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  1. Multiple mechanisms contribute to impairment of type 1 interferon production during chronic lymphocytic choriomeningitis virus infection of mice.

    PubMed

    Lee, Lian Ni; Burke, Shannon; Montoya, Maria; Borrow, Persephone

    2009-06-01

    Type 1 IFNs, innate cytokines with important effector and immunomodulatory properties, are rapidly induced in the acute phase of many virus infections; however, this is generally a transient response that is not sustained during virus persistence. To gain insight into mechanisms that can contribute to down-regulation of type 1 IFN production during virus persistence, we analyzed type 1 IFN production during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection. High-level type 1 IFN production was transiently up-regulated in cells including plasmacytoid and conventional dendritic cells (DCs) following LCMV infection of mice, but LCMV persistence was associated with only low-level type 1 IFN production. Nonetheless, chronically infected mice were able to up-regulate type 1 IFN production in response to TLR3, 7, and 9 ligands, albeit less efficiently than uninfected mice. Splenic DC numbers in mice chronically infected with LCMV were decreased, and the remaining cells exhibited a reduced response to TLR stimulation. LCMV-infected cell lines efficiently up-regulated type 1 IFN production following TLR ligation and infection with a DNA virus, but exhibited a defect in type 1 IFN induction following infection with Sendai, an RNA virus. This block in type 1 IFN production by infected cells, together with abnormalities in DC numbers and functions, likely contribute to the low-level type 1 IFN production in mice chronically infected with LCMV. Impairment of type 1 IFN production may both promote virus persistence and impact on host immunocompetence. Understanding the mechanisms involved may assist in development of strategies for control of virus persistence and superinfection. PMID:19454715

  2. Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice.

    PubMed

    Park, Hyo Jin; Oh, Ji Hoon; Ha, Sang-Jun

    2016-01-01

    Regulatory T (Treg) cells, which express Foxp3 as a transcription factor, are subsets of CD4(+) T cells. Treg cells play crucial roles in immune tolerance and homeostasis maintenance by regulating the immune response. The primary role of Treg cells is to suppress the proliferation of effector T (Teff) cells and the production of cytokines such as IFN-γ, TNF-α, and IL-2. It has been demonstrated that Treg cells' ability to inhibit the function of Teff cells is enhanced during persistent pathogen infection and cancer development. To clarify the function of Treg cells under resting or inflamed conditions, a variety of in vitro suppression assays using mouse or human Treg cells have been devised. The main aim of this study is to develop a method to compare the differences in phenotype and suppressive function between resting and activated Treg cells. To isolate activated Treg cells, mice were infected with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13), a chronic strain of LCMV. Treg cells isolated from the spleen of LCMV CL13-infected mice exhibited both the activated phenotype and enhanced suppressive activity compared with resting Treg cells isolated from naïve mice. Here, we describe the basic protocol for ex vivo phenotype analysis to distinguish activated Treg cells from resting Treg cells. Furthermore, we describe a protocol for the measurement of the suppressive activity of fully activated Treg cells. PMID:27404802

  3. Uncovering subdominant cytotoxic T-lymphocyte responses in lymphocytic choriomeningitis virus-infected BALB/c mice.

    PubMed Central

    van der Most, R G; Concepcion, R J; Oseroff, C; Alexander, J; Southwood, S; Sidney, J; Chesnut, R W; Ahmed, R; Sette, A

    1997-01-01

    The cytotoxic T-lymphocyte response against lymphocytic choriomeningitis virus (LCMV) in BALB/c mice is predominantly directed against a single, Ld-restricted epitope in the viral nucleoprotein (residues 118 to 126). To investigate whether any Kd/Dd-restricted responses were activated but did not expand during the primary response, we used a BALB/c mutant, BALB/c-H-2dm2, which does not express the Ld molecule. Splenocytes from LCMV-infected BALB/c mice were transferred into irradiated BALB/c-H-2dm2 mice and rechallenged with LCMV. Thus, they were exposed to an antigenic stimulus without the involvement of the immunodominant Ld-restricted epitope. In this adoptive transfer model, the donor splenocytes protected the recipient mice against chronic LCMV infection by mounting a potent Kd- and/or Dd-restricted secondary antiviral response. Analysis of a panel of Kd binding LCMV peptides revealed that residues 283 to 291 from the viral glycoprotein (GP(283-291)) comprise a major new epitope in the adoptive transfer model. Because the donor splenocytes were first activated during the primary infection in BALB/c mice, the GP(283-291) epitope is a subdominant epitope in BALB/c mice that becomes dominant after rechallenge in BALB/c-H-2dm2 mice. This study makes two points. First, it shows that subdominant CTL responses can be protective, and second, it provides a general experimental approach for uncovering subdominant CTL responses in vivo. This strategy can be used to identify subdominant T-cell responses in other systems. PMID:9188577

  4. Rapid activation of spleen dendritic cell subsets following lymphocytic choriomeningitis virus infection of mice: analysis of the involvement of type 1 IFN.

    PubMed

    Montoya, Maria; Edwards, Matthew J; Reid, Delyth M; Borrow, Persephone

    2005-02-15

    In this study, we report the dynamic changes in activation and functions that occur in spleen dendritic cell (sDC) subsets following infection of mice with a natural murine pathogen, lymphocytic choriomeningitis virus (LCMV). Within 24 h postinfection (pi), sDCs acquired the ability to stimulate naive LCMV-specific CD8+ T cells ex vivo. Conventional (CD11chigh CD8+ and CD4+) sDC subsets rapidly up-regulated expression of costimulatory molecules and began to produce proinflammatory cytokines. Their tendency to undergo apoptosis ex vivo simultaneously increased, and in vivo the number of conventional DCs in the spleen decreased markedly, dropping approximately 2-fold by day 3 pi. Conversely, the number of plasmacytoid (CD11clowB220+) DCs in the spleen increased, so that they constituted almost 40% of sDCs by day 3 pi. Type 1 IFN production was up-regulated in plasmacytoid DCs by 24 h pi. Analysis of DC activation and maturation in mice unable to respond to type 1 IFNs implicated these cytokines in driving infection-associated phenotypic activation of conventional DCs and their enhanced tendency to undergo apoptosis, but also indicated the existence of type 1 IFN-independent pathways for the functional maturation of DCs during LCMV infection. PMID:15699111

  5. West Nile Virus Infection in the Central Nervous System

    PubMed Central

    Winkelmann, Evandro R.; Luo, Huanle; Wang, Tian

    2016-01-01

    West Nile virus (WNV), a neurotropic single-stranded flavivirus has been the leading cause of arboviral encephalitis worldwide.  Up to 50% of WNV convalescent patients in the United States were reported to have long-term neurological sequelae.  Neither antiviral drugs nor vaccines are available for humans.  Animal models have been used to investigate WNV pathogenesis and host immune response in humans.  In this review, we will discuss recent findings from studies in animal models of WNV infection, and provide new insights on WNV pathogenesis and WNV-induced host immunity in the central nervous system. PMID:26918172

  6. Switch to Raltegravir From Protease Inhibitor or Nonnucleoside Reverse-Transcriptase Inhibitor Does not Reduce Visceral Fat In Human Immunodeficiency Virus-Infected Women With Central Adiposity.

    PubMed

    Lake, Jordan E; McComsey, Grace A; Hulgan, Todd; Wanke, Christine A; Mangili, Alexandra; Walmsley, Sharon L; Currier, Judith S

    2015-04-01

    Human immunodeficiency virus-infected women with central adiposity switched to raltegravir-based antiretroviral therapy immediately or after 24 weeks. No statistically significant changes in computed tomography-quantified visceral adipose tissue (VAT) or subcutaneous fat were observed, although 48 weeks of raltegravir was associated with a 6.4% VAT decline. Raltegravir for 24 weeks was associated with improvements in lipids. PMID:26380350

  7. HIV and hepatitis C virus infections among hanka injection drug users in central Ukraine: a cross-sectional survey

    PubMed Central

    Dumchev, Kostyantyn V; Soldyshev, Ruslan; Qian, Han-Zhu; Zezyulin, Olexandr O; Chandler, Susan D; Slobodyanyuk, Pavel; Moroz, Larisa; Schumacher, Joseph E

    2009-01-01

    Background Ukraine has experienced an increase in injection drug use since the 1990s. An increase in HIV and hepatitis C virus infections has followed, but not measures of prevalence and risk factors. The purposes of this study are to estimate the prevalence of HIV, HCV, and co-infection among injection drug users (IDUs) in central Ukraine and to describe risk factors for HIV and HCV. Methods A sample of 315 IDUs was recruited using snowball sampling for a structured risk interview and HIV/HCV testing (81.9% male, 42% single, average age 28.9 years [range = 18 to 55]). Results HIV and HCV antibodies were detected in 14.0% and 73.0%, respectively, and 12.1% were seropositive for both infections. The most commonly used drug was hanka, home-made from poppy straw and often mixed with other substances including dimedrol, diazepines, and hypnotics. The average period of injecting was 8.5 years; 62.5% reported past-year sharing needles or injection equipment, and 8.0% shared with a known HIV-positive person. More than half (51.1%) reported multiple sexual partners, 12.9% buying or selling sex, and 10.5% exchanging sex and drugs in the past year. Those who shared with HIV positive partners were 3.4 times more likely to be HIV positive than those who did not. Those who front- or back-loaded were 4 times more likely to be HCV positive than those who did not. Conclusion Harm reduction, addiction treatment and HIV prevention programs should address risk factors to stop further spread of both HIV and HCV among IDUs and to the general population in central Ukraine. PMID:19698166

  8. Prevalence of hepatitis C virus infection among recyclable waste collectors in Central-West Brazil

    PubMed Central

    Marinho, Thaís Augusto; Lopes, Carmen Luci Rodrigues; Teles, Sheila Araújo; Reis, Nádia Rúbia Silva; Carneiro, Megmar Aparecida dos Santos; de Andrade, Andreia Alves; Martins, Regina Maria Bringel

    2013-01-01

    The prevalence of hepatitis C virus (HCV) in a population of recyclable waste collectors (n = 431) was assessed using a cross-sectional survey in all 15 cooperatives in the city of Goiânia, Central-West Brazil. The HCV prevalence was 1.6% (95% confidence interval: 0.6-3.6) and a history of sexually transmitted infections was independently associated with this infection. HCV RNA (corresponding to genotype 1; subtypes 1a and 1b) was detected in five/seven anti-HCV-positive samples. Although the study population reported a high rate (47.3%) of sharps and needle accidents, HCV infection was not more frequent in recyclable waste collectors than in the general Brazilian population. PMID:23828009

  9. West Nile virus infection rates and avian serology in east-central Illinois.

    PubMed

    Lampman, Richard L; Krasavin, Nina M; Ward, Mike P; Beveroth, Tara A; Lankau, Emily W; Alto, Barry W; Muturi, Ephantus; Novak, Robert J

    2013-06-01

    Understanding the geographic role of different species of mosquito vectors and vertebrate hosts in West Nile virus (WNV) transmission cycles can facilitate the development and implementation of targeted surveillance and control measures. This study examined the relationship between WNV-antibody rates in birds and mosquito infection rates and bloodfeeding patterns in east-central Illinois. The earliest detection of WNV-RNA by reverse transcription-polymerase chain reaction TaqMan was from Culex restuans; however, amplification typically coincided with an increase in abundance of Cx. pipiens. Trap type influenced annual estimates of infection rates in Culex species, as well as estimation of blood meal source. Bird species with the highest WNV-antibody rates (i.e., Mourning Doves [Zenaida macroura], Northern Cardinals [Cardinalis cardinalis], American Robins [Turdus migratorius], and House Sparrows [Passer domesticus]) were also the common species found in Culex blood meals. Although antibody rates were not directly proportional to estimated avian abundance, the apparent availability of mammal species did influence proportion of mammal to bird blood meals. Antibody prevalence in the American Robin was lower than expected based on the strong attraction of Culex to American Robins for blood meals. Age-related differences in serology were evident, antibody rates increased in older groups of robins and sparrows, whereas 1st-year hatch and older adults of Mourning Doves and Northern Cardinals had equally high rates of antibody-positive serum samples. The vector and host interactions observed in east-central Illinois (Champaign County), an urban area surrounded by agriculture, are compared to studies in the densely population areas of southern Cook County. PMID:23923325

  10. Dengue virus infection-enhancing antibody activities against Indonesian strains in inhabitants of central Thailand.

    PubMed

    Yamanaka, Atsushi; Oddgun, Duangjai; Chantawat, Nantarat; Okabayashi, Tamaki; Ramasoota, Pongrama; Churrotin, Siti; Kotaki, Tomohiro; Kameoka, Masanori; Soegijanto, Soegeng; Konishi, Eiji

    2016-04-01

    Dengue virus (DENV) infection-enhancing antibodies are a hypothetic factor to increase the dengue disease severity. In this study, we investigated the enhancing antibodies against Indonesian strains of DENV-1-4 in 50 healthy inhabitants of central Thailand (Bangkok and Uthai Thani). Indonesia and Thailand have seen the highest dengue incidence in Southeast Asia. The infection history of each subject was estimated by comparing his/her neutralizing antibody titers against prototype DENV-1-4 strains. To resolve the difficulty in obtaining foreign live viruses for use as assay antigens, we used a recombinant system to prepare single-round infectious dengue viral particles based on viral sequence information. Irrespective of the previously infecting serotype(s), most serum samples showed significantly higher enhancement titers against Indonesian DENV-2 strains than against Thai DENV-2 strains, whereas the opposite effect was observed for the DENV-3 strains. Equivalent enhancing activities were observed against both DENV-1 and DENV-4. These results suggest that the genotype has an impact on enhancing antibody activities against DENV-2 and DENV-3, because the predominant circulating genotypes of each serotype differ between Indonesia and Thailand. PMID:26645957

  11. Varicella-zoster virus infections of the central nervous system – Prognosis, diagnostics and treatment.

    PubMed

    Grahn, Anna; Studahl, Marie

    2015-09-01

    Both varicella and herpes zoster that are caused by varicella-zoster virus (VZV), are associated with central nervous system disease. Since the introduction of polymerase chain reaction, the opportunity to detect the virus in cerebrospinal fluid (CSF) has improved dramatically. As a result VZV is diagnosed as one of the most common viruses causing CNS disease and it has become evident that this disease includes a wide spectrum of different CNS manifestations. The most evaluated CNS manifestations are encephalitis which is associated with both varicella and herpes zoster and, cerebellitis which occurs predominantly in children with varicella. Other manifestations have been less widely investigated. The incidence of cerebrovascular disease caused by VZV has been only scarcely studied and, in addition, some data indicate that vasculitis might also be involved in other VZV CNS manifestations such as herpes zoster-associated encephalitis. For this reason, VZV CNS infection must be suspected in several CNS syndromes and diagnostics should be based on CSF analysis for detection of VZV DNA by PCR and/or intrathecal antibody production. The prognosis is reported as favourable in children but few follow-up studies are available. Moreover, in adults, the prognosis is reported to be good in overall terms, but later studies indicate more serious neurological sequelae including cognition. Despite considerable mortality and morbidity, so far also in vaccinating countries, few treatment studies are available. Further treatment studies including assessments of neurological and cognitive sequelae, are warranted. PMID:26073188

  12. Reactive oxygen species delay control of lymphocytic choriomeningitis virus

    PubMed Central

    Lang, P A; Xu, H C; Grusdat, M; McIlwain, D R; Pandyra, A A; Harris, I S; Shaabani, N; Honke, N; Kumar Maney, S; Lang, E; Pozdeev, V I; Recher, M; Odermatt, B; Brenner, D; Häussinger, D; Ohashi, P S; Hengartner, H; Zinkernagel, R M; Mak, T W; Lang, K S

    2013-01-01

    Cluster of differentiation (CD)8+ T cells are like a double edged sword during chronic viral infections because they not only promote virus elimination but also induce virus-mediated immunopathology. Elevated levels of reactive oxygen species (ROS) have been reported during virus infections. However, the role of ROS in T-cell-mediated immunopathology remains unclear. Here we used the murine lymphocytic choriomeningitis virus to explore the role of ROS during the processes of virus elimination and induction of immunopathology. We found that virus infection led to elevated levels of ROS producing granulocytes and macrophages in virus-infected liver and spleen tissues that were triggered by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Lack of the regulatory subunit p47phox of the NADPH oxidase diminished ROS production in these cells. While CD8+ T cells exhibited ROS production that was independent of NADPH oxidase expression, survival and T-cell function was elevated in p47phox-deficient (Ncf1−/−) mice. In the absence of p47phox, enhanced T-cell immunity promoted virus elimination and blunted corresponding immunopathology. In conclusion, we find that NADPH-mediated production of ROS critically impairs the immune response, impacting elimination of virus and outcome of liver cell damage. PMID:23328631

  13. [ZIKA--VIRUS INFECTION].

