndrome in a day-care center in Brazil.

    PubMed

    do Canto, C L; Granato, C F; Garcez, E; Villas Boas, L S; Fink, M C; Estevam, M P; Pannuti, C S

    2000-01-01

    This study evaluates the transmission of CMV infection in 120 children aged 1 to 15 years with Down syndrome who attended a day-care center for handicapped children in São Paulo, Brazil. A blood sample was obtained from each children at the beginning of the study for detection of IgG and IgM cytomegalovirus (CMV) antibodies by an immunofluorescence assay. Samples of saliva and urine were obtained every 3 months from the children with CMV antibodies to detect shedding of the virus by culture in human foreskin fibroblasts, by detection of pp65 CMV-antigen and by a nested PCR assay. The prevalence of anti CMV-IgG antibodies was 76.6% (92/120), and IgM anti-CMV antibodies were detected in 13% (12/92) of the seropositive children. During the first viral evaluation, CMV was detected in the urine and/or saliva in 39/90 (43.3%) of the seropositive children. In the second and third evaluations, CMV was detected in 41/89 (46%) and in 35/89 (39.3%) children, respectively. Detection of CMV was shown both in urine and saliva in 28/39 (71.8%), 19/41(46.3%) and 20/35 (57.1%) of the children excreting the virus, respectively. Additionally, in 3(3/4)9 (67.4%) of the excreters CMV could be demonstrated in urine or saliva in at least two out of the three virological evaluations carried out sequentially in a six month period. Of the 28 initially seronegative children, 26 were re-examined for anti-CMV IgG antibodies about 18 months after the negative sample; seroconversion was found in 10/26 (38.5%). Taking all 536 samples of urine or saliva examined by virus culture and pp65 antigen detection during the study into account, 159 (29.6%) were positive by virus culture and 59 (11%) gave a positive result with the pp65 assay. These data demonstrate the high prevalence of CMV shedding and the high risk of CMV infection in children with Down syndrome attending a day-care center for mentally handicapped patients. The virus culture was more sensitive than the pp65 CMV antigen assay for CMV

  18. Carotid atherosclerosis, cytomegalovirus infection, and cognitive decline in the very old: a community-based prospective cohort study.

    PubMed

    Kawasaki, Midori; Arai, Yasumichi; Takayama, Michiyo; Hirata, Takumi; Takayama, Midori; Abe, Yukiko; Niimura, Hidehito; Mimura, Masaru; Takebayashi, Toru; Hirose, Nobuyoshi

    2016-04-01

    To investigate various risk factors of cognitive decline in the very old, we studied 494 subjects over 85 years old without diagnosis of dementia at baseline from the Tokyo Oldest Old Survey on Total Health, an ongoing, community-based cohort in Japan. Cognitive function was assessed at baseline and at 3-year follow-up using Mini-Mental State Examination (MMSE). Plasma samples were assayed for levels of cytomegalovirus (CMV) immunoglobulin G (IgG) antibodies, tumor necrosis factor-alpha, interleukin-6, and blood chemistry. Carotid artery plaques were measured using an ultrasonography. In the cross-sectional analyses using Tobit regression, individuals with high carotid artery plaque score (≥5.0) had MMSE scores that were 1.08 points lower compared to those with no plaque (95 % confidence interval (CI) -1.95 to -0.20; p = 0.016), adjusted for age, sex, and education. Individuals with CMV IgG titers in the highest quartile had MMSE scores that were 1.47 points lower compared to individuals in the lowest quartile (95 % CI -2.44 to -0.50; p = 0.003). CMV and carotid atherosclerosis showed evidence of an interaction, where the association between CMV and MMSE was present only in subjects with carotid artery plaque. In the longitudinal analyses using linear regression, carotid atherosclerosis, smoking, low grip strength, and poor activities of daily living (ADL) status were associated with faster cognitive decline, adjusted for age, sex, education, and baseline cognitive function. Our findings suggest that carotid atherosclerosis is consistently associated with low cognitive function in the very old and modifies the association between latent CMV infection and cognition. PMID:26886582

  19. A novel flow cytometry-based tool for determining the efficiency of human cytomegalovirus infection in THP-1 derived macrophages.

    PubMed

    Li, Huifen; Mao, Genxiang; Carlson, Joshua; Leng, Sean X

    2015-09-01

    Human cytomegalovirus (hCMV) is a ubiquitous pathogen that causes congenital infection and severe infections in immunocompromised patients. Chronic hCMV infection may also play an important role in immunosenescence and adverse health outcomes in older adults. THP-1, a human monocytic cell line and its derived macrophages serve as a useful cell culture model for mechanistic studies of hCMV infection and its underlying biology. A major methodological challenge is the lack of a quick and reliable tool to accurately determine the efficiency of hCMV infection in THP-1 derived macrophages. In this study, we developed a flow cytometry based method using commercially available monoclonal antibody (MAb) against hCMV immediate early (IE) antigen that can accurately determine infection efficiency. We used 0.5% formaldehyde for fixation, 90% methanol for permeabilization, and incubation with FITC conjugated MAb at 37°C. The method was tested by hCMV infection with laboratory Towne strain in the presence or absence of hydrocortisone. It was also compared with the routine flow cytometry protocol using Cytofix/Cytoperm solution and with immunofluorescence. The results indicate that this new method is reliable and time saving for accurate determination of infection efficiency. It may facilitate further investigations into the underlying biological mechanisms of hCMV infection. PMID:25958130

  20. Cytomegalovirus Infection in Pediatric Hematopoietic Stem Cell Transplantation: Risk Factors for Primary Infection and Cases of Recurrent and Late Infection at a Single Center.