    PubMed

    Velev, V

    2016-01-01

    This review summarizes the knowledge of the scientific community for Zika-virus infection. It became popular because of severe congenital damage causes of CNS in newborns whose mothers are infected during pregnancy, as well as the risk of pandemic distribution. Discusses the peculiarities of the biology and ecology of vectors--blood-sucking mosquitoes Aedes; stages in the spread of infection and practical problems which caused during pregnancy. Attention is paid to the recommendations that allow leading national and international medical organizations to deal with the threat Zika-virus infection. PMID:27509655

  14. Seroprevalence and Risk Factors for Hepatitis C Virus Infection among General Population in Central Region of Yemen

    PubMed Central

    Gacche, Rajesh N.; Al-Mohani, Sadiq K.

    2012-01-01

    Background. Hepatitis C virus (HCV) represents a major worldwide public health problem. Though several studies from Yemen have provided an estimate of the prevalence of this viral infection, there exist only few studies which reflect the status in the general population. Aim. The present study was designed to investigate the prevalence of hepatitis C infection among general population in central region of Yemen. Methods. The study population comprised 2,379 apparently healthy subjects who were screened for hepatitis C antibodies (HCV Abs) status using ELISA quantitative technique. Seroprevalence rate of seropositive subjects was calculated and stratified by age, sex, educational level, and monthly income. Results. The study showed that out of 2,379 subjects, 31 (1.3%) were HCV Abs positive. Higher prevalence of HCV Abs was found among females, 24 (1.01%), than males, 7 (0.29%). The age specific prevalence rose from 00 (0.00%) in subjects aged ≤14 years to a maximum of 9 (0.38%) in subjects aged ≥55 years. The prevalence of HCV Abs was more prevalent in illiterate subjects and increased with decreasing monthly income. Conclusion. It was found that variables including age and educational level were significantly associated with HCV Ab positivity and not associated with gender and monthly income. PMID:23320156

  15. DELAYED DENSITY-DEPENDENT PREVALENCE OF SIN NOMBRE VIRUS INFECTION IN DEER MICE (PEROMYSCUS MANICULATUS) IN CENTRAL AND WESTERN MONTANA

    PubMed Central

    Carver, Scott; Trueax, Jeremy T.; Douglass, Richard; Kuenzi, Amy

    2011-01-01

    Understanding how transmission of zoonoses takes place within reservoir populations, such as Sin Nombre virus (SNV) among deer mice (Peromyscus maniculatus), is important in determining the risk of exposure to other hosts, including humans. In this study, we examined the relationship between deer mouse populations and the prevalence of antibodies to SNV, a system where the effect of host population abundance on transmission is debated. We examined the relationship between abundance of deer mice in late summer–early autumn and SNV antibody prevalence the following spring–early summer (termed delayed density-dependent [DDD] prevalence of infection) at both regional and local scales, using 12 live-trapping grids for 11–14 yr, across central and western Montana. When all trapping grids were combined (regional scale), there was a significant DDD relationship for individual months and when months within seasons were averaged. However, within individual grids (local scale), evidence of DDD prevalence of infection was observed consistently at only one location. These findings suggest that, although there is evidence of DDD prevalence of infection at regional scales, it is not always apparent at local scales, possibly because the regional pattern of DDD infection prevalence is driven by differences in abundance and prevalence among sites, rather than in autumn-spring delays. Transmission of SNV may be more complex than the original hypothesis of autumn-spring delayed density dependence suggests. This complexity is also supported by recent modeling studies. Empirical investigations are needed to determine the duration and determinants of time-lagged abundance and antibody prevalence. Our study suggests predicting local, human exposure risk to SNV in spring, based on deer mouse abundance in autumn, is unlikely to be a reliable public health tool, particularly at local scales. PMID:21269997

  16. Viral Infection of the Central Nervous System and Neuroinflammation Precede Blood-Brain Barrier Disruption during Japanese Encephalitis Virus Infection

    PubMed Central

    Li, Fang; Wang, Yueyun; Yu, Lan; Cao, Shengbo; Wang, Ke; Yuan, Jiaolong; Wang, Chong; Wang, Kunlun; Fu, Zhen F.

    2015-01-01

    ABSTRACT Japanese encephalitis is an acute zoonotic, mosquito-borne disease caused by Japanese encephalitis virus (JEV). Japanese encephalitis is characterized by extensive inflammation in the central nervous system (CNS) and disruption of the blood-brain barrier (BBB). However, the pathogenic mechanisms contributing to the BBB disruption are not known. Here, using a mouse model of intravenous JEV infection, we show that virus titers increased exponentially in the brain from 2 to 5 days postinfection. This was accompanied by an early, dramatic increase in the level of inflammatory cytokines and chemokines in the brain. Enhancement of BBB permeability, however, was not observed until day 4, suggesting that viral entry and the onset of inflammation in the CNS occurred prior to BBB damage. In vitro studies revealed that direct infection with JEV could not induce changes in the permeability of brain microvascular endothelial cell monolayers. However, brain extracts derived from symptomatic JEV-infected mice, but not from mock-infected mice, induced significant permeability of the endothelial monolayer. Consistent with a role for inflammatory mediators in BBB disruption, the administration of gamma interferon-neutralizing antibody ameliorated the enhancement of BBB permeability in JEV-infected mice. Taken together, our data suggest that JEV enters the CNS, propagates in neurons, and induces the production of inflammatory cytokines and chemokines, which result in the disruption of the BBB. IMPORTANCE Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia, resulting in 70,000 cases each year, in which approximately 20 to 30% of cases are fatal, and a high proportion of patients survive with serious neurological and psychiatric sequelae. Pathologically, JEV infection causes an acute encephalopathy accompanied by BBB dysfunction; however, the mechanism is not clear. Thus, understanding the mechanisms of BBB disruption in JEV infection is important

  17. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection. PMID:27486731

  18. Zika Virus Infection and Microcephaly.

    PubMed

    Millichap, J Gordon

    2016-01-01

    A Task Force established by the Brazil Ministry of Health investigated the possible association of microcephaly with Zika virus infection during pregnancy and a registry for microcephaly cases among women suspected to have had Zika virus infection during pregnancy. PMID:27004142

  19. Monkeypox Virus Infections

    MedlinePlus

    ... occurs mostly in central and western Africa. Wild rodents and squirrels carry it, but it is called monkeypox because scientists saw it first in lab monkeys. In 2003, it was reported in prairie dogs and humans in the U.S. Centers for Disease Control and Prevention

  20. Mice with different susceptibility to tick-borne encephalitis virus infection show selective neutralizing antibody response and inflammatory reaction in the central nervous system

    PubMed Central

    2013-01-01

    Background The clinical course of tick-borne encephalitis (TBE), a disease caused by TBE virus, ranges from asymptomatic or mild influenza-like infection to severe debilitating encephalitis or encephalomyelitis. Despite the medical importance of this disease, some crucial steps in the development of encephalitis remain poorly understood. In particular, the basis of the disease severity is largely unknown. Methods TBE virus growth, neutralizing antibody response, key cytokine and chemokine mRNA production and changes in mRNA levels of cell surface markers of immunocompetent cells in brain were measured in mice with different susceptibilities to TBE virus infection. Results An animal model of TBE based on BALB/c-c-STS/A (CcS/Dem) recombinant congenic mouse strains showing different severities of the infection in relation to the host genetic background was developed. After subcutaneous inoculation of TBE virus, BALB/c mice showed medium susceptibility to the infection, STS mice were resistant, and CcS-11 mice were highly susceptible. The resistant STS mice showed lower and delayed viremia, lower virus production in the brain and low cytokine/chemokine mRNA production, but had a strong neutralizing antibody response. The most sensitive strain (CcS-11) failed in production of neutralizing antibodies, but exhibited strong cytokine/chemokine mRNA production in the brain. After intracerebral inoculation, all mouse strains were sensitive to the infection and had similar virus production in the brain, but STS mice survived significantly longer than CcS-11 mice. These two strains also differed in the expression of key cytokines/chemokines, particularly interferon gamma-induced protein 10 (IP-10/CXCL10) and monocyte chemotactic protein-1 (MCP-1/CCL2) in the brain. Conclusions Our data indicate that the genetic control is an important factor influencing the clinical course of TBE. High neutralizing antibody response might be crucial for preventing host fatality, but high

  1. [Zika virus infection during pregnancy].

    PubMed

    Picone, O; Vauloup-Fellous, C; D'Ortenzio, E; Huissoud, C; Carles, G; Benachi, A; Faye, A; Luton, D; Paty, M-C; Ayoubi, J-M; Yazdanpanah, Y; Mandelbrot, L; Matheron, S

    2016-05-01

    A Zika virus epidemic is currently ongoing in the Americas. This virus is linked to congenital infections with potential severe neurodevelopmental dysfunction. However, incidence of fetal infection and whether this virus is responsible of other fetal complications are still unknown. National and international public health authorities recommend caution and several prevention measures. Declaration of Zika virus infection is now mandatory in France. Given the available knowledge on Zika virus, we suggest here a review of the current recommendations for management of pregnancy in case of suspicious or infection by Zika virus in a pregnant woman. PMID:27079865

  2. Probiotics in respiratory virus infections.

    PubMed

    Lehtoranta, L; Pitkäranta, A; Korpela, R

    2014-08-01

    Viral respiratory infections are the most common diseases in humans. A large range of etiologic agents challenge the development of efficient therapies. Research suggests that probiotics are able to decrease the risk or duration of respiratory infection symptoms. However, the antiviral mechanisms of probiotics are unclear. The purpose of this paper is to review the current knowledge on the effects of probiotics on respiratory virus infections and to provide insights on the possible antiviral mechanisms of probiotics. A PubMed and Scopus database search was performed up to January 2014 using appropriate search terms on probiotic and respiratory virus infections in cell models, in animal models, and in humans, and reviewed for their relevance. Altogether, thirty-three clinical trials were reviewed. The studies varied highly in study design, outcome measures, probiotics, dose, and matrices used. Twenty-eight trials reported that probiotics had beneficial effects in the outcome of respiratory tract infections (RTIs) and five showed no clear benefit. Only eight studies reported investigating viral etiology from the respiratory tract, and one of these reported a significant decrease in viral load. Based on experimental studies, probiotics may exert antiviral effects directly in probiotic-virus interaction or via stimulation of the immune system. Although probiotics seem to be beneficial in respiratory illnesses, the role of probiotics on specific viruses has not been investigated sufficiently. Due to the lack of confirmatory studies and varied data available, more randomized, double-blind, and placebo-controlled trials in different age populations investigating probiotic dose response, comparing probiotic strains/genera, and elucidating the antiviral effect mechanisms are necessary. PMID:24638909

  3. Early blood profiles of virus infection in a monkey model for Lassa fever.

    PubMed

    Djavani, Mahmoud M; Crasta, Oswald R; Zapata, Juan Carlos; Fei, Zhangjun; Folkerts, Otto; Sobral, Bruno; Swindells, Mark; Bryant, Joseph; Davis, Harry; Pauza, C David; Lukashevich, Igor S; Hammamieh, Rasha; Jett, Marti; Salvato, Maria S

    2007-08-01

    Acute arenavirus disease in primates, like Lassa hemorrhagic fever in humans, begins with flu-like symptoms and leads to death approximately 2 weeks after infection. Our goal was to identify molecular changes in blood that are related to disease progression. Rhesus macaques (Macaca mulatta) infected intravenously with a lethal dose of lymphocytic choriomeningitis virus (LCMV) provide a model for Lassa virus infection of humans. Blood samples taken before and during the course of infection were used to monitor gene expression changes that paralleled disease onset. Changes in blood showed major disruptions in eicosanoid, immune response, and hormone response pathways. Approximately 12% of host genes alter their expression after LCMV infection, and a subset of these genes can discriminate between virulent and non-virulent LCMV infection. Major transcription changes have been given preliminary confirmation by quantitative PCR and protein studies and will be valuable candidates for future validation as biomarkers for arenavirus disease. PMID:17522210

  4. Early Blood Profiles of Virus Infection in a Monkey Model for Lassa Fever▿ †

    PubMed Central

    Djavani, Mahmoud M.; Crasta, Oswald R.; Zapata, Juan Carlos; Fei, Zhangjun; Folkerts, Otto; Sobral, Bruno; Swindells, Mark; Bryant, Joseph; Davis, Harry; Pauza, C. David; Lukashevich, Igor S.; Hammamieh, Rasha; Jett, Marti; Salvato, Maria S.

    2007-01-01

    Acute arenavirus disease in primates, like Lassa hemorrhagic fever in humans, begins with flu-like symptoms and leads to death approximately 2 weeks after infection. Our goal was to identify molecular changes in blood that are related to disease progression. Rhesus macaques (Macaca mulatta) infected intravenously with a lethal dose of lymphocytic choriomeningitis virus (LCMV) provide a model for Lassa virus infection of humans. Blood samples taken before and during the course of infection were used to monitor gene expression changes that paralleled disease onset. Changes in blood showed major disruptions in eicosanoid, immune response, and hormone response pathways. Approximately 12% of host genes alter their expression after LCMV infection, and a subset of these genes can discriminate between virulent and nonvirulent LCMV infection. Major transcription changes have been given preliminary confirmation by quantitative PCR and protein studies and will be valuable candidates for future validation as biomarkers for arenavirus disease. PMID:17522210

  5. Recurrent neonatal herpes simplex virus infection with central nervous system disease after completion of a 6-month course of suppressive therapy: Case report.

    PubMed

    Kato, Koji; Hara, Shinya; Kawada, Jun-Ichi; Ito, Yoshinori

    2015-12-01

    A boy at 12 days of age developed neonatal herpes simplex virus (HSV) type 2 infection with central nervous system (CNS) disease. After a 21-day course of high-dose intravenous acyclovir, the patient recovered with negative results for HSV DNA in serum and cerebrospinal fluid. Two weeks after a 6-month course of oral valacyclovir suppressive therapy with negative virological assessment, the disease recurred. Another 21-day course of intravenous acyclovir and subsequent 1-year course of oral suppressive therapy were completed. He showed mild developmental delay in language-social skills at 18 months of age. Although recurrences of neonatal HSV infection with CNS disease after suppressive therapy are uncommon, both clinical and virological assessments at the end of the suppressive therapy may be required. Administration of extended long-term suppressive ACV therapy should be considered to reduce the rate of recurrence. PMID:26390826

  6. The assessment of risk factors for the Central/East African Genotype of chikungunya virus infections in the state of Kelantan: a case control study in Malaysia

    PubMed Central

    2013-01-01

    cases were treated as outpatient, only 7.5% needed hospitalization. The CHIKV infection was attributable to central/east African genotype CHIKV. Conclusions In this study, cross border activity was not a significant risk factor although Thailand and Malaysia shared the same CHIKV genotype during the episode of infections. PMID:23656634

  7. Avian Influenza A Virus Infections in Humans

    MedlinePlus

    ... Research Making a Candidate Vaccine Virus Related Links Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... Submit What's this? Submit Button Past Newsletters Avian Influenza A Virus Infections in Humans Language: English Españ ...

  8. Uveitis Associated with Zika Virus Infection.

    PubMed

    Furtado, João M; Espósito, Danillo L; Klein, Taline M; Teixeira-Pinto, Tomás; da Fonseca, Benedito A

    2016-07-28

    An adult patient recovered from acute Zika virus infection, but ocular symptoms subsequently developed. Anterior uveitis was diagnosed, and Zika virus was identified in the aqueous humor. PMID:27332784

  9. Toso regulates differentiation and activation of inflammatory dendritic cells during persistence-prone virus infection

    PubMed Central

    Lang, P A; Meryk, A; Pandyra, A A; Brenner, D; Brüstle, A; Xu, H C; Merches, K; Lang, F; Khairnar, V; Sharma, P; Funkner, P; Recher, M; Shaabani, N; Duncan, G S; Duhan, V; Homey, B; Ohashi, P S; Häussinger, D; Knolle, P A; Honke, N; Mak, T W; Lang, K S

    2015-01-01

    During virus infection and autoimmune disease, inflammatory dendritic cells (iDCs) differentiate from blood monocytes and infiltrate infected tissue. Following acute infection with hepatotropic viruses, iDCs are essential for re-stimulating virus-specific CD8+ T cells and therefore contribute to virus control. Here we used the lymphocytic choriomeningitis virus (LCMV) model system to identify novel signals, which influence the recruitment and activation of iDCs in the liver. We observed that intrinsic expression of Toso (Faim3, FcμR) influenced the differentiation and activation of iDCs in vivo and DCs in vitro. Lack of iDCs in Toso-deficient (Toso–/–) mice reduced CD8+ T-cell function in the liver and resulted in virus persistence. Furthermore, Toso–/– DCs failed to induce autoimmune diabetes in the rat insulin promoter-glycoprotein (RIP-GP) autoimmune diabetes model. In conclusion, we found that Toso has an essential role in the differentiation and maturation of iDCs, a process that is required for the control of persistence-prone virus infection. PMID:25257173

  10. Toso regulates differentiation and activation of inflammatory dendritic cells during persistence-prone virus infection.