    PubMed

    Rowe, R Grant; Guo, Dongjing; Lee, Michelle; Margossian, Steven; London, Wendy B; Lehmann, Leslie

    2016-07-01

    Cytomegalovirus (CMV) infection is a significant source of morbidity and mortality in allogeneic stem cell transplantation (SCT). We identified a cohort of 91 pediatric SCT patients at risk (defined as either donor and/or recipient seropositivity) for CMV infection at our institution. We retrospectively categorized at-risk SCT recipients as those who (1) were at risk of CMV infection in the post-SCT period, (2) had documented CMV infection before SCT, (3) experienced recurrence of post-SCT CMV viremia, or (4) experienced late post-SCT CMV viremia; categories were not mutually exclusive. We analyzed the impact of SCT-related factors on incidence of CMV infection and outcome, and we described the outcome of each of these cohorts. In univariate analysis, recipient CMV seropositivity, use of umbilical cord blood graft, and acute graft-versus-host disease (GVHD) predicted post-SCT CMV viremia, and the effects of acute GVHD (odds ratio, 4.018; 95% confidence interval, 1.032 to 15.643) and CMV seropositivity (odds ratio, 16.525; 95% confidence interval, 2.041 to 133.803) were confirmed in multivariate analysis. Patients with recurrence of post-SCT CMV viremia had a 50% all-cause mortality rate, compared with 12% in all 91 patients. Patients with pre-SCT CMV infection had a high incidence of post-SCT CMV infection but could successfully undergo SCT with antiviral prophylaxis and pre-emptive CMV treatment. All patients with late CMV infection had prior GVHD. Theses findings identify risk factors for post-SCT CMV infection and provide novel descriptions of childhood SCT recipients with pre-SCT, recurrent, and late CMV infection, which may contribute to risk stratification strategies for CMV at-risk patients in pediatric allogeneic SCT. PMID:27090959

  1. HUMORAL ANTIBODY RESPONSE TO INDIVIDUAL VIRAL PROTEINS AFTER MURINE CYTOMEGALOVIRUS INFECTION

    EPA Science Inventory

    The purpose of this study was to identify viral proteins that played an important role in the humoral immune response to murine cytomegalovirus (MCMV). Viral proteins were separated from a purified virus preparation on polyacrylamide gels, were blotted onto nitrocellulose strips,...

  2. Congenital Cytomegalovirus Infection: A Significant Cause of Deafness and Mental Deficiency.

    ERIC Educational Resources Information Center

    Eichhorn, Sarah K.

    1982-01-01

    Research on cytomegalovirus (CMV), a herpes virus causing neurological damage (hearing problems and/or mental retardation) in 10 percent of infants born with the condition, is reviewed. Incidence of hearing and retardation in CMV cases is reported and current treatment described. (CL)

  3. Human cytomegalovirus induces JC virus DNA replication in human fibroblasts.

    PubMed Central

    Heilbronn, R; Albrecht, I; Stephan, S; Bürkle, A; zur Hausen, H

    1993-01-01

    JC virus, a human papovavirus, is the causative agent of the demyelinating brain disease progressive multifocal leucoencephalopathy (PML). PML is a rare but fatal disease which develops as a complication of severe immunosuppression. Latent JC virus is harbored by many asymptomatic carriers and is transiently reactivated from the latent state upon immunosuppression. JC virus has a very restricted host range, with human glial cells being the only tissue in which it can replicate at reasonable efficiency. Evidence that latent human cytomegalovirus is harbored in the kidney similar to latent JC virus led to the speculation that during episodes of impaired immunocompetence, cytomegalovirus might serve as helper virus for JC virus replication in otherwise nonpermissive cells. We show here that cytomegalovirus infection indeed leads to considerable JC virus DNA replication in cultured human fibroblasts that are nonpermissive for the replication of JC virus alone. Cytomegalovirus-mediated JC virus replication is dependent on the JC virus origin of replication and T antigen. Ganciclovir-induced inhibition of cytomegalovirus replication is associated with a concomitant inhibition of JC virus replication. These results suggest that reactivation of cytomegalovirus during episodes of immunosuppression might lead to activation of latent JC virus, which would enhance the probability of subsequent PML development. Ganciclovir-induced repression of both cytomegalovirus and JC virus replication may form the rational basis for the development of an approach toward treatment or prevention of PML. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8248262

  4. Heterogeneity of CD4+ and CD8+ T-cell responses to cytomegalovirus in HIV-infected and HIV-uninfected men who have sex with men.