    PubMed

    Lang, P A; Meryk, A; Pandyra, A A; Brenner, D; Brüstle, A; Xu, H C; Merches, K; Lang, F; Khairnar, V; Sharma, P; Funkner, P; Recher, M; Shaabani, N; Duncan, G S; Duhan, V; Homey, B; Ohashi, P S; Häussinger, D; Knolle, P A; Honke, N; Mak, T W; Lang, K S

    2015-01-01

    During virus infection and autoimmune disease, inflammatory dendritic cells (iDCs) differentiate from blood monocytes and infiltrate infected tissue. Following acute infection with hepatotropic viruses, iDCs are essential for re-stimulating virus-specific CD8(+) T cells and therefore contribute to virus control. Here we used the lymphocytic choriomeningitis virus (LCMV) model system to identify novel signals, which influence the recruitment and activation of iDCs in the liver. We observed that intrinsic expression of Toso (Faim3, FcμR) influenced the differentiation and activation of iDCs in vivo and DCs in vitro. Lack of iDCs in Toso-deficient (Toso(-/-)) mice reduced CD8(+) T-cell function in the liver and resulted in virus persistence. Furthermore, Toso(-/-) DCs failed to induce autoimmune diabetes in the rat insulin promoter-glycoprotein (RIP-GP) autoimmune diabetes model. In conclusion, we found that Toso has an essential role in the differentiation and maturation of iDCs, a process that is required for the control of persistence-prone virus infection. PMID:25257173

  11. Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice.

    PubMed

    Frebel, Helge; Nindl, Veronika; Schuepbach, Reto A; Braunschweiler, Thomas; Richter, Kirsten; Vogel, Johannes; Wagner, Carsten A; Loffing-Cueni, Dominique; Kurrer, Michael; Ludewig, Burkhard; Oxenius, Annette

    2012-12-17

    The inhibitory programmed death 1 (PD-1)-programmed death ligand 1 (PD-L1) pathway contributes to the functional down-regulation of T cell responses during persistent systemic and local virus infections. The blockade of PD-1-PD-L1-mediated inhibition is considered as a therapeutic approach to reinvigorate antiviral T cell responses. Yet previous studies reported that PD-L1-deficient mice develop fatal pathology during early systemic lymphocytic choriomeningitis virus (LCMV) infection, suggesting a host protective role of T cell down-regulation. As the exact mechanisms of pathology development remained unclear, we set out to delineate in detail the underlying pathogenesis. Mice deficient in PD-1-PD-L1 signaling or lacking PD-1 signaling in CD8 T cells succumbed to fatal CD8 T cell-mediated immunopathology early after systemic LCMV infection. In the absence of regulation via PD-1, CD8 T cells killed infected vascular endothelial cells via perforin-mediated cytolysis, thereby severely compromising vascular integrity. This resulted in systemic vascular leakage and a consequential collapse of the circulatory system. Our results indicate that the PD-1-PD-L1 pathway protects the vascular system from severe CD8 T cell-mediated damage during early systemic LCMV infection, highlighting a pivotal physiological role of T cell down-regulation and suggesting the potential development of immunopathological side effects when interfering with the PD-1-PD-L1 pathway during systemic virus infections. PMID:23230000

  12. Hepatitis Virus Infections in Poultry.

    PubMed

    Yugo, Danielle M; Hauck, Ruediger; Shivaprasad, H L; Meng, Xiang-Jin

    2016-09-01

    Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis E virus (HEV), duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis virus (THV). While these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. In this article, we aim to review the common and unique features of major poultry hepatitis viruses in an effort to identify the knowledge gaps and aid the prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus B in the family Hepeviridae that naturally infects chickens and consists of three distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly syndrome or big liver and spleen disease in chickens, although the majority of the infected birds are subclinical. Avihepadnaviruses in the family of Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form without clinical signs and rarely progressed to chronicity. The outcome for DHBV infection varies by the host's ability to elicit an immune response and is dose and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B virus (HBV) infections and providing an excellent animal model for human HBV. DHAV is a picornavirus that causes a highly contagious virus infection in ducks with up to 100% flock mortality in ducklings under 6 wk of age, while older birds remain unaffected. The high morbidity and mortality has an economic impact on intensive duck production farming. Duck hepatitis virus Types 2 and 3 are astroviruses in the family of Astroviridae with similarity phylogenetically to turkey astroviruses, implicating the potential for cross-species infections between strains. Duck astrovirus (DAstV) causes

  13. Zika Virus Infection and Zika Fever: Frequently Asked Questions

    MedlinePlus

    ... Updated: 25 March 2016 ABOUT ZIKA What is Zika virus infection? Zika virus infection is caused by the ... possible to characterize the disease better. How is Zika virus transmitted? Zika virus is transmitted to people through ...

  14. Emerging viral infections of the central nervous system: part 1.

    PubMed

    Tyler, Kenneth L

    2009-08-01

    In this 2-part review, I will focus on emerging virus infections of the central nervous system (CNS). Part 1 will introduce the basic features of emerging infections, including their definition, epidemiology, and the frequency of CNS involvement. Important mechanisms of emergence will be reviewed, including viruses spreading into new host ranges as exemplified by West Nile virus (WNV), Japanese encephalitis (JE) virus, Toscana virus, and enterovirus 71 (EV71). Emerging infections also result from opportunistic spread of viruses into known niches, often resulting from attenuated host resistance to infection. This process is exemplified by transplant-associated cases of viral CNS infection caused by WNV, rabies virus, lymphocytic choriomeningitis, and lymphocytic choriomeningitis-like viruses and by the syndrome of human herpesvirus 6 (HHV6)-associated posttransplantation acute limbic encephalitis. The second part of this review begins with a discussion of JC virus and the occurrence of progressive multifocal leukoencephalopathy in association with novel immunomodulatory therapies and then continues with an overview of the risk of infection introduced by imported animals (eg, monkeypox virus) and examples of emerging diseases caused by enhanced competence of viruses for vectors and the spread of vectors (eg, chikungunya virus) and then concludes with examples of novel viruses causing CNS infection as exemplified by Nipah and Hendra viruses and bat lyssaviruses. PMID:19667214

  15. Pathogenesis of Machupo virus infection in primates*

    PubMed Central

    Eddy, G. A.; Scott, S. K.; Wagner, F. S.; Brand, O. M.

    1975-01-01

    Experimental Machupo virus infection of rhesus and cynomolgus monkeys produced a severe illness consisting of an initial clinical phase and a later neurological phase. Cumulative mortality during the two phases was 80% and 95% respectively. Attempts to alter the pathogenesis with decomplementation or immunosuppression resulted in earlier deaths of the monkeys. PMID:182402

  16. The greasy response to virus infections

    PubMed Central

    Tanner, Lukas Bahati; Lee, Benhur

    2013-01-01

    Previews Virus replication requires lipid metabolism, but how lipids mediate virus infection remains obscure. In this issue, Amini-Bavil-Olyaee et al. (2013) reveal that IFITM proteins disturb cholesterol homeostasis to block virus entry. Previously in Cell, Morita and colleagues (2013) showed the antiviral potency of the lipid mediator protectin D1. PMID:23601099

  17. Mental Status after West Nile Virus Infection

    PubMed Central

    Sadek, Joseph; Pergam, Steven; Echevarria, Leonor A.; Davis, Larry E.; Goade, Diane; Harnar, Joanne; Nofchissey, Robert A.; Sewel, C. Mack; Ettestad, Paul

    2006-01-01

    Mental status after acute West Nile virus infection has not been examined objectively. We compared Telephone Interview for Cognitive Status scores of 116 patients with West Nile fever or West Nile neuroinvasive disease. Mental status was poorer and cognitive complaints more frequent with West Nile neuroinvasive disease (p = 0.005). PMID:16965710

  18. Life-Threatening Sochi Virus Infections, Russia.

    PubMed

    Kruger, Detlev H; Tkachenko, Evgeniy A; Morozov, Vyacheslav G; Yunicheva, Yulia V; Pilikova, Olga M; Malkin, Gennadiy; Ishmukhametov, Aydar A; Heinemann, Patrick; Witkowski, Peter T; Klempa, Boris; Dzagurova, Tamara K

    2015-12-01

    Sochi virus was recently identified as a new hantavirus genotype carried by the Black Sea field mouse, Apodemus ponticus. We evaluated 62 patients in Russia with Sochi virus infection. Most clinical cases were severe, and the case-fatality rate was as high as 14.5%. PMID:26584463

  19. Life-Threatening Sochi Virus Infections, Russia

    PubMed Central

    Tkachenko, Evgeniy A.; Morozov, Vyacheslav G.; Yunicheva, Yulia V.; Pilikova, Olga M.; Malkin, Gennadiy; Ishmukhametov, Aydar A.; Heinemann, Patrick; Witkowski, Peter T.; Klempa, Boris; Dzagurova, Tamara K.

    2015-01-01

    Sochi virus was recently identified as a new hantavirus genotype carried by the Black Sea field mouse, Apodemus ponticus. We evaluated 62 patients in Russia with Sochi virus infection. Most clinical cases were severe, and the case-fatality rate was as high as 14.5%. PMID:26584463

  20. Preventing hospitalizations for respiratory syncytial virus infection

    PubMed Central

    Robinson, Joan L; Le Saux, Nicole

    2015-01-01

    Respiratory syncytial virus infection is the leading cause of lower respiratory tract infections in young children. Palivizumab has minimal impact on RSV hospitilization rates as it is only practical to offer it to the highest risk groups. The present statement reviews the published literature and provides updated recommendations regarding palivizumab use in children in Canada. PMID:26435673

  1. CD8+ T cells control Ross River virus infection in musculoskeletal tissues of infected mice.

    PubMed

    Burrack, Kristina S; Montgomery, Stephanie A; Homann, Dirk; Morrison, Thomas E

    2015-01-15

    Ross River virus (RRV), chikungunya virus, and related alphaviruses cause debilitating polyarthralgia and myalgia. Mouse models of RRV and chikungunya virus have demonstrated a role for the adaptive immune response in the control of these infections. However, questions remain regarding the role for T cells in viral control, including the magnitude, location, and dynamics of CD8(+) T cell responses. To address these questions, we generated a recombinant RRV expressing the H-2(b)-restricted glycoprotein 33 (gp33) determinant derived from the glycoprotein of lymphocytic choriomeningitis virus. Using tetramers, we tracked gp33-specific CD8(+) T cells during RRV-lymphocytic choriomeningitis virus infection. We found that acute RRV infection induces activation of CD8(+) T cell responses in lymphoid and musculoskeletal tissues that peak from 10-14 d postinoculation, suggesting that CD8(+) T cells contribute to control of acute RRV infection. Mice genetically deficient for CD8(+) T cells or wild-type mice depleted of CD8(+) T cells had elevated RRV loads in skeletal muscle tissue, but not joint-associated tissues, at 14 d postinoculation, suggesting that the ability of CD8(+) T cells to control RRV infection is tissue dependent. Finally, adoptively transferred T cells were capable of reducing RRV loads in skeletal muscle tissue of Rag1(-/-) mice, indicating that T cells can contribute to the control of RRV infection in the absence of B cells and Ab. Collectively, these data demonstrate a role for T cells in the control of RRV infection and suggest that the antiviral capacity of T cells is controlled in a tissue-specific manner. PMID:25488988

  2. Interferon-γ Inhibits Ebola Virus Infection

    PubMed Central

    Rhein, Bethany A.; Powers, Linda S.; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K.; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A.

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks. PMID:26562011

  3. Interferon-γ Inhibits Ebola Virus Infection.

    PubMed

    Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks. PMID:26562011

  4. Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice

    PubMed Central

    Frebel, Helge; Nindl, Veronika; Schuepbach, Reto A.; Braunschweiler, Thomas; Richter, Kirsten; Vogel, Johannes; Wagner, Carsten A.; Loffing-Cueni, Dominique; Kurrer, Michael; Ludewig, Burkhard

    2012-01-01

    The inhibitory programmed death 1 (PD-1)–programmed death ligand 1 (PD-L1) pathway contributes to the functional down-regulation of T cell responses during persistent systemic and local virus infections. The blockade of PD-1–PD-L1–mediated inhibition is considered as a therapeutic approach to reinvigorate antiviral T cell responses. Yet previous studies reported that PD-L1–deficient mice develop fatal pathology during early systemic lymphocytic choriomeningitis virus (LCMV) infection, suggesting a host protective role of T cell down-regulation. As the exact mechanisms of pathology development remained unclear, we set out to delineate in detail the underlying pathogenesis. Mice deficient in PD-1–PD-L1 signaling or lacking PD-1 signaling in CD8 T cells succumbed to fatal CD8 T cell–mediated immunopathology early after systemic LCMV infection. In the absence of regulation via PD-1, CD8 T cells killed infected vascular endothelial cells via perforin-mediated cytolysis, thereby severely compromising vascular integrity. This resulted in systemic vascular leakage and a consequential collapse of the circulatory system. Our results indicate that the PD-1–PD-L1 pathway protects the vascular system from severe CD8 T cell–mediated damage during early systemic LCMV infection, highlighting a pivotal physiological role of T cell down-regulation and suggesting the potential development of immunopathological side effects when interfering with the PD-1–PD-L1 pathway during systemic virus infections. PMID:23230000

  5. 21 CFR 866.3360 - Lymphocytic choriomeningitis virus serological reagents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lymphocytic choriomeningitis virus serological reagents. 866.3360 Section 866.3360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological...

  6. 21 CFR 866.3360 - Lymphocytic choriomeningitis virus serological reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lymphocytic choriomeningitis virus serological reagents. 866.3360 Section 866.3360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological...

  7. 21 CFR 866.3360 - Lymphocytic choriomeningitis virus serological reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lymphocytic choriomeningitis virus serological reagents. 866.3360 Section 866.3360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological...

  8. 21 CFR 866.3360 - Lymphocytic choriomeningitis virus serological reagents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lymphocytic choriomeningitis virus serological reagents. 866.3360 Section 866.3360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological...

  9. 21 CFR 866.3360 - Lymphocytic choriomeningitis virus serological reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lymphocytic choriomeningitis virus serological reagents. 866.3360 Section 866.3360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological...

  10. METHODS USED TO STUDY RESPIRATORY VIRUS INFECTION

    PubMed Central

    Flaño, Emilio; Jewell, Nancy A.; Durbin, Russell K.; Durbin, Joan E.

    2009-01-01

    This unit describes protocols for infecting the mouse respiratory tract, and assaying virus replication and host response in the lung. Respiratory infections are the leading cause of acute illness worldwide, affecting mostly infants and children in developing countries. The purpose of this unit is to provide the readers with a basic strategy and protocols to study the pathogenesis and immunology of respiratory virus infection using the mouse as an animal model. The procedures include: (i) basic techniques for mouse infection, tissue sampling and preservation, (ii) determination of viral titers, isolation and analysis of lymphocytes and dendritic cells using flow-cytometry, and (iii) lung histology, immunohistochemistry and in situ hybridization. PMID:19499505

  11. Update on oral herpes virus infections.

    PubMed

    Balasubramaniam, Ramesh; Kuperstein, Arthur S; Stoopler, Eric T

    2014-04-01

    Oral herpes virus infections (OHVIs) are among the most common mucosal disorders encountered by oral health care providers. These infections can affect individuals at any age, from infants to the elderly, and may cause significant pain and dysfunction. Immunosuppressed patients may be at increased risk for serious and potential life-threatening complications caused by OHVIs. Clinicians may have difficulty in diagnosing these infections because they can mimic other conditions of the oral mucosa. This article provides oral health care providers with clinically relevant information regarding etiopathogenesis, diagnosis, and management of OHVIs. PMID:24655522

  12. Cells in Dengue Virus Infection In Vivo

    PubMed Central

    Noisakran, Sansanee; Onlamoon, Nattawat; Songprakhon, Pucharee; Hsiao, Hui-Mien; Chokephaibulkit, Kulkanya; Perng, Guey Chuen

    2010-01-01

    Dengue has been recognized as one of the most important vector-borne emerging infectious diseases globally. Though dengue normally causes a self-limiting infection, some patients may develop a life-threatening illness, dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). The reason why DHF/DSS occurs in certain individuals is unclear. Studies in the endemic regions suggest that the preexisting antibodies are a risk factor for DHF/DSS. Viremia and thrombocytopenia are the key clinical features of dengue virus infection in patients. The amounts of virus circulating in patients are highly correlated with severe dengue disease, DHF/DSS. Also, the disturbance, mainly a transient depression, of hematological cells is a critical clinical finding in acute dengue patients. However, the cells responsible for the dengue viremia are unresolved in spite of the intensive efforts been made. Dengue virus appears to replicate and proliferate in many adapted cell lines, but these in vitro properties are extremely difficult to be reproduced in primary cells or in vivo. This paper summarizes reports on the permissive cells in vitro and in vivo and suggests a hematological cell lineage for dengue virus infection in vivo, with the hope that a new focus will shed light on further understanding of the complexities of dengue disease. PMID:22331984

  13. Virus infection, antiviral immunity, and autoimmunity

    PubMed Central

    Getts, Daniel R.; Chastain, Emily M. L.; Terry, Rachael L.; Miller, Stephen D.