    PubMed

    Li, Huifen; Margolick, Joseph B; Bream, Jay H; Nilles, Tricia L; Langan, Susan; Bui, Hanhvy T; Sylwester, Andrew W; Picker, Louis J; Leng, Sean X

    2014-08-01

    Studies of T-cell immunity to human cytomegalovirus (CMV) primarily reflect anti-CMV pp65 or immediate early antigen 1 (IE-1) activity. We assessed responses of T cells from human immunodeficiency virus (HIV)-negative and HIV-infected men to peptide pools spanning 19 CMV open reading frames selected because they previously correlated with total CMV-specific T-cell responses in healthy donors. Cells producing cytokines in response to pp65 or IE-1 together composed <12% and <40% of the total CD4(+) and CD8(+) T-cell responses to CMV, respectively. These proportions were generally similar regardless of HIV serostatus. Thus, analyses of total CMV-specific T-cell responses should extend beyond pp65 and IE-1 regardless of HIV serostatus. PMID:24532602

  5. Glucocorticosteroids trigger reactivation of human cytomegalovirus from latently infected myeloid cells and increase the risk for HCMV infection in D+R+ liver transplant patients

    PubMed Central

    Van Damme, Ellen; Sauviller, Sarah; Lau, Betty; Kesteleyn, Bart; Griffiths, Paul; Burroughs, Andrew; Emery, Vincent; Sinclair, John

    2015-01-01

    Graft rejection in transplant patients is managed clinically by suppressing T-cell function with immunosuppressive drugs such as prednisolone and methylprednisolone. In such immunocompromised hosts, human cytomegalovirus (HCMV) is an important opportunistic pathogen and can cause severe morbidity and mortality. Currently, the effect of glucocorticosteroids (GCSs) on the HCMV life cycle remains unclear. Previous reports showed enhanced lytic replication of HCMV in vitro in the presence of GCSs. In the present study, we explored the implications of steroid exposure on latency and reactivation. We observed a direct effect of several GCSs used in the clinic on the activation of a quiescent viral major immediate-early promoter in stably transfected THP-1 monocytic cells. This activation was prevented by the glucocorticoid receptor (GR) antagonist Ru486 and by shRNA-mediated knockdown of the GR. Consistent with this observation, prednisolone treatment of latently infected primary monocytes resulted in HCMV reactivation. Analysis of the phenotype of these cells showed that treatment with GCSs was correlated with differentiation to an anti-inflammatory macrophage-like cell type. On the basis that these observations may be pertinent to HCMV reactivation in post-transplant settings, we retrospectively evaluated the incidence, viral kinetics and viral load of HCMV in liver transplant patients in the presence or absence of GCS treatment. We observed that combination therapy of baseline prednisolone and augmented methylprednisolone, upon organ rejection, significantly increased the incidence of HCMV infection in the intermediate risk group where donor and recipient are both HCMV seropositive (D+R+) to levels comparable with the high risk D+R− group. PMID:25312585

  6. Glucocorticosteroids trigger reactivation of human cytomegalovirus from latently infected myeloid cells and increase the risk for HCMV infection in D+R+ liver transplant patients.

    PubMed

    Van Damme, Ellen; Sauviller, Sarah; Lau, Betty; Kesteleyn, Bart; Griffiths, Paul; Burroughs, Andrew; Emery, Vincent; Sinclair, John; Van Loock, Marnix

    2015-01-01

    Graft rejection in transplant patients is managed clinically by suppressing T-cell function with immunosuppressive drugs such as prednisolone and methylprednisolone. In such immunocompromised hosts, human cytomegalovirus (HCMV) is an important opportunistic pathogen and can cause severe morbidity and mortality. Currently, the effect of glucocorticosteroids (GCSs) on the HCMV life cycle remains unclear. Previous reports showed enhanced lytic replication of HCMV in vitro in the presence of GCSs. In the present study, we explored the implications of steroid exposure on latency and reactivation. We observed a direct effect of several GCSs used in the clinic on the activation of a quiescent viral major immediate-early promoter in stably transfected THP-1 monocytic cells. This activation was prevented by the glucocorticoid receptor (GR) antagonist Ru486 and by shRNA-mediated knockdown of the GR. Consistent with this observation, prednisolone treatment of latently infected primary monocytes resulted in HCMV reactivation. Analysis of the phenotype of these cells showed that treatment with GCSs was correlated with differentiation to an anti-inflammatory macrophage-like cell type. On the basis that these observations may be pertinent to HCMV reactivation in post-transplant settings, we retrospectively evaluated the incidence, viral kinetics and viral load of HCMV in liver transplant patients in the presence or absence of GCS treatment. We observed that combination therapy of baseline prednisolone and augmented methylprednisolone, upon organ rejection, significantly increased the incidence of HCMV infection in the intermediate risk group where donor and recipient are both HCMV seropositive (D+R+) to levels comparable with the high risk D+R- group. PMID:25312585

  7. Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: Need for mucosal viral load measurement

    PubMed Central

    Ciccocioppo, Rachele; Racca, Francesca; Paolucci, Stefania; Campanini, Giulia; Pozzi, Lodovica; Betti, Elena; Riboni, Roberta; Vanoli, Alessandro; Baldanti, Fausto; Corazza, Gino Roberto