    2014-01-01

    Summary As a group of disorders, autoimmunity ranks as the third most prevalent cause of morbidity and mortality in the Western World. However, the etiology of most autoimmune diseases remains unknown. Although genetic linkage studies support a critical underlying role for genetics, the geographic distribution of these disorders as well as the low concordance rates in monozygotic twins suggest that a combination of other factors including environmental ones are involved. Virus infection is a primary factor that has been implicated in the initiation of autoimmune disease. Infection triggers a robust and usually well-coordinated immune response that is critical for viral clearance. However, in some instances, immune regulatory mechanisms may falter, culminating in the breakdown of self-tolerance, resulting in immune-mediated attack directed against both viral and self-antigens. Traditionally, cross-reactive T-cell recognition, known as molecular mimicry, as well as bystander T-cell activation, culminating in epitope spreading, have been the predominant mechanisms elucidated through which infection may culminate in an T-cell-mediated autoimmune response. However, other hypotheses including virus-induced decoy of the immune system also warrant discussion in regard to their potential for triggering autoimmunity. In this review, we discuss the mechanisms by which virus infection and antiviral immunity contribute to the development of autoimmunity. PMID:23947356

  14. Zika Virus Infection Acquired During Brief Travel to Indonesia

    PubMed Central

    Kwong, Jason C.; Druce, Julian D.; Leder, Karin

    2013-01-01

    Zika virus infection closely resembles dengue fever. It is possible that many cases are misdiagnosed or missed. We report a case of Zika virus infection in an Australian traveler who returned from Indonesia with fever and rash. Further case identification is required to determine the evolving epidemiology of this disease. PMID:23878182

  15. Vaccinia virus infections in martial arts gym, Maryland, USA, 2008.

    PubMed

    Hughes, Christine M; Blythe, David; Li, Yu; Reddy, Ramani; Jordan, Carol; Edwards, Cindy; Adams, Celia; Conners, Holly; Rasa, Catherine; Wilby, Sue; Russell, Jamaal; Russo, Kelly S; Somsel, Patricia; Wiedbrauk, Danny L; Dougherty, Cindy; Allen, Christopher; Frace, Mike; Emerson, Ginny; Olson, Victoria A; Smith, Scott K; Braden, Zachary; Abel, Jason; Davidson, Whitni; Reynolds, Mary; Damon, Inger K

    2011-04-01

    Vaccinia virus is an orthopoxvirus used in the live vaccine against smallpox. Vaccinia virus infections can be transmissible and can cause severe complications in those with weakened immune systems. We report on a cluster of 4 cases of vaccinia virus infection in Maryland, USA, likely acquired at a martial arts gym. PMID:21470473

  16. Effects of Aging on Influenza Virus Infection Dynamics

    PubMed Central

    Hernandez-Vargas, Esteban A.; Wilk, Esther; Canini, Laetitia; Toapanta, Franklin R.; Binder, Sebastian C.; Uvarovskii, Alexey; Ross, Ted M.; Guzmán, Carlos A.

    2014-01-01

    ABSTRACT The consequences of influenza virus infection are generally more severe in individuals over 65 years of age (the elderly). Immunosenescence enhances the susceptibility to viral infections and renders vaccination less effective. Understanding age-related changes in the immune system is crucial in order to design prophylactic and immunomodulatory strategies to reduce morbidity and mortality in the elderly. Here, we propose different mathematical models to provide a quantitative understanding of the immune strategies in the course of influenza virus infection using experimental data from young and aged mice. Simulation results suggested a central role of CD8+ T cells for adequate viral clearance kinetics in young and aged mice. Adding the removal of infected cells by natural killer cells did not improve the model fit in either young or aged animals. We separately examined the infection-resistant state of cells promoted by the cytokines alpha/beta interferon (IFN-α/β), IFN-γ, and tumor necrosis factor alpha (TNF-α). The combination of activated CD8+ T cells with any of the cytokines provided the best fits in young and aged animals. During the first 3 days after infection, the basic reproductive number for aged mice was 1.5-fold lower than that for young mice (P < 0.05). IMPORTANCE The fits of our models to the experimental data suggest that the increased levels of IFN-α/β, IFN-γ, and TNF-α (the “inflammaging” state) promote slower viral growth in aged mice, which consequently limits the stimulation of immune cells and contributes to the reported impaired responses in the elderly. A quantitative understanding of influenza virus pathogenesis and its shift in the elderly is the key contribution of this work. PMID:24478442

  17. [A NEW PANDEMIC: ZIKA VIRUS INFECTION].

    PubMed

    Bourée, Patrice

    2016-06-01

    Zika virus is a flavivirus isolated in non human primates in 1647, then in humans 1954 (Uganda). It emerged on Micronesia (island af Yap) in 2007, then in French Polynesia in 2013-2014, in South America (mostly in Brazil and Colombia) in 2015 and in French West Indies in 2016. It is transmitted by the bite of Aedes mosquitoes. Zika virus infection is symptomatic in only 20% of cases and clinical presentation is associated with mild illness. But several neurological complications are reported (as Guillain-Barré syndrome: 48 cases in French Polynesia) and congenital malformations (microcephaly). Laboratory diagnosis is based on virus isolation by PCR. There is no specific treatment or vaccine available against the Zika virs. Prevention is based on measures of protection from mosquitoes bites. PMID:27538321

  18. The immune response to Nipah virus infection.

    PubMed

    Prescott, Joseph; de Wit, Emmie; Feldmann, Heinz; Munster, Vincent J

    2012-09-01

    Nipah virus has recently emerged as a zoonotic agent that is highly pathogenic in humans. Outbreaks have occurred regularly over the last two decades in South and Southeast Asia, where mortality rates reach as high as 100 %. The natural reservoir of Nipah virus has been identified as bats from the Pteropus family, where infection is largely asymptomatic. Human disease is characterized by both respiratory and encephalitic components, and thus far, no effective vaccine or intervention strategies are available. Little is know about how the immune response of either the reservoir host or incidental hosts responds to infection, and how this immune response is either inadequate or might contribute to disease in the dead-end host. Experimental vaccines strategies have given us some insight into the immunological requirements for protection. This review summarizes our current understanding of the immune response to Nipah virus infection and emphasizes the need for further research. PMID:22669317

  19. [Laboratory diagnosis of hepatitis C virus infection].

    PubMed

    Huber, K R; Kittl, E; Sebesta, C; Bauer, K

    2000-01-01

    In Austria, the prevalence of hepatitis C virus infections is 0.7% (17). Exclusion of a putative infection as well as diagnosis and continuous monitoring of HCV-disease produce considerable costs for the health system. How many and which patients with HCV infection will acquire life-threatening complications is by far not clear. Also, the causes for viral persistence and liver-complications remain obscure. For certain, complex interactions of viral and immunological mechanisms will determine the individual outcome of the disease (1). These considerations pose decisive demands on clinical diagnostics for HCV infections to be dealt with in detail: methods for qualitative detection of an infection as well as for analysis of subtypes and for quantitative determination of viral copies; monitoring of therapy; estimation of the progress of the disease and/or efficacy of therapy. PMID:11205177

  20. Systems analysis of West Nile virus infection.

    PubMed

    Suthar, Mehul S; Pulendran, Bali

    2014-06-01

    Emerging and re-emerging mosquito-borne viruses continue to pose a significant threat to human health throughout the world. Over the past decade, West Nile virus (WNV), Dengue virus (DENV), and Chikungunya virus (CHIKV), have caused annual epidemics of virus-induced encephalitis, hemorrhagic fever\\shock syndromes, and arthritis, respectively. Currently, no specific antiviral therapies or vaccines exist for use in humans to combat or prevent these viral infections. Thus, there is a pressing need to define the virus-host interactions that govern immunity and infection outcome. Recent technological breakthroughs in 'omics' resources and high-throughput based assays are beginning to accelerate antiviral drug discovery and improve on current strategies for vaccine design. In this review, we highlight studies with WNV and discuss how traditional and systems biological approaches are being used to rapidly identify novel host targets for therapeutic intervention and develop a deeper conceptual understanding of the host response to virus infection. PMID:24851811

  1. Human papilloma virus infection and psoriasis: Did human papilloma virus infection trigger psoriasis?

    PubMed Central

    Jain, Sonia P.; Gulhane, Sachin; Pandey, Neha; Bisne, Esha

    2015-01-01

    Psoriasis is an autoimmune chronic inflammatory skin disease known to be triggered by streptococcal and HIV infections. However, human papilloma virus infection (HPV) as a triggering factor for the development of psoriasis has not been reported yet. We, hereby report a case of plaque type with inverse psoriasis which probably could have been triggered by genital warts (HPV infection) and discuss the possible pathomechanisms for their coexistence and its management. PMID:26692619

  2. Cardiac involvement in dengue virus infections during the 2004/2005 dengue fever season in Sri Lanka.

    PubMed

    Wichmann, Dominic; Kularatne, Senanayake; Ehrhardt, Stephan; Wijesinghe, Sriyal; Brattig, Norbert W; Abel, Walter; Burchard, Gerd D

    2009-07-01

    Sri Lanka experienced a dramatic increase in dengue cases (15,400) in the 2004 - 2005 season. We carried out a prospective study to investigate cardiac involvement in dengue virus infected patients during the 2004 - 2005 season in Peradeniya, Central Province, Sri Lanka. Cardiac involvement was defined as elevated levels of myoglobin, creatine kinase-muscle brain-type, N-terminal pro-brain natriuretic peptide, heart-type fatty acid-binding protein and troponin T. Twenty-five percent of dengue virus infected patients had one or more of the above tests with abnormal results. PMID:19842405

  3. Double-Stranded RNA Is Detected by Immunofluorescence Analysis in RNA and DNA Virus Infections, Including Those by Negative-Stranded RNA Viruses

    PubMed Central

    Son, Kyung-No; Liang, Zhiguo

    2015-01-01

    ABSTRACT Early biochemical studies of viral replication suggested that most viruses produce double-stranded RNA (dsRNA), which is essential for the induction of the host immune response. However, it was reported in 2006 that dsRNA could be detected by immunofluorescence antibody staining in double-stranded DNA and positive-strand RNA virus infections but not in negative-strand RNA virus infections. Other reports in the literature seemed to support these observations. This suggested that negative-strand RNA viruses produce little, if any, dsRNA or that more efficient viral countermeasures to mask dsRNA are mounted. Because of our interest in the use of dsRNA antibodies for virus discovery, particularly in pathological specimens, we wanted to determine how universal immunostaining for dsRNA might be in animal virus infections. We have detected the in situ formation of dsRNA in cells infected with vesicular stomatitis virus, measles virus, influenza A virus, and Nyamanini virus, which represent viruses from different negative-strand RNA virus families. dsRNA was also detected in cells infected with lymphocytic choriomeningitis virus, an ambisense RNA virus, and minute virus of mice (MVM), a single-stranded DNA (ssDNA) parvovirus, but not hepatitis B virus. Although dsRNA staining was primarily observed in the cytoplasm, it was also seen in the nucleus of cells infected with influenza A virus, Nyamanini virus, and MVM. Thus, it is likely that most animal virus infections produce dsRNA species that can be detected by immunofluorescence staining. The apoptosis induced in several uninfected cell lines failed to upregulate dsRNA formation. IMPORTANCE An effective antiviral host immune response depends on recognition of viral invasion and an intact innate immune system as a first line of defense. Double-stranded RNA (dsRNA) is a viral product essential for the induction of innate immunity, leading to the production of type I interferons (IFNs) and the activation of hundreds

  4. Collapsing glomerulopathy with rare associated coxsackie virus infection: A case report

    PubMed Central

    ZHU, XUEJING; LIU, HONG; YUAN, SHUGUANG; XU, XIANGQING; DONG, ZHEN; LIU, FUYOU

    2016-01-01

    A 38-year-old Chinese man was admitted to the Second Xiangya Hospital of the Central South University (Changsha, China) with heavy proteinuria and rapidly progressing renal failure with nephrotic syndrome. An initial renal biopsy identified collapsing glomerulopathy (CG) with characteristic segmental collapse of the glomerular tuft and marked hypertrophy and hyperplasia of the visceral epithelial cells. A second renal biopsy showed dilation of glomerular capillary loops as a result of effective treatment with rapamycin and anti-viral therapy. Serology for the coxsackie virus antibody was positive when the collapsing lesion was present, and became negative following treatment, which indicated a strong association between the development of CG and coxsackie virus infection. To the best of our knowledge, this is the first case report of CG associated with coxsackie virus infection. PMID:27168819

  5. First Imported Case of Chikungunya Virus Infection in a Travelling Canadian Returning from the Caribbean

    PubMed Central

    Therrien, Christian; Jourdan, Guillaume; Holloway, Kimberly; Tremblay, Cécile; Drebot, Michael A.

    2016-01-01

    This is the first Canadian case of Chikungunya virus (CHIKV) infection reported in a traveller returning from the Caribbean. Following multiple mosquito bites in Martinique Island in January 2014, the patient presented with high fever, headaches, arthralgia on both hands and feet, and a rash on the trunk upon his return to Canada. Initial serological testing for dengue virus infection was negative. Support therapy with nonsteroidal anti-inflammatory drugs was administered. The symptoms gradually improved 4 weeks after onset with residual arthralgia and morning joint stiffness. This clinical feature prompted the clinician to request CHIKV virus serology which was found to be positive for the presence of IgM and neutralizing antibodies. In 2014, over four hundred confirmed CHIKV infection cases were diagnosed in Canadian travellers returning from the Caribbean and Central America. Clinical suspicion of CHIKV or dengue virus infections should be considered in febrile patients with arthralgia returning from the recently CHIKV endemic countries of the Americas. PMID:27366163

  6. Prevalence of Hepatitis Virus Infections in an Institution for Persons with Developmental Disabilities.

    ERIC Educational Resources Information Center

    Woodruff, Bradley A.; Vazquez, Elizabeth

    2002-01-01

    A study involving 1,235 residents of Sonoma Developmental Center found 3 residents had hepatitis C virus infections, and 633 had past or current hepatitis B virus infections. The prevalence of hepatitis B virus infection rose rapidly with longer residence in institutions. Hepatitis A virus infection had occurred in 494 residents. (Contains…

  7. DIESEL EXHAUST ENHANCES INFLUENZA VIRUS INFECTIONS IN RESPIRATORY EPITHELIAL CELLS

    EPA Science Inventory

    Several factors, such as age and nutritional status can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects ...

  8. Respiratory Syncytial Virus Infection (RSV): Transmission and Prevention

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Respiratory Syncytial Virus Infection (RSV) Note: Javascript is disabled or is ... school or childcare. They can then transmit the virus to other members of the family. RSV can ...

  9. Development of vaccines for prevention of Ebola virus infection.

    PubMed

    Ye, Ling; Yang, Chinglai

    2015-02-01

    Ebola virus infection causes severe hemorrhagic fevers with high fatality rates up to 90% in humans, for which no effective treatment is currently available. The ongoing Ebola outbreak in West Africa that has caused over 14,000 human infections and over 5000 deaths underscores its serious threat to the public health. While licensed vaccines against Ebola virus infection are still not available, a number of vaccine approaches have been developed and shown to protect against lethal Ebola virus infection in animal models. This review aims to summarize the advancement of different strategies for Ebola vaccine development with a focus on the discussion of their protective efficacies and possible limitations. In addition, the development of animal models for efficacy evaluation of Ebola vaccines and the mechanism of immune protection against Ebola virus infection are also discussed. PMID:25526819

  10. The neurobiology of varicella zoster virus infection

    PubMed Central

    Gilden, D.; Mahalingam, R.; Nagel, M. A.; Pugazhenthi, S.; Cohrs, R. J.