    2015-01-01

    AIM: To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD). METHODS: A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated. RESULTS: All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/105 cells) than in non-refractory (HCMV 0 and EBV 6 copies/105 cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/105 cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 103 copies/105 cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications. CONCLUSION: Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require

  8. Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis

    PubMed Central

    Hirayama, Yutaka; Ando, Takafumi; Hirooka, Yoshiki; Watanabe, Osamu; Miyahara, Ryoji; Nakamura, Masanao; Yamamura, Takeshi; Goto, Hidemi

    2016-01-01

    AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus (CMV)-associated colitis in patients with active ulcerative colitis (UC). METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis. RESULTS: Multivariate analysis indicated independent associations with the extent of disease (pancolitis) and use of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC (odds ratio = 12.672, 95%CI: 4.210-38.143). CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC. PMID:27014426

  9. Late-onset cytomegalovirus infection complicated by Guillain-Barre syndrome in a kidney transplant recipient: case report and review of the literature.

    PubMed

    Shaban, E; Gohh, R; Knoll, B M

    2016-04-01

    Cytomegalovirus (CMV) infection remains a common infection after solid-organ transplantation. In the general population CMV disease is associated with Guillain-Barre syndrome (GBS), an autoimmune disease leading to an acute peripheral neuropathy, in 1 of 1000 cases. Interestingly, GBS is a rarely observed complication in solid-organ transplant recipients, possibly related to maintenance immunosuppression. We describe a case of CMV infection complicated by GBS in a kidney transplant recipient and review the literature. PMID:26141820

  10. Impaired lymphoid chemokine-mediated migration due to a block on the chemokine receptor switch in human cytomegalovirus-infected dendritic cells.

    PubMed

    Moutaftsi, Magdalena; Brennan, Paul; Spector, Stephen A; Tabi, Zsuzsanna

    2004-03-01

    Dendritic cell (DC) migration from the site of infection to the site of T-cell priming is a crucial event in the generation of antiviral T-cell responses. Here we present to our knowledge the first functional evidence that human cytomegalovirus (HCMV) blocks the migration of infected monocyte-derived DCs toward lymphoid chemokines CCL19 and CCL21. DC migration is blocked by viral impairment of the chemokine receptor switch at the level of the expression of CCR7 molecules. The inhibition occurs with immediate-early-early kinetics, and viral interference with NF-kappaB signaling is likely to be at least partially responsible for the lack of CCR7 expression. DCs which migrate from the infected cultures are HCMV antigen negative, and consequently they do not stimulate HCMV-specific CD8(+) T cells, while CD4(+)-T-cell activation is not impaired. Although CD8(+) T cells can also be activated by alternative antigen presentation mechanisms, the spatial segregation of naive T cells and infected DCs seems a potent mechanism of delaying the generation of primary CD8(+)-T-cell responses and aiding early viral spread. PMID:14990723

  11. Impaired Lymphoid Chemokine-Mediated Migration due to a Block on the Chemokine Receptor Switch in Human Cytomegalovirus-Infected Dendritic Cells

    PubMed Central

    Moutaftsi, Magdalena; Brennan, Paul; Spector, Stephen A.; Tabi, Zsuzsanna

    2004-01-01

    Dendritic cell (DC) migration from the site of infection to the site of T-cell priming is a crucial event in the generation of antiviral T-cell responses. Here we present to our knowledge the first functional evidence that human cytomegalovirus (HCMV) blocks the migration of infected monocyte-derived DCs toward lymphoid chemokines CCL19 and CCL21. DC migration is blocked by viral impairment of the chemokine receptor switch at the level of the expression of CCR7 molecules. The inhibition occurs with immediate-early-early kinetics, and viral interference with NF-κB signaling is likely to be at least partially responsible for the lack of CCR7 expression. DCs which migrate from the infected cultures are HCMV antigen negative, and consequently they do not stimulate HCMV-specific CD8+ T cells, while CD4+-T-cell activation is not impaired. Although CD8+ T cells can also be activated by alternative antigen presentation mechanisms, the spatial segregation of naive T cells and infected DCs seems a potent mechanism of delaying the generation of primary CD8+-T-cell responses and aiding early viral spread. PMID:14990723

  12. Complete resolution of non-necrotizing lung granuloma and pyoderma gangrenosum after restorative proctocolectomy in a woman with severe ulcerative colitis and cytomegalovirus infection.

    PubMed

    Sartini, Alessandro; Bianchini, Marcello; Schepis, Filippo; Marzi, Luca; De Maria, Nicola; Villa, Erica

    2016-02-01

    Here, we report the unusual case of an ulcerative colitis female patient presenting together with cytomegalovirus infection, pyoderma gangrenosum and a noncaseating lung granuloma, both resistant to immunomodulatory drugs which dramatically obtained a clinical stable remission after restorative proctocolectomy. PMID:26862424

  13. Atypical presentation of exophytic herpes simplex virus type 2 with concurrent cytomegalovirus infection: a significant pitfall in diagnosis.

    PubMed

    Garib, George; Hughey, Lauren C; Elmets, Craig A; Cafardi, Jennifer A; Andea, Aleodor A

    2013-05-01

    We report 3 unusual cases of atypical exophytic cutaneous herpes simplex virus (HSV) type 2 with concurrent cytomegalovirus (CMV) infection in immunosuppressed patients and raise awareness to the significant clinical and pathologic challenges in establishing the correct diagnosis. In all the 3 cases, the lesions presented as fungating plaques and nodules with areas of superficial erosion. Initial clinical differential included genital warts, syphilis, versus cutaneous malignancy. All the 3 patients were referred to the dermatology clinic where a combination of cutaneous biopsies, viral cultures of the lesions, polymerase chain reaction, CMV antigenemia, and immunoperoxidase stains for CMV and HSV confirmed the diagnosis of HSV type 2 with concurrent CMV infection. All the 3 patients were treated with oral valganciclovir with significant improvement noted at the follow-up visit. In addition, we review the previously reported HSV/CMV cutaneous coinfection cases. PMID:22534637

  14. Activation of Nucleotide Oligomerization Domain 2 (NOD2) by Human Cytomegalovirus Initiates Innate Immune Responses and Restricts Virus Replication

    PubMed Central

    Kapoor, Arun; Forman, Michael; Arav-Boger, Ravit

    2014-01-01

    Nucleotide-binding oligomerization domain 2 (NOD2) is an important innate immune sensor of bacterial pathogens. Its induction results in activation of the classic NF-κB pathway and alternative pathways including type I IFN and autophagy. Although the importance of NOD2 in recognizing RNA viruses has recently been identified, its role in sensing DNA viruses has not been studied. We report that infection with human cytomegalovirus (HCMV) results in significant induction of NOD2 expression, beginning as early as 2 hours post infection and increasing steadily 24 hours post infection and afterwards. Infection with human herpesvirus 1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is not required for NOD2 induction, a replication competent virion is necessary. Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs) and U373 glioma cells leads to enhanced HCMV replication along with decreased levels of interferon beta (IFN-β) and the pro-inflammatory cytokine, IL8. NOD2 induction in HCMV-infected cells activates downstream NF-κB and interferon pathways supported by reduced nuclear localization of NF-κB and pIRF3 in NOD2 knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication in association with increased levels of IFN-β and IL8. Similarly, transient overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in decreased HCMV replication and enhanced cytokine responses. However, overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's disease, results in enhanced HCMV replication and decreased levels of IFN-β in U373 cells. These results show for the first time that NOD2 plays a significant role in HCMV replication and may provide a model for studies of HCMV recognition by the host cell and HCMV colitis in Crohn's disease. PMID:24671169

  15. A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus

    PubMed Central

    McGregor, Alistair

    2016-01-01

    In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128-131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107–179) and a chimeric HCMV UL128 C-terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model. PMID:27387220

  16. A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus.

    PubMed

    Coleman, Stewart; Choi, K Yeon; Root, Matthew; McGregor, Alistair

    2016-07-01

    In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128-131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107-179) and a chimeric HCMV UL128 C-terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model. PMID:27387220

  17. Proapoptotic Bim regulates antigen-specific NK cell contraction and the generation of the memory NK cell pool after cytomegalovirus infection.

    PubMed

    Min-Oo, Gundula; Bezman, Natalie A; Madera, Sharline; Sun, Joseph C; Lanier, Lewis L

    2014-06-30

    Apoptosis is critical for the elimination of activated lymphocytes after viral infection. Proapoptotic factor Bim (Bcl2l11) controls T lymphocyte contraction and the formation of memory T cells after infection. Natural killer (NK) cells also undergo antigen-driven expansion to become long-lived memory cells after mouse cytomegalovirus (MCMV) infection; therefore, we examined the role of Bim in regulating the MCMV-driven memory NK cell pool. Despite responding similarly early after infection, Bcl2l11(-/-) Ly49H(+) NK cells show impaired contraction and significantly outnumber wild-type (WT) cells after the expansion phase. The inability to reduce the effector pool leads to a larger Bcl2l11(-/-) NK memory subset, which displays a less mature phenotype (CD11b(lo), CD27(+)) and lower levels of NK cell memory-associated markers KLRG1 and Ly6C. Bcl2l11(-/-) memory NK cells demonstrate a reduced response to m157-mediated stimulation and do not protect as effectively as WT memory NK cells in an MCMV challenge model. Thus, Bim-mediated apoptosis drives selective contraction of effector NK cells to generate a pool of mature, MCMV-specific memory cells. PMID:24958849

  18. Comparison of guinea pig cytomegalovirus and guinea pig herpes-like virus: pathogenesis and persistence in experimentally infected animals.