    2011-01-01

    Varicella zoster virus (VZV) is a neurotropic herpesvirus that infects nearly all humans. Primary infection usually causes chickenpox (varicella), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. Although VZV cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that VZV is latent in ganglia. Declining VZV-specific host immunity decades after primary infection allows virus to reactivate spontaneously, resulting in shingles (zoster) characterized by pain and rash restricted to 1-3 dermatomes. Multiple other serious neurological and ocular disorders also result from VZV reactivation. This review summarizes the current state of knowledge of the clinical and pathological complications of neurological and ocular disease produced by VZV reactivation, molecular aspects of VZV latency, VZV virology and VZV-specific immunity, the role of apoptosis in VZV-induced cell death, and the development of an animal model provided by simian varicella virus infection of monkeys. PMID:21342215

  11. Adolescents and human immunodeficiency virus infection.

    PubMed

    Anderson, J R

    1992-12-01

    As of March 31, 1992, individuals 13 to 19 years of age had been diagnosed with acquired immunodeficiency syndrome; over one third were diagnosed in the past 2 years alone. Because of the long incubation period from initial infection to acquired immunodeficiency syndrome diagnosis, the majority of young adults with acquired immunodeficiency syndrome were probably initially infected as adolescents. In 1991, 34% of adolescents with acquired immunodeficiency syndrome were female, and their predominant mode of transmission was heterosexual contact. Human immunodeficiency virus seroprevalence studies of adolescents show a male-to-female ratio approaching 1:1, with many human immunodeficiency virus-infected adolescent women identifying none of the standard risk. Factors such as sexual and drug experimentation, risk taking, and sense of invulnerability so characteristic of adolescence put adolescents at special risk for human immunodeficiency virus. There is no published information on if or how clinical manifestations of human immunodeficiency virus disease in adolescents might differ from those seen in adults. Medical care should be broad-based and should include access to clinical trials for new drug treatments. General knowledge levels about acquired immunodeficiency syndrome are high among US adolescents, but behavioral changes have lagged behind. All adolescents should be targeted for intensive education about human immunodeficiency virus along with interventions designed to enhance their general coping, communication, and decision-making skills. PMID:1450349

  12. Diversity of Viruses Infecting the Green Microalga Ostreococcus lucimarinus

    PubMed Central

    Derelle, Evelyne; Monier, Adam; Cooke, Richard; Worden, Alexandra Z.

    2015-01-01

    ABSTRACT The functional diversity of eukaryotic viruses infecting a single host strain from seawater samples originating from distant marine locations is unknown. To estimate this diversity, we used lysis plaque assays to detect viruses that infect the widespread species Ostreococcus lucimarinus, which is found in coastal and mesotrophic systems, and O. tauri, which was isolated from coastal and lagoon sites from the northwest Mediterranean Sea. Detection of viral lytic activities against O. tauri was not observed using seawater from most sites, except those close to the area where the host strain was isolated. In contrast, the more cosmopolitan O. lucimarinus species recovered viruses from locations in the Atlantic and Pacific Oceans and the Mediterranean Sea. Six new O. lucimarinus viruses (OlVs) then were characterized and their genomes sequenced. Two subgroups of OlVs were distinguished based on their genetic distances and on the inversion of a central 32-kb-long DNA fragment, but overall their genomes displayed a high level of synteny. The two groups did not correspond to proximity of isolation sites, and the phylogenetic distance between these subgroups was higher than the distances observed among viruses infecting O. tauri. Our study demonstrates that viruses originating from very distant sites are able to infect the same algal host strain and can be more diverse than those infecting different species of the same genus. Finally, distinctive features and evolutionary distances between these different viral subgroups does not appear to be linked to biogeography of the viral isolates. IMPORTANCE Marine eukaryotic phytoplankton virus diversity has yet to be addressed, and more specifically, it is unclear whether diversity is connected to geographical distance and whether differential infection and lysis patterns exist among such viruses that infect the same host strain. Here, we assessed the genetic distance of geographically segregated viruses that infect the

  13. Influenza virus infection, ozone exposure, and fibrogenesis.

    PubMed

    Jakab, G J; Bassett, D J

    1990-05-01

    Oxidant exposure following chemically induced lung injury exacerbates the tendency to develop pulmonary fibrosis. Influenza virus pneumonitis causes severe acute lung damage that, upon resolution, is followed by a persistent alveolitis and parenchymal changes characterized by patchy interstitial pneumonia and collagen deposition in the affected areas. To determine whether oxidant exposure exacerbates the virus-induced alveolitis and residual lung damage, mice were infected by aerosol inhalation with influenza A virus and continuously exposed to 0.5 ppm ozone or ambient air. Noninfected control mice were exposed to either ambient air or ozone. On various days during the first month after infection, groups of mice were sacrificed and their lungs assessed for acute injury (lung lavage albumin, total and differential cell counts, wet/dry ratios, and morphometry). At 30, 60, 90, and 120 days after infection, groups of mice were sacrificed for total and differential lavage cell counts, lung hydroxyproline content, and morphometric analysis. Ozone exposure did not alter the proliferation of virus in the lungs as quantitated by infectious virus titers of lung homogenates at 1, 4, 7, 10, and 15 days after virus infection but mitigated the virus-induced acute lung injury by approximately 50%. After Day 30 a shift in the character of the pulmonary lesions was observed in that continuous exposure to ozone potentiated the postinfluenzal alveolitis and structural changes in the lung parenchyma. Additional studies suggest that the mechanism for the enhanced postinfluenzal lung damage may be related to the oxidant impairing the repair process of the acute influenzal lung damage. These data demonstrate that ozone exposure mitigates acute virus-induced lung injury and potentiates residual lung damage. PMID:2339849

  14. Pathogenesis of human immunodeficiency virus infection.

    PubMed Central

    Levy, J A

    1993-01-01

    The lentivirus human immunodeficiency virus (HIV) causes AIDS by interacting with a large number of different cells in the body and escaping the host immune response against it. HIV is transmitted primarily through blood and genital fluids and to newborn infants from infected mothers. The steps occurring in infection involve an interaction of HIV not only with the CD4 molecule on cells but also with other cellular receptors recently identified. Virus-cell fusion and HIV entry subsequently take place. Following virus infection, a variety of intracellular mechanisms determine the relative expression of viral regulatory and accessory genes leading to productive or latent infection. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; with other cells, such as macrophages, persistent infection can occur, creating reservoirs for the virus in many cells and tissues. HIV strains are highly heterogeneous, and certain biologic and serologic properties determined by specific genetic sequences can be linked to pathogenic pathways and resistance to the immune response. The host reaction against HIV, through neutralizing antibodies and particularly through strong cellular immune responses, can keep the virus suppressed for many years. Long-term survival appears to involve infection with a relatively low-virulence strain that remains sensitive to the immune response, particularly to control by CD8+ cell antiviral activity. Several therapeutic approaches have been attempted, and others are under investigation. Vaccine development has provided some encouraging results, but the observations indicate the major challenge of preventing infection by HIV. Ongoing research is necessary to find a solution to this devastating worldwide epidemic. Images PMID:8464405

  15. First Imported Case of Zika Virus Infection into Korea.

    PubMed

    Jang, Hee-Chang; Park, Wan Beom; Kim, Uh Jin; Chun, June Young; Choi, Su-Jin; Choe, Pyoeng Gyun; Jung, Sook-In; Jee, Youngmee; Kim, Nam-Joong; Choi, Eun Hwa; Oh, Myoung-Don

    2016-07-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil. PMID:27366020

  16. First Imported Case of Zika Virus Infection into Korea

    PubMed Central

    Jee, Youngmee

    2016-01-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil. PMID:27366020

  17. Antibody producing B lineage cells invade the central nervous system predominantly at the time of and triggered by acute Epstein-Barr virus infection: A hypothesis on the origin of intrathecal immunoglobulin synthesis in multiple sclerosis.

    PubMed

    Otto, Carolin; Hofmann, Jörg; Ruprecht, Klemens

    2016-06-01

    Patients with multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), typically have an intrathecal synthesis of immunoglobulin (Ig)G. Intrathecal IgG is produced by B lineage cells that entered the CNS, but why and when these cells invade the CNS of patients with MS is unknown. The intrathecal IgG response in patients with MS is polyspecific and part of it is directed against different common viruses (e.g. measles virus, rubella virus, varicella zoster virus). Strong and consistent evidence suggests an association of MS and Epstein-Barr virus (EBV) infection and EBV seroprevalence in patients with MS is practically 100%. However, intriguingly, despite of the universal EBV seroprevalence, the frequency of intrathecally produced IgG to EBV in patients with MS is much lower than that of intrathecally produced IgG to other common viruses. The acute phase of primary EBV infection is characterized by a strong polyclonal B cell activation. As typical for humoral immune responses against viruses, EBV specific IgG is produced only with a temporal delay after acute EBV infection. Aiming to put the above facts into a logical structure, we here propose the hypothesis that in individuals going on to develop MS antibody producing B lineage cells invade the CNS predominantly at the time of and triggered by acute primary EBV infection. Because at the time of acute EBV infection EBV IgG producing B lineage cells have not yet occurred, the hypothesis could explain the universal EBV seroprevalence and the low frequency of intrathecally produced IgG to EBV in patients with MS. Evidence supporting the hypothesis could be provided by large prospective follow-up studies of individuals with symptomatic primary EBV infection (infectious mononucleosis). Furthermore, the clarification of the molecular mechanism underlying an EBV induced invasion of B lineage cells into the CNS of individuals going on to develop MS could corroborate it, too. If true, our

  18. Analysis of Subcellular Prefoldin 1 Redistribution During Rabies Virus Infection

    PubMed Central

    Zhang, Jinyang; Han, Qinqin; Song, Yuzhu; Chen, Qiang; Xia, Xueshan

    2015-01-01

    Background: Rabies virus (RABV) is one of the old deadly zoonotic viruses. It attacks the central nervous system and causes acute encephalitis in humans and animals. Host factors are known to be essential for virus infection and replication in cells. The identification of the key host factors required for RABV infection may provide important information on RABV replication and may provide new potential targets for RABV drug discovery. Objectives: This study aimed to investigate the change in the subcellular distribution and expression of the host protein Prefoldin subunit 1 (PFDN1) in RABV-infected cells and the viral expression of plasmids in the transfected cells. Materials and Methods: Mouse Neuro-2a (N2a) cells were infected by RABV or transfected with the plasmids of the nucleoprotein (N) and/or phosphoprotein (P) gene of RABV. The subcellular distribution of PFDN1 was analyzed by confocal microscopy, and the transcription levels of PFDN1 in the N and/or P gene of the RABV-transfected or RABV-infected N2a cells were assessed via real-time quantitative polymerase chain reaction. Results: Confocal microscopy showed that PFDN1 was colocalized with the N protein of RABV in the infected N2a cells and was mainly recruited to the characteristic Negri-Body-Like (NBL) structures in the cytoplasm, as well as the cotransfection of the N and P genes of RABV. The transcription of PFDN1 in the RABV-infected N2a cells was upregulated, whereas the transfection of the N and/or P genes did not result in the upregulation of PFDN1. Conclusions: The results of this work demonstrated that the subcellular distribution of PFDN1 was altered in the RABV-infected N2a cells and colocalized with the N protein of RABV in the NBL structures. PMID:26421138

  19. Hepatitis E Virus Infection among Solid Organ Transplant Recipients, the Netherlands

    PubMed Central

    Pas, Suzan D.; de Man, Rob A.; Mulders, Claudia; Balk, Aggie H.M.M.; van Hal, Peter T.W.; Weimar, Willem; Koopmans, Marion P.G.; Osterhaus, Albert D.M.E.

    2012-01-01

    We screened 1,200 living heart, lung, liver, and kidney transplant recipients for hepatitis E virus infection by reverse transcription PCR. In 12 (1%) patients, hepatitis E virus infection was identified; in 11 patients, chronic infection developed. This immunocompromised population is at risk for hepatitis E virus infection. PMID:22516170

  20. KINETIC PROFILE OF INFLUENZA VIRUS INFECTION IN THREE RAT STRAINS

    EPA Science Inventory

    Abstract

    Influenza infection is a respiratory disease of viral origin that can cause major epidemics in man. The influenza virus infects and damages epithelial cells of the respiratory tract and causes pneumonia. Lung lesions of mice infected with influenza virus resembl...

  1. Comparative pathology of select agent influenza A virus infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A virus infections may spread rapidly in human populations and cause acute respiratory disease with variable mortality. Two of these influenza viruses have been designated as select agents because of the high case fatality rate: 1918 H1N1 virus and highly pathogenic avian influenza (HPAI) ...

  2. Susceptibility of mouse macrophage J774 to dengue virus infection.

    PubMed

    Moreno-Altamirano, María M B; Sánchez-García, F Javier; Legorreta-Herrera, Martha; Aguilar-Carmona, Israel

    2007-01-01

    The aim of this study was to investigate whether the J774 mouse macrophage cell line could be used as an in vitro model for dengue virus infection (DENV). After 3 days, infection in J774 cells was assessed by detecting dengue virus non-structural protein 1 (NSP-1) production either by dot blot or indirect immunofluorescence assay (IFA) of saponine-permeabilized J774 cells and then confirmed by RT-PCR (171 bp product, corresponding to the DENV-2 core). Based on the presence of NSP-1 in infected but not in non-infected cells by both IFA and dot blot, as well as the amplification of a 171-bp DENV-2-specific RT-PCR product exclusively in the infected cells, the J774 cell line was found to be permissive for dengue virus infection. As far as we know, this is the first report that the J774 mouse macrophage cell line is infected with dengue virus and, thus, that it can be used as an alternative in vitro model for dengue virus infection studies. This finding could help to further elucidate the mechanisms involved in dengue virus infection and pathogenesis. PMID:17356302

  3. Emerging Viral Infections of the Central Nervous System

    PubMed Central

    Tyler, Kenneth L.

    2010-01-01

    In this 2-part review, I will focus on emerging virus infections of the central nervous system (CNS). Part 1 will introduce the basic features of emerging infections, including their definition, epidemiology, and the frequency of CNS involvement. Important mechanisms of emergence will be reviewed, including viruses spreading into new host ranges as exemplified by West Nile virus (WNV), Japanese encephalitis (JE) virus, Toscana virus, and enterovirus 71 (EV71). Emerging infections also result from opportunistic spread of viruses into known niches, often resulting from attenuated host resistance to infection. This process is exemplified by transplant-associated cases of viral CNS infection caused by WNV, rabies virus, lymphocytic choriomeningitis, and lymphocytic choriomeningitis–like viruses and by the syndrome of human herpesvirus 6 (HHV6)–associated posttransplantation acute limbic encephalitis. The second part of this review begins with a discussion of JC virus and the occurrence of progressive multifocal leukoencephalopathy in association with novel immunomodulatory therapies and then continues with an overview of the risk of infection introduced by imported animals (eg, monkeypox virus) and examples of emerging diseases caused by enhanced competence of viruses for vectors and the spread of vectors (eg, chikungunya virus) and then concludes with examples of novel viruses causing CNS infection as exemplified by Nipah and Hendra viruses and bat lyssaviruses. PMID:19667214

  4. Fatal Case of Polymicrobial Meningitis Caused by Cryptococcus liquefaciens and Mycobacterium tuberculosis Complex in a Human Immunodeficiency Virus-Infected Patient

    PubMed Central

    Rodas-Rodríguez, Lia; Díaz-Paz, Manuel; Palacios-Rivera, Hilda; Firacative, Carolina; Meyer, Wieland; Alcázar-Castillo, Myriam

    2015-01-01

    We describe a fatal case of polymicrobial meningitis in a human immunodeficiency virus-infected patient from Guatemala caused by Cryptococcus liquefaciens and Mycobacterium tuberculosis complex. Central nervous system infections caused concurrently by these species are extremely rare. This is also the first report of disseminated disease caused by C. liquefaciens. PMID:26019205

  5. First case of imported Zika virus infection in Spain.

    PubMed

    Bachiller-Luque, Pablo; Domínguez-Gil González, Marta; Álvarez-Manzanares, Jesús; Vázquez, Ana; De Ory, Fernando; Sánchez-Seco Fariñas, M Paz

    2016-04-01

    We report a case of Zika virus (ZIKV) infection in a patient with diarrhea, fever, synovitis, non-purulent conjunctivitis, and with discreet retro-orbital pain, after returning from Colombia in January 2016. The patient referred several mosquito bites. Presence of ZIKV was detected by PCR (polymerase chain reaction) in plasma. Rapid microbiological diagnosis of ZIKV infection is needed in European countries with circulation of its vector, in order to avoid autochthonous circulation. The recent association of ZIKV infection with abortion and microcephaly, and a Guillain-Barré syndrome highlights the need for laboratory differentiation of ZIKV from other virus infection. Women with potential risk for Zika virus infection who are pregnant or planning to become pregnant must mention that fact during prenatal visits in order to be evaluated and properly monitored. PMID:26994814

  6. Interferon-inducible GTPase: a novel viral response protein involved in rabies virus infection.

    PubMed

    Li, Ling; Wang, Hualei; Jin, Hongli; Cao, Zengguo; Feng, Na; Zhao, Yongkun; Zheng, Xuexing; Wang, Jianzhong; Li, Qian; Zhao, Guoxing; Yan, Feihu; Wang, Lina; Wang, Tiecheng; Gao, Yuwei; Tu, Changchun; Yang, Songtao; Xia, Xianzhu

    2016-05-01

    Rabies virus infection is a major public health concern because of its wide host-interference spectrum and nearly 100 % lethality. However, the interactions between host and virus remain unclear. To decipher the authentic response in the central nervous system after rabies virus infection, a dynamic analysis of brain proteome alteration was performed. In this study, 104 significantly differentially expressed proteins were identified, and intermediate filament, interferon-inducible GTPases, and leucine-rich repeat-containing protein 16C were the three outstanding groups among these proteins. Interferon-inducible GTPases were prominent because of their strong upregulation. Moreover, quantitative real-time PCR showed distinct upregulation of interferon-inducible GTPases at the level of transcription. Several studies have shown that interferon-inducible GTPases are involved in many biological processes, such as viral infection, endoplasmic reticulum stress response, and autophagy. These findings indicate that interferon-inducible GTPases are likely to be a potential target involved in rabies pathogenesis or the antiviral process. PMID:26906695

  7. [Lopinavir/ritonavir in human immunodeficiency virus-infected women].