    PubMed Central

    Tenser, R B; Hsiung, G D

    1976-01-01

    The pathogenesis of guinea pig cytomegalovirus (GPCMV) and guinea pig herpes-like virus (GPHLV) in guinea pigs was compared. Animals were inoculated with the two viruses by different routes and sacrificed after varying periods of time. GPCMV was consistently isolated from salivary gland 2 weeks postinoculation and thereafter following intraperitoneal or subcutaneous incoulaton. Virus was less frequently found in other tissues including blood, spleen, and kidney. Intranuclear inclusions were seen in tissue sections of salivary gland after inoculation with GPCMV- infected tissue suspension, but were only rarely found after inoculation with tissue culture virus. In GPHLV-infected guinea pigs, consistent latent infection of leukocytes and other tissues was detected by cocultivation techniques. Intranuclear inclusions were not found in the spleen, salivary gland, or other infected tissues after GPHLV infection with either tissue culture virus or infected tissue suspension. Guinea pigs inoculated with GPCMV produced high titers of specific neutralizing antibody to the homologous virus; those inoculated with GPHLV developed long-term viremia accompanied by minimal neutralizing antibody levels to the virus. Images PMID:178599

  19. Cytomegalovirus Infection May Contribute to the Reduced Immune Function, Growth, Development, and Health of HIV-Exposed, Uninfected African Children

    PubMed Central

    Filteau, Suzanne; Rowland-Jones, Sarah

    2016-01-01

    With increasing access to antiretroviral therapy (ART) in Africa, most children born to HIV-infected mothers are not themselves HIV-infected. These HIV-exposed, uninfected (HEU) children are at increased risk of mortality and have immune, growth, development, and health deficits compared to HIV-unexposed children. HEU children are known to be at higher risk than HIV-unexposed children of acquiring cytomegalovirus (CMV) infection in early life. This risk is largely unaffected by ART and is increased by breastfeeding, which itself is critically important for child health and survival. Early CMV infection, namely in utero or during early infancy, may contribute to reduced growth, altered or impaired immune functions, and sensory and cognitive deficits. We review the evidence that CMV may be responsible for the health impairments of HEU children. There are currently no ideal safe and effective interventions to reduce postnatal CMV infection. If a clinical trial showed proof of the principle that decreasing early CMV infection improved health and development of HEU children, this could provide the impetus needed for the development of better interventions to improve the health of this vulnerable population. PMID:27446087

  20. Toll-like receptor 4 is involved in the cell cycle modulation and required for effective human cytomegalovirus infection in THP-1 macrophages

    SciTech Connect

    Arcangeletti, Maria-Cristina; Germini, Diego; Rodighiero, Isabella; Mirandola, Prisco; De Conto, Flora; Medici, Maria-Cristina; Gatti, Rita; Chezzi, Carlo; Calderaro, Adriana

    2013-05-25

    Suitable host cell metabolic conditions are fundamental for the effective development of the human cytomegalovirus (HCMV) lytic cycle. Indeed, several studies have demonstrated the ability of this virus to interfere with cell cycle regulation, mainly by blocking proliferating cells in G1 or G1/S. In the present study, we demonstrate that HCMV deregulates the cell cycle of THP-1 macrophages (a cell line irreversibly arrested in G0) by pushing them into S and G2 phases. Moreover, we show that HCMV infection of THP-1 macrophages leads to Toll-like receptor 4 (TLR4) activation. Since various studies have indicated TLR4 to be involved in promoting cell proliferation, here we investigate the possible role of TLR4 in the observed HCMV-induced cell cycle perturbation. Our data strongly support TLR4 as a mediator of HCMV-triggered cell cycle activation in THP-1 macrophages favouring, in turn, the development of an efficient viral lytic cycle. - Highlights: ► We studied HCMV infection impact on THP-1 macrophage cell cycle. ► We analysed the role played by Toll-like receptor (TLR) 4 upon HCMV infection. ► HCMV pushes THP-1 macrophages (i.e. resting cells) to re-enter the cell cycle. ► TLR4 pathway inhibition strongly affects the effectiveness of HCMV replication. ► TLR4 pathway inhibition significantly decreases HCMV-induced cell cycle re-entry.

  1. Dual Requirement of Cytokine and Activation Receptor Triggering for Cytotoxic Control of Murine Cytomegalovirus by NK Cells

    PubMed Central

    Pak-Wittel, Melissa A.; Yang, Liping; Schreiber, Robert D.; Yokoyama, Wayne M.

    2015-01-01

    Natural killer (NK) cells play a critical role in controlling murine cytomegalovirus (MCMV) and can mediate both cytokine production and direct cytotoxicity. The NK cell activation receptor, Ly49H, is responsible for genetic resistance to MCMV in C57BL/6 mice. Recognition of the viral m157 protein by Ly49H is sufficient for effective control of MCMV infection. Additionally, during the host response to infection, distinct immune and non-immune cells elaborate a variety of pleiotropic cytokines which have the potential to impact viral pathogenesis, NK cells, and other immune functions, both directly and indirectly. While the effects of various immune deficiencies have been examined for general antiviral phenotypes, their direct effects on Ly49H-dependent MCMV control are poorly understood. To specifically interrogate Ly49H-dependent functions, herein we employed an in vivo viral competition approach to show Ly49H-dependent MCMV control is specifically mediated through cytotoxicity but not IFNγ production. Whereas m157 induced Ly49H-dependent degranulation, efficient cytotoxicity also required either IL-12 or type I interferon (IFN-I) which acted directly on NK cells to produce granzyme B. These studies demonstrate that both of these distinct NK cell-intrinsic mechanisms are integrated for optimal viral control by NK cells. PMID:26720279

  2. Human Cytomegalovirus Infection Interferes with the Maintenance and Differentiation of Trophoblast Progenitor Cells of the Human Placenta

    PubMed Central

    Tabata, Takako; Petitt, Matthew; Zydek, Martin; Fang-Hoover, June; Larocque, Nicholas; Tsuge, Mitsuru; Gormley, Matthew; Kauvar, Lawrence M.