    PubMed

    Téllez, María Jesús

    2014-11-01

    There are clear sex-related biological differences between men and women. Diseases that affect the two sexes differently are studied separately. However, some diseases affect both men and women, but their incidence or outcome are clearly different. In human immunodeficiency virus infection, the potential differences in the effects of antiretroviral therapy are poorly characterized and few studies have been designed to elucidate these differences. Moreover, women are usually poorly represented in clinical trials of antiretroviral drugs. PMID:25542872

  8. Neurological Complications of Ebola Virus Infection.

    PubMed

    Billioux, Bridgette Jeanne; Smith, Bryan; Nath, Avindra

    2016-07-01

    Ebola virus disease is one of the deadliest pathogens known to man, with a mortality rate between 25-90% depending on the species and outbreak of Ebola. Typically, it presents with fever, headache, voluminous vomiting and diarrhea, and can progress to a hemorrhagic illness; neurologic symptoms, including meningoencephalitis, seizures, and coma, can also occur. Recently, an outbreak occurred in West Africa, affecting > 28,000 people, and killing > 11,000. Owing to the magnitude of this outbreak, and the large number (>17,000) of Ebola survivors, the medical and scientific communities are learning much more about the acute manifestations and sequelae of Ebola. A number of neurologic complications can occur after Ebola, such as seizures, memory loss, headaches, cranial nerve abnormalities, and tremor. Ebola may also persist in some immunologically privileged sites, including the central nervous system, and can rarely lead to relapse in disease. Owing to these findings, it is important that survivors are evaluated and monitored for neurologic symptoms. Much is unknown about this disease, and treatment remains largely supportive; however, with ongoing clinical and basic science, the mechanisms of how Ebola affects the central nervous system and how it persists after acute disease will hopefully become more clear, and better treatments and clinical practices for Ebola patients will be developed. PMID:27412684

  9. Protective effect of dietary xylitol on influenza A virus infection.

    PubMed

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

  10. Role of oxidative stress in rabies virus infection.

    PubMed

    Jackson, Alan C; Kammouni, Wafa; Fernyhough, Paul

    2011-01-01

    Recent studies in an experimental model of rabies indicated that there are major structural changes in the brain involving neuronal processes that are associated with severe clinical disease. Cultured adult mouse dorsal root ganglion (DRG) neurons are a good in vitro model for studying the mechanisms involved in rabies virus-induced degeneration of neurites (axons) because, unlike other neuronal cell types, these neurons are fairly permissive to rabies virus infection. DRG neurons infected with the challenge virus standard-11 (CVS) strain of rabies virus show axonal swellings and immunostaining for 4-hydroxy-2-nonenal (4-HNE), indicating evidence of lipid peroxidation associated with oxidative stress, and also reduced axonal growth in comparison with mock-infected DRG neurons. Treatment with the antioxidant N-acetyl cysteine prevented the reduction in axonal outgrowth that occurred with CVS infection. The axonal swellings with 4-HNE-labeled puncta were found to be associated with aggregations of actively respiring mitochondria. We postulate that rabies virus infection likely induces mitochondrial dysfunction resulting in oxidative stress and degenerative changes involving neuronal processes. This mitochondrial dysfunction may be the result of either direct or indirect effects of the virus on the mitochondrial electron-transport chain or it may occur through other mechanisms. Further investigations are needed to gain a better understanding of the basic mechanisms involved in the oxidative damage associated with rabies virus infection. This information may prove helpful in the design of future therapeutic effects for this dreaded ancient disease. PMID:21601046

  11. Potent neutralizing monoclonal antibodies against Ebola virus infection.

    PubMed

    Zhang, Qi; Gui, Miao; Niu, Xuefeng; He, Shihua; Wang, Ruoke; Feng, Yupeng; Kroeker, Andrea; Zuo, Yanan; Wang, Hua; Wang, Ying; Li, Jiade; Li, Chufang; Shi, Yi; Shi, Xuanling; Gao, George F; Xiang, Ye; Qiu, Xiangguo; Chen, Ling; Zhang, Linqi

    2016-01-01

    Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection. PMID:27181584

  12. Epidemiological and Virological Characterization of Influenza B Virus Infections.

    PubMed

    Sharabi, Sivan; Drori, Yaron; Micheli, Michal; Friedman, Nehemya; Orzitzer, Sara; Bassal, Ravit; Glatman-Freedman, Aharona; Shohat, Tamar; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

    2016-01-01

    While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011-2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections. PMID:27533045

  13. Potent neutralizing monoclonal antibodies against Ebola virus infection

    PubMed Central

    Zhang, Qi; Gui, Miao; Niu, Xuefeng; He, Shihua; Wang, Ruoke; Feng, Yupeng; Kroeker, Andrea; Zuo, Yanan; Wang, Hua; Wang, Ying; Li, Jiade; Li, Chufang; Shi, Yi; Shi, Xuanling; Gao, George F.; Xiang, Ye; Qiu, Xiangguo; Chen, Ling; Zhang, Linqi

    2016-01-01

    Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection. PMID:27181584

  14. Protective Effect of Dietary Xylitol on Influenza A Virus Infection

    PubMed Central

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

  15. Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection

    PubMed Central

    Ozden, Simona; Huerre, Michel; Riviere, Jean-Pierre; Coffey, Lark L.; Afonso, Philippe V.; Mouly, Vincent; de Monredon, Jean; Roger, Jean-Christophe; El Amrani, Mohamed; Yvin, Jean-Luc; Jaffar, Marie-Christine; Frenkiel, Marie-Pascale; Sourisseau, Marion; Schwartz, Olivier; Butler-Browne, Gillian; Desprès, Philippe; Gessain, Antoine; Ceccaldi, Pierre-Emmanuel

    2007-01-01

    Background Chikungunya (CHIK) virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK virus was associated with an unprecedented magnitude outbreak of CHIK disease in the Indian Ocean. Clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. Since the cellular targets of CHIK virus in humans are unknown, we studied the pathogenic events and targets of CHIK infection in skeletal muscle. Methodology/Principal Findings Immunohistology on muscle biopsies from two CHIK virus-infected patients with myositic syndrome showed that viral antigens were found exclusively inside skeletal muscle progenitor cells (designed as satelllite cells), and not in muscle fibers. To evaluate the ability of CHIK virus to replicate in human satellite cells, we assessed virus infection on primary human muscle cells; viral growth was observed in CHIK virus-infected satellite cells with a cytopathic effect, whereas myotubes were essentially refractory to infection. Conclusions/Significance This report provides new insights into CHIK virus pathogenesis, since it is the first to identify a cellular target of CHIK virus in humans and to report a selective infection of muscle satellite cells by a viral agent in humans. PMID:17565380

  16. The Aedes aegypti Toll Pathway Controls Dengue Virus Infection

    PubMed Central

    Xi, Zhiyong; Ramirez, Jose L.; Dimopoulos, George

    2008-01-01

    Aedes aegypti, the mosquito vector of dengue viruses, utilizes its innate immune system to ward off a variety of pathogens, some of which can cause disease in humans. To date, the features of insects' innate immune defenses against viruses have mainly been studied in the fruit fly Drosophila melanogaster, which appears to utilize different immune pathways against different types of viruses, in addition to an RNA interference–based defense system. We have used the recently released whole-genome sequence of the Ae. aegypti mosquito, in combination with high-throughput gene expression and RNA interference (RNAi)-based reverse genetic analyses, to characterize its response to dengue virus infection in different body compartments. We have further addressed the impact of the mosquito's endogenous microbial flora on virus infection. Our findings indicate a significant role for the Toll pathway in regulating resistance to dengue virus, as indicated by an infection-responsive regulation and functional assessment of several Toll pathway–associated genes. We have also shown that the mosquito's natural microbiota play a role in modulating the dengue virus infection, possibly through basal-level stimulation of the Toll immune pathway. PMID:18604274

  17. Epidemiological and Virological Characterization of Influenza B Virus Infections

    PubMed Central

    Sharabi, Sivan; Drori, Yaron; Micheli, Michal; Friedman, Nehemya; Orzitzer, Sara; Bassal, Ravit; Glatman-Freedman, Aharona; Shohat, Tamar; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

    2016-01-01

    While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011–2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections. PMID:27533045

  18. [Dementia and human inmmunodeficiency virus infection].

    PubMed

    Gray, F

    1998-01-01

    HIV-associated neurological manifestations: dementia, myelopathy, and neuropathy, have become one of the commonest causes of neurological disorders in young people. Cognitive impairment develops in about 30 p. 100 of patients with AIDS and frank dementia in 15 to 20 p. 100 with an annual incidence after AIDS of approximatively 7 p. 100. Typically, the onset of dementia is relatively abrupt over a few weeks or months. The clinical manifestations of the encephalopathy now termed "HIV-dementia", suggest predominant subcortical or frontal involvement. Typical presentation includes apathy and inertia, memory loss and cognitive slowing, minor depressive symptoms and withdrawal from usual activities. Neurological examination may show hypertonia of lower limbs, tremor, clonus, frontal release signs and hyperactive reflexes. Terminally, the patient is bedbound, incontinent, abulic or mute with decorticate posturing leading to death over 3 to 6 months. However, a stabilisation and even a regression of the cognitive disorders have been observed following antiretroviral treatment. Radiological features of HIV dementia include both central and cortical atrophy and white matter rarefaction. However they are neither invariable nor specific. Together with CSF examination, they are more important to exclude opportunistic infections. Indeed, although a completely normal CSF profile may reasonably exclude the diagnosis; at present, no single test or combination of tests can reliably diagnose HIV dementia. Although the clinical characteristics of HIV-dementia are now clearly established, its pathogenesis is unclear and its pathological counterpart remains a matter of debate. A number of "HIV-induced" lesions may be found in the brain of AIDS patients and their causative role in HIV-dementia has been considered. They include HIV encephalitis due to productive CNS infection by the virus, diffuse white matter pallor "HIV-leukoencephalopathy" reflecting an abnormality of the blood brain

  19. Chemokine gene expression in the brains of mice with lymphocytic choriomeningitis.

    PubMed Central

    Asensio, V C; Campbell, I L

    1997-01-01

    Chemokines are pivotal in the trafficking of leukocytes. In the present study, we examined the expression of multiple chemokine genes during the course of lymphocytic choriomeningitis (LCM) in mice. In noninfected mice, no detectable chemokine gene expression was found in the brain; however, by day 3 postinfection, the induction of a number of chemokine mRNAs was observed as follows (in order from the greatest to the least): cytokine responsive gene-2 or interferon-inducible 10-kDa protein (Crg-2/IP-10), RANTES, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 (MIP-1beta), and MCP-3. At day 6 postinfection, the expression of these chemokine mRNAs was increased, and low expression of lymphotactin, C10, MIP-2, and MIP-1alpha mRNAs was detectable. Transcript for T-cell activation-3 was not detectable in the brain at any time following LCM virus (LCMV) infection. With some exceptions, a pattern of chemokine gene expression similar to that in the brain was observed in the peripheral organs of LCMV-infected mice. Mice that lacked expression of gamma interferon developed LCM and had a qualitatively similar but quantitatively reduced cerebral chemokine gene expression profile. In contrast, little or no chemokine gene expression was detectable in the brains of LCMV-infected athymic mice which did not develop LCM. Expression of Crg-2/IP-10 RNA was localized to predominantly resident cells of the central nervous system (CNS) and overlapped with sites of viral infection and immune cell infiltration. These findings demonstrate the expression of a number of chemokine genes in the brains of mice infected with LCMV. The pattern of chemokine gene expression in LCM may profoundly influence the characteristic phenotype and response of leukocytes in the brain and contribute to the immunopathogenesis of this fatal CNS infection. PMID:9311871

  20. Recurrent Transcortical Motor Aphasia-Another CNS Infectious Syndrome Associated with Herpes Virus Infection.

    PubMed

    Govindarajan, Raghav; Salgado, Efrain

    2016-01-01

    Herpes simplex encephalitis is an acute/subacute illness that causes both general and focal signs of cerebral dysfunction with fever, headache, and confusion as cardinal features. Recurrent herpes simplex meningitis, also known as Mollaret's meningitis, is another manifestation of central nervous system herpetic infection with recurrent episodes of fever, headache, and nuchal rigidity associated with cerebrospinal fluid (CSF) evidence of active herpes simplex infection. Bell's palsy is yet another manifestation of a herpes virus infection in at least some reported cases documented by CSF analysis. We report a case of a 70-year-old male who presented with acute transcortical motor aphasia initiating a stroke work-up that was negative. Physical examination revealed genital vesicles, and the CSF was consistent with active herpes simplex infection. PMID:26958155

  1. T Follicular Helper Cell-Dependent Clearance of a Persistent Virus Infection Requires T Cell Expression of the Histone Demethylase UTX.

    PubMed

    Cook, Kevin D; Shpargel, Karl B; Starmer, Joshua; Whitfield-Larry, Fatima; Conley, Bridget; Allard, Denise E; Rager, Julia E; Fry, Rebecca C; Davenport, Marsha L; Magnuson, Terry; Whitmire, Jason K; Su, Maureen A

    2015-10-20

    Epigenetic changes, including histone methylation, control T cell differentiation and memory formation, though the enzymes that mediate these processes are not clear. We show that UTX, a histone H3 lysine 27 (H3K27) demethylase, supports T follicular helper (Tfh) cell responses that are essential for B cell antibody generation and the resolution of chronic viral infections. Mice with a T cell-specific UTX deletion had fewer Tfh cells, reduced germinal center responses, lacked virus-specific immunoglobulin G (IgG), and were unable to resolve chronic lymphocytic choriomeningitis virus infections. UTX-deficient T cells showed decreased expression of interleukin-6 receptor-α and other Tfh cell-related genes that were associated with increased H3K27 methylation. Additionally, Turner Syndrome subjects, who are predisposed to chronic ear infections, had reduced UTX expression in immune cells and decreased circulating CD4(+) CXCR5(+) T cell frequency. Thus, we identify a critical link between UTX in T cells and immunity to infection. PMID:26431949

  2. Virus infection-associated bone marrow B cell depletion and impairment of humoral immunity to heterologous infection mediated by TNF-alpha/LTalpha.

    PubMed

    Borrow, Persephone; Hou, Sam; Gloster, Simone; Ashton, Miranda; Hyland, Lisa

    2005-02-01

    We previously showed that influenza virus infection of mice induces a depletion of bone marrow B lineage cells due to apoptosis of early B cells mediated by a mechanism involving TNF-alpha/LTalpha. Here we demonstrate that this effect is also observed with acute lymphocytic choriomeningitis virus (LCMV) infection and resulted in a deficiency of both splenic transitional B cells and mature follicular B cells. To determine whether there was an associated impairment of humoral immunity, we infected mice with LCMV and 10 days later at the peak of the B cell depletion, inoculated them with influenza virus. We found that influenza virus-specific antibody titers were dramatically reduced in mice recovering from LCMV infection compared to those in mice infected with influenza virus alone. Further, we showed that there was no reduction of the influenza virus-specific antibody response in LCMV-infected TNF-alpha/LTalpha-deficient mice, suggesting that TNF-alpha/LTalpha-mediated effects on bone marrow and/or peripheral lymphocytes were responsible for the observed impairment in humoral immunity. These results show that the TNF-alpha/LTalpha production induced following infection with diverse viruses has detrimental effects on early B cells in the bone marrow, and may be among the factors that lead to the severely compromised humoral immunity observed to subsequent heterologous infections. PMID:15657949

  3. Trace-Forward Investigation of Mice in Response to Lymphocytic Choriomeningitis Virus Outbreak

    PubMed Central

    Knust, Barbara; Petersen, Bret; Gabel, Julie; Manning, Craig; Drenzek, Cherie; Ströher, Ute; Rollin, Pierre E.; Thoroughman, Douglas; Nichol, Stuart T.

    2014-01-01

    During follow-up of a 2012 US outbreak of lymphocytic choriomeningitis virus (LCMV), we conducted a trace-forward investigation. LCMV-infected feeder mice originating from a US rodent breeding facility had been distributed to >500 locations in 21 states. All mice from the facility were euthanized, and no additional persons tested positive for LCMV infection. PMID:24447898

  4. A conservation law for virus infection kinetics in vitro.

    PubMed

    Kakizoe, Yusuke; Morita, Satoru; Nakaoka, Shinji; Takeuchi, Yasuhiro; Sato, Kei; Miura, Tomoyuki; Beauchemin, Catherine A A; Iwami, Shingo

    2015-07-01

    Conservation laws are among the most important properties of a physical system, but are not commonplace in biology. We derived a conservation law from the basic model for viral infections which consists in a small set of ordinary differential equations. We challenged the conservation law experimentally for the case of a virus infection in a cell culture. We found that the derived, conserved quantity remained almost constant throughout the infection period, implying that the derived conservation law holds in this biological system. We also suggest a potential use for the conservation law in evaluating the accuracy of experimental measurements. PMID:25882746

  5. Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015.

    PubMed

    Schuler-Faccini, Lavinia; Ribeiro, Erlane M; Feitosa, Ian M L; Horovitz, Dafne D G; Cavalcanti, Denise P; Pessoa, André; Doriqui, Maria Juliana R; Neri, Joao Ivanildo; Neto, Joao Monteiro de Pina; Wanderley, Hector Y C; Cernach, Mirlene; El-Husny, Antonette S; Pone, Marcos V S; Serao, Cassio L C; Sanseverino, Maria Teresa V

    2016-01-01

    In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil's 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear

  6. A Case of Diabetic Ketoacidosis Following Chikungunya Virus Infection.

    PubMed

    Tolokh, Illya; Laux, Timothy; Kim, Daniel

    2015-08-01

    Chikungunya is a mosquito-borne viral disease that has recently become endemic in the Caribbean, including the island of Puerto Rico. We present the case of a 50-year-old Puerto Rican man who traveled to St. Louis for business and was diagnosed with acute chikungunya virus infection with atypical features causing diabetic ketoacidosis. This case highlights the need to keep tropical infectious diseases on the differential diagnosis in appropriate individuals and the ways in which tropical infectious diseases can masquerade as part of common presentations. PMID:26033023

  7. Lessons for tuberculosis vaccines from respiratory virus infection.

    PubMed

    Beverley, Peter Charles Leonard; Tchilian, Elma Zaven

    2008-10-01

    There is a worldwide epidemic of increasingly drug-resistant TB. Bacillus Calmette-Guérin vaccination provides partial protection against disseminated disease in infants but poor protection against later pulmonary TB. Cell-mediated protection against respiratory virus infections requires the presence of T cells in lung tissues, and the most effective prime-boost immunizations for Mycobacterium tuberculosis also induce lung-resident lymphocytes. These observations need to be taken into account when designing future vaccines against M. tuberculosis. PMID:18844591

  8. Care of the Human Immunodeficiency Virus-Infected Menopausal Woman

    PubMed Central

    Cejtin, Helen E.

    2012-01-01

    More women than ever before are both Human Immunodeficiency Virus-infected and menopausal, because of increased survival and more frequent diagnosis in older women. Such a woman has the combined burden of her infection, its treatment, comorbid conditions, and aging. Thus she is at risk for a variety of problems such as disorders of bone mineral density and deficiencies in cognitive functioning. In addition to this, she experiences menopause in a unique fashion, with more symptoms and perhaps at an earlier age. The clinician caring for her must take a proactive approach to this multitude of factors that may affect her health and well-being. PMID:22284959

  9. Proteomic Analysis of Mitochondrial-Associated ER Membranes (MAM) during RNA Virus Infection Reveals Dynamic Changes in Protein and Organelle Trafficking

    PubMed Central

    Horner, Stacy M.; Wilkins, Courtney; Badil, Samantha; Iskarpatyoti, Jason; Gale, Michael

    2015-01-01

    RIG-I pathway signaling of innate immunity against RNA virus infection is organized between the ER and mitochondria on a subdomain of the ER called the mitochondrial-associated ER membrane (MAM). The RIG-I adaptor protein MAVS transmits downstream signaling of antiviral immunity, with signaling complexes assembling on the MAM in association with mitochondria and peroxisomes. To identify components that regulate MAVS signalosome assembly on the MAM, we characterized the proteome of MAM, ER, and cytosol from cells infected with either chronic (hepatitis C) or acute (Sendai) RNA virus infections, as well as mock-infected cells. Comparative analysis of protein trafficking dynamics during both chronic and acute viral infection reveals differential protein profiles in the MAM during RIG-I pathway activation. We identified proteins and biochemical pathways recruited into and out of the MAM in both chronic and acute RNA viral infections, representing proteins that drive immunity and/or regulate viral replication. In addition, by using this comparative proteomics approach, we identified 3 new MAVS-interacting proteins, RAB1B, VTN, and LONP1, and defined LONP1 as a positive regulator of the RIG-I pathway. Our proteomic analysis also reveals a dynamic cross-talk between subcellular compartments during both acute and chronic RNA virus infection, and demonstrates the importance of the MAM as a central platform that coordinates innate immune signaling to initiate immunity against RNA virus infection. PMID:25734423

  10. Drug repurposing of minocycline against dengue virus infection.

    PubMed

    Leela, Shilpa Lekshmi; Srisawat, Chatchawan; Sreekanth, Gopinathan Pillai; Noisakran, Sansanee; Yenchitsomanus, Pa-Thai; Limjindaporn, Thawornchai

    2016-09-01

    Dengue virus infection is one of the most common arthropod-borne viral diseases. A complex interplay between host and viral factors contributes to the severity of infection. The antiviral effects of three antibiotics, lomefloxacin, netilmicin, and minocycline, were examined in this study, and minocycline was found to be a promising drug. This antiviral effect was confirmed in all four serotypes of the virus. The effects of minocycline at various stages of the viral life cycle, such as during viral RNA synthesis, intracellular envelope protein expression, and the production of infectious virions, were examined and found to be significantly reduced by minocycline treatment. Minocycline also modulated host factors, including the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2). The transcription of antiviral genes, including 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase 3 (OAS3), and interferon α (IFNA), was upregulated by minocycline treatment. Therefore, the antiviral activity of minocycline may have a potential clinical use against Dengue virus infection. PMID:27396621

  11. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    SciTech Connect

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  12. Global Reprogramming of Host SUMOylation during Influenza Virus Infection

    PubMed Central

    Domingues, Patricia; Golebiowski, Filip; Tatham, Michael H.; Lopes, Antonio M.; Taggart, Aislynn; Hay, Ronald T.; Hale, Benjamin G.

    2015-01-01

    Summary Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here, we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome remodeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection. PMID:26549460

  13. Senescence affects endothelial cells susceptibility to dengue virus infection.

    PubMed

    AbuBakar, Sazaly; Shu, Meng-Hooi; Johari, Jefree; Wong, Pooi-Fong

    2014-01-01

    Alteration in the endothelium leading to increased vascular permeability contributes to plasma leakage seen in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). An earlier study showed that senescent endothelial cells (ECs) altered the ECs permeability. Here we investigated the susceptibility of senescing human umbilical vein endothelial cells (HUVECs) to dengue virus infection and determined if dengue virus infection induces HUVECs senescence. Our results suggest that DENV type-2 (DENV-2) foci forming unit (FFU) and extracellular virus RNA copy number were reduced by at least 35% and 85% in infection of the intermediate young and early senescent HUVECs, respectively, in comparison to infection of young HUVECs. No to low infectivity was recovered from infection of late senescent HUVECs. DENV infection also increases the percentage of HUVECs expressing senescence-associated (SA)-β-gal, cells arrested at the G2/M phase or 4N DNA content stage and cells with enlarged morphology, indicative of senescing cells. Alteration of HUVECs morphology was recorded using impedance-based real-time cell analysis system following DENV-2 infection. These results suggest that senescing HUVECs do not support DENV infection and DENV infection induces HUVECs senescence. The finding highlights the possible role of induction of senescence in DENV infection of the endothelial cells. PMID:24782642

  14. ZIKA VIRUS INFECTION; VERTICAL TRANSMISSION AND FOETAL CONGENITAL ANOMALIES.

    PubMed

    Abbasi, Aziz-un-Nisa

    2016-01-01

    Zika virus (ZIKV) is an arbovirus belonging to flaviviridae family that includes Dengue, West Nile, and Yellow Fever among others. Zika virus was first discovered in 1947 in Zika forest of Uganda. It is a vector borne disease, which has been sporadically reported mostly from Africa, Pacific islands and Southeast Asia since its discovery. ZIKV infection presents as a mild illness with symptoms lasting for several days to a week after the bite of an infected mosquito. Majority of the patients have low grade fever, rash, headaches, joints pain, myalgia, and flu like symptoms. Pregnant women are more vulnerable to ZIKV infection and serious congenital anomalies can occur in foetus through trans-placental transmission. The gestation at which infection is acquired is important. Zika virus infection acquired in early pregnancy poses greater risk. There is no evidence so far about transmission through breast milk. Foetal microcephaly, Gillian Barre syndrome and other neurological and autoimmune syndromes have been reported in areas where Zika outbreaks have occurred. As infection is usually very mild no specific treatment is required. Pregnant women may be advised to take rest, get plenty of fluids. For fever and pain they can take antipyretics like paracetamol. So far no specific drugs or vaccines are available against Zika Virus Infection so prevention is the mainstay against this diseases. As ZIKV infection is a vector borne disease, prevention can be a multi-pronged strategy. These entail vector control interventions, personal protection, environmental sanitation and health education among others. PMID:27323550

  15. Analysis of resistance and tolerance to virus infection in Drosophila.

    PubMed

    Merkling, Sarah H; van Rij, Ronald P

    2015-07-01

    Host defense to virus infection involves both resistance mechanisms that reduce viral burden and tolerance mechanisms that limit detrimental effects of infection. The fruit fly, Drosophila melanogaster, has emerged as a model for identifying and characterizing the genetic basis of resistance and tolerance. This protocol describes how to analyze host responses to virus infection in Drosophila, and it covers the preparation of virus stocks, experimental inoculation of flies and assessment of host survival and virus production, which are indicative of resistance or tolerance. It also provides guidance on how to account for recently identified confounding factors, including natural genetic variation in the pastrel locus and contamination of fly stocks with persistent viruses and the symbiotic bacterium Wolbachia. Our protocol aims to be accessible to newcomers to the field and, although optimized for virus research using Drosophila, some of the techniques could be adapted to other host organisms and/or other microbial pathogens. Preparation of fly stocks requires ∼1 month, virus stock preparation requires 17-20 d, virus injection and survival assays require 10-15 d and virus titration requires 14 d. PMID:26110714

  16. Severe Sepsis and Septic Shock Associated with Chikungunya Virus Infection, Guadeloupe, 2014

    PubMed Central

    Rollé, Amélie; Schepers, Kinda; Cassadou, Sylvie; Curlier, Elodie; Madeux, Benjamin; Hermann-Storck, Cécile; Fabre, Isabelle; Lamaury, Isabelle; Tressières, Benoit; Thiery, Guillaume

    2016-01-01

    During a 2014 outbreak, 450 patients with confirmed chikungunya virus infection were admitted to the University Hospital of Pointe-à-Pitre, Guadeloupe. Of these, 110 were nonpregnant adults; 42 had severe disease, and of those, 25 had severe sepsis or septic shock and 12 died. Severe sepsis may be a rare complication of chikungunya virus infection. PMID:27088710

  17. Influenza virus infections in the tropics during the first year of life.

    PubMed

    Libraty, Daniel H; Zhang, Lei; Caponpon, Mercydina; Capeding, Rosario Z

    2015-08-01

    Pediatric influenza virus infections in the tropics, particularly during infancy, are not well described. We identified influenza virus infections among infants with non-dengue acute undifferentiated febrile illnesses in San Pablo, Laguna, Philippines, as part of an ongoing clinical study of dengue virus infections during infancy. We found that 31% of infants with non-dengue acute undifferentiated febrile illnesses in San Pablo, Laguna, Philippines, had influenza virus infections. The majority were influenza A virus infections and outpatient cases. The infant ages were 11.1 [9.8-13.0] months (median [95% confidence interval]), and the cases clustered between June and December. Influenza episodes are a common cause of non-dengue acute undifferentiated febrile illnesses in the tropics during the first year of life. PMID:25828834

  18. Cellular chaperones and folding enzymes are vital contributors to membrane bound replication and movement complexes during plant RNA virus infection

    PubMed Central

    Verchot, Jeanmarie

    2012-01-01

    Cellular chaperones and folding enzymes play central roles in the formation of positive-strand and negative-strand RNA virus infection. This article examines the key cellular chaperones and discusses evidence that these factors are diverted from their cellular functions to play alternative roles in virus infection. For most chaperones discussed, their primary role in the cell is to ensure protein quality control. They are system components that drive substrate protein folding, complex assembly or disaggregation. Their activities often depend upon co-chaperones and ATP hydrolysis. During plant virus infection, Hsp70 and Hsp90 proteins play central roles in the formation of membrane-bound replication complexes for certain members of the tombusvirus, tobamovirus, potyvirus, dianthovirus, potexvirus, and carmovirus genus. There are several co-chaperones, including Yjd1, RME-8, and Hsp40 that associate with the bromovirus replication complex, pomovirus TGB2, and tospovirus Nsm movement proteins. There are also examples of plant viruses that rely on chaperone systems in the endoplasmic reticulum (ER) to support cell-to-cell movement. TMV relies on calreticulin to promote virus intercellular transport. Calreticulin also resides in the plasmodesmata and plays a role in calcium sequestration as well as glycoprotein folding. The pomovirus TGB2 interacts with RME-8 in the endosome. The potexvirus TGB3 protein stimulates expression of ER resident chaperones via the bZIP60 transcription factor. Up-regulating factors involved in protein folding may be essential to handling the load of viral proteins translated along the ER. In addition, TGB3 stimulates SKP1 which is a co-factor in proteasomal degradation of cellular proteins. Such chaperones and co-factors are potential targets for antiviral defense. PMID:23230447

  19. Total knee arthroplasty in human immunodeficiency virus-infected hemophiliacs.

    PubMed

    Unger, A S; Kessler, C M; Lewis, R J

    1995-08-01

    Twenty-six knee arthroplasties were performed in 15 patients with hemophilia A and human immunodeficiency virus infection from 1984 to 1991. Patient age range was 27 to 48 years. After an average follow-up period of 6.4 years (range, 1-9 years) all patients were alive and none of the implants had become infected. T4 lymphocyte counts showed some deterioration, which was not clinically significant. All of the patients were improved following surgery. Nineteen implants were rated excellent, four good, and three fair. Infection with human immunodeficiency virus did not adversely affect the clinical outcome of knee arthroplasty at follow-up periods up to 9 years. PMID:8523002

  20. Neutralizing antibodies in Borna disease virus-infected rats.

    PubMed Central

    Hatalski, C G; Kliche, S; Stitz, L; Lipkin, W I

    1995-01-01

    Borna disease is a neurologic syndrome caused by infection with a nonsegmented, negative-strand RNA virus, Borna disease virus. Infected animals have antibodies to two soluble viral proteins, p40 and p23, and a membrane-associated viral glycoprotein, gp18. We examined the time course for the development of neutralization activity and the expression of antibodies to individual viral proteins in sera of infected rats. The appearance of neutralizing activity correlated with the development of immunoreactivity to gp18, but not p40 or p23. Monospecific and monoclonal antibodies to native gp18 and recombinant nonglycosylated gp18 were also found to have neutralizing activity and to immunoprecipitate viral particles or subparticles. These findings suggest that gp18 is likely to be present on the surface of the viral particles and is likely to contain epitopes important for virus neutralization. PMID:7815538

  1. Influenza A Virus Infection, Innate Immunity, and Childhood

    PubMed Central

    Coates, Bria M.; Staricha, Kelly L.; Wiese, Kristin M.; Ridge, Karen M.