    2015-01-01

    ABSTRACT Human cytomegalovirus (HCMV) is a major cause of birth defects that include severe neurological deficits, hearing and vision loss, and intrauterine growth restriction. Viral infection of the placenta leads to development of avascular villi, edema, and hypoxia associated with symptomatic congenital infection. Studies of primary cytotrophoblasts (CTBs) revealed that HCMV infection impedes terminal stages of differentiation and invasion by various molecular mechanisms. We recently discovered that HCMV arrests earlier stages involving development of human trophoblast progenitor cells (TBPCs), which give rise to the mature cell types of chorionic villi—syncytiotrophoblasts on the surfaces of floating villi and invasive CTBs that remodel the uterine vasculature. Here, we show that viral proteins are present in TBPCs of the chorion in cases of symptomatic congenital infection. In vitro studies revealed that HCMV replicates in continuously self-renewing TBPC lines derived from the chorion and alters expression and subcellular localization of proteins required for cell cycle progression, pluripotency, and early differentiation. In addition, treatment with a human monoclonal antibody to HCMV glycoprotein B rescues differentiation capacity, and thus, TBPCs have potential utility for evaluation of the efficacies of novel antiviral antibodies in protecting and restoring placental development. Our results suggest that HCMV replicates in TBPCs in the chorion in vivo, interfering with the earliest steps in the growth of new villi, contributing to virus transmission and impairing compensatory development. In cases of congenital infection, reduced responsiveness of the placenta to hypoxia limits the transport of substances from maternal blood and contributes to fetal growth restriction. IMPORTANCE Human cytomegalovirus (HCMV) is a leading cause of birth defects in the United States. Congenital infection can result in permanent neurological defects, mental retardation

  3. Risk of congenital cytomegalovirus infection among HIV-exposed uninfected infants is not decreased by maternal nelfinavir use during pregnancy

    PubMed Central

    Gantt, Soren; Leister, Erin; Jacobson, Denise L.; Boucoiran, Isabelle; Huang, Meei-Li; Jerome, Keith R.; Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Burchett, Sandra; Frenkel, Lisa

    2016-01-01

    Background Congenital cytomegalovirus (cCMV) infection is common among infants born to HIV-infected women. Nelfinavir (NFV), an antiretroviral drug that is safe during pregnancy, inhibits CMV replication in vitro at concentrations that standard doses achieve in plasma. We hypothesized that infants born to women receiving NFV for prevention of mother-to-child transmission of HIV (PMTCT) would have a reduced prevalence of cCMV infection. Methods The prevalence of cCMV infection was compared among HIV-uninfected infants whose HIV-infected mothers either received NFV for ≥4 weeks during pregnancy (NFV-exposed) or did not receive any NFV in pregnancy (NFV-unexposed). CMV PCR was performed on infant blood samples collected at <3 weeks from birth. Results Of the 1,255 women included, 314 received NFV for ≥4 weeks during pregnancy and 941 did not receive any NFV during pregnancy. The overall prevalence of cCMV infection in the infants was 2.2%, which did not differ by maternal NFV use. Maternal CD4 T cell counts were inversely correlated with risk of cCMV infection, independent of the time NFV was initiated during gestation. Infants with cCMV infection were born 0.7 weeks earlier (p=0.010) and weighed 170 grams less (p=0.009) than uninfected infants. Conclusion Among HIV-exposed uninfected infants, cCMV infection was associated with adverse perinatal outcomes. NFV use in pregnancy was not associated with protection against cCMV. Safe and effective strategies to prevent cCMV infection are needed. PMID:26519647

  4. Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-05-27

    Accelerated Phase Chronic Myelogenous 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 Acute Promyelocytic Leukemia (M3); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; Chronic Eosinophilic Leukemia; 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 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 Small Lymphocytic Lymphoma; Cytomegalovirus Infection; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Isolated Plasmacytoma of Bone; Monoclonal Gammopathy of Undetermined Significance; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse 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 Small Lymphocytic Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously

  5. Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

    PubMed Central

    Wiener, Jeffrey; Chang, Tiffany S.; Dollard, Sheila C.; Amin, Minal M.; Ellington, Sascha; Kayira, Dumbani; van der Horst, Charles; Jamieson, Denise J.

    2015-01-01

    Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections. PMID:26424831

  6. Viral infections in transfusion-dependent patients with beta-thalassemia major: the predominant role of cytomegalovirus.

    PubMed

    Nigro, G; Lionetti, P; Digilio, G; Multari, G; Vania, A; Midulla, M

    1990-01-01

    For 9 months, 38 transfusion-dependent patients with beta-thalassemia, ranging in age from 3.4 to 19.1 years, were observed for serologic evidence of viral infections, by the collection of serial serum samples. Seventy-six age-matched healthy subjects, two for each patient, were followed as controls. Samples taken at the beginning, middle, and end of the study were tested against 18 viral antigens by complement fixation (CF). In addition, tests for antibodies to HIV, Epstein-Barr virus, hepatitis A virus, and markers for hepatitis B virus were performed. When changes in the antibody titer on CF tests (greater than or equal to 2-fold increase or decrease) or persistently high titers (greater than or equal to 64) were revealed, specific enzyme immunoassays (EIAs) for IgM and IgA antibodies were performed concomitant with CF tests in all sera. When symptomatic infections occurred, viral cultures and/or direct detection of antigens were carried out by immunofluorescence methods, EIA, or latex agglutination tests. Thalassemic patients and controls had similar (p greater than 0.05) overall rates of serologically confirmed viral infections (53 versus 132), but the former group had a higher (p less than 0.01) incidence of cytomegalovirus (CMV) infections (9 versus 4). CMV infections were associated in the thalassemic patients with hepatitis (2 cases), lymphadenitis (2 cases), and upper respiratory tract infection (1 case), while the remaining cases of CMV had a subclinical course. Moreover, the thalassemic patients had a lower (p less than 0.01) incidence of symptomatic infections (27 versus 110) than controls. Therefore, this study showed that both symptomatic and subclinical CMV infections may occur often in thalassemic patients, who otherwise have subclinical viral infections at an overall rate similar to that in healthy subjects. PMID:2173179

  7. Autoimmune response to U1 small nuclear ribonucleoprotein (U1 snRNP) associated with cytomegalovirus infection.

    PubMed

    Newkirk, M M; van Venrooij, W J; Marshall, G S

    2001-01-01

    The induction of autoantibodies to U1 small nuclear ribonucleoprotein (U1 snRNP) complexes is not well understood. We present evidence that healthy individuals with cytomegalovirus (CMV) infection have an increased frequency and quantity of antibodies to ribonucleoprotein, directed primarily against the U1-70k protein. A significant association between the presence of antibodies to CMV and antibodies to the total RNP targeted by the immune response to the spliceosome (to both the Sm and RNP; Sm/RNP) was found for patients with systemic lupus erythematosus (SLE) but not those with mixed connective-tissue disease. CMV thus may play a role in inducing autoimmune responses in a subset of patients with systemic lupus erythematosus. PMID:11438044

  8. Data correlations between gender, cytomegalovirus infection and T cells, NK cells, and soluble immune mediators in elderly humans.

    PubMed

    Al-Attar, Ahmad; Presnell, Steven R; Peterson, Charlotte A; Thomas, D Travis; Lutz, Charles T

    2016-09-01

    We describe a cohort of 50 elderly subjects, age at least 70 years. We present gender-specific findings in T lymphocyte markers and soluble immune mediators. We show the correlation between cytomegalovirus infection status with CD56(dim) NK cell responses to a variety of stimuli and with CD56(bright)/CD56(dim) NK cell ratio. We also present the correlation of retinol binding protein (RBP)-4 plasma levels with NK cell responses and we explore the relationship between gender and adiponectin, 25(OH)D (vitamin D), and RBP4 in affecting CD56(dim) NK cell responses. These data are discussed in Al-Attar et al. (2016) [1]. PMID:27508213

  9. Infection and Cardiovascular Disease

    ClinicalTrials.gov

    2016-02-17

    Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Heart Diseases; Myocardial Infarction; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Atherosclerosis

  10. [Consensus document from the Spanish Society of Paediatric Infectious Diseases (SEIP) on the diagnosis and treatment of congenital cytomegalovirus infection].

    PubMed

    Baquero-Artigao, F

    2009-12-01

    Cytomegalovirus (CMV) is the leading cause of congenital infection in developed countries, affecting 0.3 to 0.6% of all live births in Europe. Primary CMV infection occurs in 1 to 4% of seronegative women during pregnancy and may be transmitted to the fetus in 40% of cases. Up to 10% of intrauterine CMV infections result in symptomatic congenital disease at birth. Half of these children and 13% of those born with asymptomatic infection will develop long-term sequelae, especially neurosensory hearing loss and mental retardation. Accurate diagnosis of primary maternal and fetal infection is now possible using the avidity index of anti-CMV IgG and virological testing to detect the virus in amniotic fluid. Symptomatic congenital infection may be preventable using CMV hyperimmune globulin during pregnancy. The gold standard for diagnosis of congenital CMV infection is the detection of the virus in urine within the first 2 weeks of life by rapid cell culture techniques (shell vial) or nucleic acid amplification of viral DNA (PCR). Retrospective diagnosis can be achieved by detection of viral DNA by PCR in dried blood spots (Guthrie card) collected on filter paper in the first days of life. Currently available drugs for the treatment of congenital CMV include ganciclovir and its oral prodrug valganciclovir. Treatment with intravenous ganciclovir for six weeks may prevent hearing deterioration in children with symptomatic congenital CMV infection and central nervous system involvement. Valganciclovir may be an excellent alternative because of its good bio-availability, providing plasma concentrations similar to those achieved with intravenous ganciclovir. PMID:19815469