    2016-01-01

    Infection with influenza A virus is responsible for considerable morbidity and mortality in children worldwide. While it is apparent that adequate activation of the innate immune system is essential for pathogen clearance and host survival, an excessive inflammatory response to infection is detrimental to the young host. A review of the literature indicates that innate immune responses change throughout childhood. Whether these changes are genetically programmed or triggered by environmental cues is unknown. The objectives of this review are to summarize the role of innate immunity in influenza A virus infection in the young child and to highlight possible differences between children and adults that may make children more susceptible to severe influenza A infection. A better understanding of age-related differences in innate immune signaling will be essential to improve care for this high-risk population. PMID:26237589

  2. Genetic variation of occult hepatitis B virus infection

    PubMed Central

    Zhu, Hui-Lan; Li, Xu; Li, Jun; Zhang, Zhen-Hua

    2016-01-01

    Occult hepatitis B virus infection (OBI), characterized as the persistence of hepatitis B virus (HBV) surface antigen (HBsAg) seronegativity and low viral load in blood or liver, is a special form of HBV infection. OBI may be related mainly to mutations in the HBV genome, although the underlying mechanism of it remains to be clarified. Mutations especially within the immunodominant “α” determinant of S protein are “hot spots” that could contribute to the occurrence of OBI via affecting antigenicity and immunogenicity of HBsAg or replication and secretion of virion. Clinical reports account for a large proportion of previous studies on OBI, while functional analyses, especially those based on full-length HBV genome, are rare. PMID:27053845

  3. Acute Human Inkoo and Chatanga Virus Infections, Finland

    PubMed Central

    Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-01-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001–2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children. PMID:27088268

  4. The Impact of Wolbachia on Virus Infection in Mosquitoes

    PubMed Central

    Johnson, Karyn N.

    2015-01-01

    Mosquito-borne viruses such as dengue, West Nile and chikungunya viruses cause significant morbidity and mortality in human populations. Since current methods are not sufficient to control disease occurrence, novel methods to control transmission of arboviruses would be beneficial. Recent studies have shown that virus infection and transmission in insects can be impeded by co-infection with the bacterium Wolbachia pipientis. Wolbachia is a maternally inherited endosymbiont that is commonly found in insects, including a number of mosquito vector species. In Drosophila, Wolbachia mediates antiviral protection against a broad range of RNA viruses. This discovery pointed to a potential strategy to interfere with mosquito transmission of arboviruses by artificially infecting mosquitoes with Wolbachia. This review outlines research on the prevalence of Wolbachia in mosquito vector species and the impact of antiviral effects in both naturally and artificially Wolbachia-infected mosquitoes. PMID:26556361

  5. Background review for diagnostic test development for Zika virus infection

    PubMed Central

    Charrel, Rémi N; Leparc-Goffart, Isabelle; Pas, Suzan; de Lamballerie, Xavier; Koopmans, Marion; Reusken, Chantal

    2016-01-01

    Abstract Objective To review the state of knowledge about diagnostic testing for Zika virus infection and identify areas of research needed to address the current gaps in knowledge. Methods We made a non-systematic review of the published literature about Zika virus and supplemented this with information from commercial diagnostic test kits and personal communications with researchers in European preparedness networks. The review covered current knowledge about the geographical spread, pathogen characteristics, life cycle and infection kinetics of the virus. The available molecular and serological tests and biosafety issues are described and discussed in the context of the current outbreak strain. Findings We identified the following areas of research to address current knowledge gaps: (i) an urgent assessment of the laboratory capacity and capability of countries to detect Zika virus; (ii) rapid and extensive field validation of the available molecular and serological tests in areas with and without Zika virus transmission, with a focus on pregnant women; (iii) monitoring the genomic diversity of circulating Zika virus strains; (iv) prospective studies into the virus infection kinetics, focusing on diagnostic sampling (specimen types, combinations and timings); and (v) developing external quality assessments for molecular and serological testing, including differential diagnosis for similar viruses and symptom clusters. The availability of reagents for diagnostic development (virus strains and antigens, quantified viral ribonucleic acid) needs to be facilitated. Conclusion An international laboratory response is needed, including preparation of protocols for prospective studies to address the most pressing information needs. PMID:27516635

  6. Permissive and restricted virus infection of murine embryonic stem cells.

    PubMed

    Wash, Rachael; Calabressi, Sabrina; Franz, Stephanie; Griffiths, Samantha J; Goulding, David; Tan, E-Pien; Wise, Helen; Digard, Paul; Haas, Jürgen; Efstathiou, Stacey; Kellam, Paul

    2012-10-01

    Recent RNA interference (RNAi) studies have identified many host proteins that modulate virus infection, but small interfering RNA 'off-target' effects and the use of transformed cell lines limit their conclusiveness. As murine embryonic stem (mES) cells can be genetically modified and resources exist where many and eventually all known mouse genes are insertionally inactivated, it was reasoned that mES cells would provide a useful alternative to RNAi screens. Beyond allowing investigation of host-pathogen interactions in vitro, mES cells have the potential to differentiate into other primary cell types, as well as being used to generate knockout mice for in vivo studies. However, mES cells are poorly characterized for virus infection. To investigate whether ES cells can be used to explore host-virus interactions, this study characterized the responses of mES cells following infection by herpes simplex virus type 1 (HSV-1) and influenza A virus. HSV-1 replicated lytically in mES cells, although mES cells were less permissive than most other cell types tested. Influenza virus was able to enter mES cells and express some viral proteins, but the replication cycle was incomplete and no infectious virus was produced. Knockdown of the host protein AHCYL1 in mES cells reduced HSV-1 replication, showing the potential for using mES cells to study host-virus interactions. Transcriptional profiling, however, indicated the lack of an efficient innate immune response in these cells. mES cells may thus be useful to identify host proteins that play a role in virus replication, but they are not suitable to determine factors that are involved in innate host defence. PMID:22815272

  7. Permissive and restricted virus infection of murine embryonic stem cells

    PubMed Central

    Wash, Rachael; Calabressi, Sabrina; Franz, Stephanie; Griffiths, Samantha J.; Goulding, David; Tan, E-Pien; Wise, Helen; Digard, Paul; Haas, Jürgen; Efstathiou, Stacey

    2012-01-01

    Recent RNA interference (RNAi) studies have identified many host proteins that modulate virus infection, but small interfering RNA ‘off-target’ effects and the use of transformed cell lines limit their conclusiveness. As murine embryonic stem (mES) cells can be genetically modified and resources exist where many and eventually all known mouse genes are insertionally inactivated, it was reasoned that mES cells would provide a useful alternative to RNAi screens. Beyond allowing investigation of host–pathogen interactions in vitro, mES cells have the potential to differentiate into other primary cell types, as well as being used to generate knockout mice for in vivo studies. However, mES cells are poorly characterized for virus infection. To investigate whether ES cells can be used to explore host–virus interactions, this study characterized the responses of mES cells following infection by herpes simplex virus type 1 (HSV-1) and influenza A virus. HSV-1 replicated lytically in mES cells, although mES cells were less permissive than most other cell types tested. Influenza virus was able to enter mES cells and express some viral proteins, but the replication cycle was incomplete and no infectious virus was produced. Knockdown of the host protein AHCYL1 in mES cells reduced HSV-1 replication, showing the potential for using mES cells to study host–virus interactions. Transcriptional profiling, however, indicated the lack of an efficient innate immune response in these cells. mES cells may thus be useful to identify host proteins that play a role in virus replication, but they are not suitable to determine factors that are involved in innate host defence. PMID:22815272

  8. Quantifying homologous and heterologous antibody titre rises after influenza virus infection.

    PubMed

    Freeman, G; Perera, R A P M; Ngan, E; Fang, V J; Cauchemez, S; Ip, D K M; Peiris, J S M; Cowling, B J

    2016-08-01

    Most influenza virus infections are associated with mild disease. One approach to estimate the occurrence of influenza virus infections in individuals is via repeated measurement of humoral antibody titres. We used baseline and convalescent antibody titres measured by haemagglutination inhibition (HI) and viral neutralization (VN) assays against influenza A(H1N1), A(H3N2) and B viruses to investigate the characteristics of antibody rises following virologically confirmed influenza virus infections in participants in a community-based study. Multivariate models were fitted in a Bayesian framework to characterize the distribution of changes in antibody titres following influenza A virus infections. In 122 participants with PCR-confirmed influenza A virus infection, homologous antibody titres rose by geometric means of 1·2- to 10·2-fold after infection with A(H1N1), A(H3N2) and A(H1N1)pdm09. Significant cross-reactions were observed between A(H1N1)pdm09 and seasonal A(H1N1). Antibody titre rises for some subtypes and assays varied by age, receipt of oseltamivir treatment, and recent receipt of influenza vaccination. In conclusion, we provided a quantitative description of the mean and variation in rises in influenza virus antibody titres following influenza virus infection. The multivariate patterns in boosting of antibody titres following influenza virus infection could be taken into account to improve estimates of cumulative incidence of infection in seroepidemiological studies. PMID:27018720

  9. Parainfluenza Virus 5 Expressing the G Protein of Rabies Virus Protects Mice after Rabies Virus Infection

    PubMed Central

    Huang, Ying; Chen, Zhenhai; Huang, Junhua

    2014-01-01

    Rabies remains a major public health threat around the world. Once symptoms appear, there is no effective treatment to prevent death. In this work, we tested a recombinant parainfluenza virus 5 (PIV5) strain expressing the glycoprotein (G) of rabies (PIV5-G) as a therapy for rabies virus infection: we have found that PIV5-G protected mice as late as 6 days after rabies virus infection. PIV5-G is a promising vaccine for prevention and treatment of rabies virus infection. PMID:25552723

  10. Seroepidemiology of Asymptomatic Dengue Virus Infection in Jeddah, Saudi Arabia

    PubMed Central

    Jamjoom, Ghazi A.; Azhar, Esam I.; Kao, Moujahid A.; Radadi, Raja M.

    2016-01-01

    BACKGROUND Although virologically confirmed dengue fever has been recognized in Jeddah, Saudi Arabia, since 1994, causing yearly outbreaks, no proper seroepidemiologic studies on dengue virus have been conducted in this region. Such studies can define the extent of infection by this virus and estimate the proportion that may result in disease. The aim of this study was to measure the seroprevalence of past dengue virus infection in healthy Saudi nationals from different areas in the city of Jeddah and to investigate demographic and environmental factors that may increase exposure to infection. METHODS Sera were collected from 1984 Saudi subjects attending primary health care centers in six districts of Jeddah. These included general patients of various ages seeking routine vaccinations, antenatal care or treatment of different illnesses excluding fever or suspected dengue. A number of blood donors were also tested. Serum samples were tested by enzyme immunoassay (EIA) for IgG antibodies to dengue viruses 1, 2, 3, 4. A questionnaire was completed for each patient recording various anthropometric data and factors that may indicate possible risk of exposure to mosquito bites and dengue infection. Patients with missing data and those who reported a history of dengue fever were excluded from analysis, resulting in a sample of 1939 patients to be analyzed. RESULTS The overall prevalence of dengue virus infection as measured by anti-dengue IgG antibodies from asymptomatic residents in Jeddah was 47.8% (927/1939) and 37% (68/184) in blood donors. Infection mostly did not result in recognizable disease, as only 19 of 1956 subjects with complete information (0.1%) reported having dengue fever in the past. Anti dengue seropositivity increased with age and was higher in males than females and in residents of communal housing and multistory buildings than in villas. One of the six districts showed significant increase in exposure rate as compared to the others. Availability of

  11. Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells

    SciTech Connect

    Redfield, D.C.; Richman, D.D.; Oxman, M.N.; Kronenberg, L.H.

    1981-06-01

    Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays.

  12. Gibberellins and the break of bud dormancy in virus-infected stem cuttings of Euphorbia pulcherrima.

    PubMed

    Nath, S; Mandahar, C L; Gulati, A

    1979-10-15

    Break in bud dormancy in virus-infected stem cuttings of Euphorbia pulcherrima occurs because of the higher quantity of gibberellins present in them than in healthy cuttings in the dormant period of the plant. PMID:499409

  13. Dengue and hepatitis E virus infection in pregnant women in Eastern Sudan, a challenge for diagnosis in an endemic area

    PubMed Central

    Elduma, Adel Hussein; Osman, Waleed Mohammed

    2014-01-01

    Dengue fever and hepatitis E virus infection are both a public health problem in developing countries due to poor sanitation. Infection with viral hepatitis and dengue fever can present with similar clinical such and fever, headache and abortion. This study was conducted in Port-Sudan city in the eastern part of the country. ELISA and Real Time PCR tests were used to detect the infection. A total number of 39 pregnant women with a mean age 26 ±7.8 were included in the study. All of them had fever, 32 (92.3%) admitted with headache, 11 (28.2%) of them had vomiting, and abortion was reported in two cases (5.1%). The study showed that 4 (10.3%) of pregnant women were positive for the Hepatitis E virus, 5 (12.8%) positive for Dengue virus IgG, and only one sample (2.6%) was positive for IgM capture ELISA and real time PCR. Death due to hepatitis E infection was reported in one case with 7th month of pregnancy. Most of hepatitis cases were reported in the central sector of the Portsudan city. The diagnosis of hepatitis E virus and dengue virus in an endemic area is a great challenge for health care staff working in these areas. Both Dengue virus and Hepatitis E virus infection should be considered in pregnant women especially in similar settings. PMID:25995787

  14. Resistance/susceptibility to lethal Sendai virus infection genetically linked to a mucociliary transport polymorphism.

    PubMed Central

    Brownstein, D G

    1987-01-01

    Linkage was tested between a mucociliary transport polymorphism and resistance/susceptibility to lethal Sendai virus infection in segregant hybrid mice of C57BL/6J and DBA/2J parents. The distribution of paired phenotypes for tracheal mucociliary transport rates and susceptibility to lethal Sendai virus infection in 171 F1 X DBA/2J mice showed strong interaction of the parental phenotypes. PMID:3033294

  15. Zika virus infection spread through saliva--a truth or myth?

    PubMed

    Siqueira, Walter Luiz; Moffa, Eduardo Buozi; Mussi, Maria Carolina Martins; Machado, Maria Aparecida de Andrade Moreira

    2016-01-01

    In this Point-of-view article we highlighted some features related to saliva and virus infection, in special for zika virus. In addition, we pointed out the potential oral problems caused by a microcephaly originated by a zika virus infection. In the end the, we demonstrated the importance of a more comprehensive exploration of saliva and their components as a fluid for diagnostic and therapeutic approaches on oral and systemic diseases. PMID:26981761

  16. [IMMUNE SYSTEM DATA IN PATIENTS WITH PERSISTENT RECURENT HERPES VIRUS INFECTIONS IN DYNAMICS OF COMPLEX THERAPY].

    PubMed

    Rudenko, M Yu

    2015-01-01

    The positive clinical, serolgical and immunological effects of Glutamyl-Triptophan in patients on persistent herpes virus infections are shown. Treatment resulted in the increase of avidity on HSV 1, HSV 2, CMV, EBV antibody, the levels of CD3+-, ICD8+-, CD16+-, CD3+HLA-DR+- (%, abs) and.CD3+CD25t-cells (%), that indicates the optimization of the immune systemdata. The data received allow to recommend Bestim for patients with persistent herpes virus infections. PMID:27089710

  17. Ultrastructural studies on dengue virus infection of human lymphoblasts.

    PubMed Central

    Sriurairatna, S; Bhamarapravati, N; Diwan, A R; Halstead, S B

    1978-01-01

    Ultrastructural studies of dengue-2 virus-infected lymphoblastoid Raji cells showed that the virus induced an increase in the size of the rough endoplasmic reticula (RER) and that the replication of the virus was confined to the cisternae of these RER. The proliferating RER formed cytoplasmic inclusions that could be seen by light microscopy. This observation could be used as evidence of a cytopathogenic effect of dengue virus on infected Rajii cells in routine cultures. Accumulation of virions in the infected cells was minimal in comparison with other cell systems, however. Sporadic clusters of mature virions were often seen on the plasma membrane. These extracellular virions were distributed adjacent to the virus-bearing RER and were presumably released virions. Vertical transmission of the virus was evident in mitotic lymphoblasts. The replication pattern of dengue virus in lymphoblastoid cells suggests that efforts should be made to determine whether blast-transformed lymphocytes, numerous in secondary dengue infections, support dengue virus replication in vivo. Images PMID:669791

  18. Inhibition of Mayaro virus infection by bovine lactoferrin.

    PubMed

    Carvalho, Carlos A M; Sousa, Ivanildo P; Silva, Jerson L; Oliveira, Andréa C; Gonçalves, Rafael B; Gomes, Andre M O

    2014-03-01

    Mayaro virus (MAYV) is an arbovirus linked to several sporadic outbreaks of a highly debilitating febrile illness in many regions of South America. MAYV is on the verge of urbanization from the Amazon region and no effective antiviral intervention is available against human infections. Our aim was to investigate whether bovine lactoferrin (bLf), an iron-binding glycoprotein, could hinder MAYV infection. We show that bLf promotes a strong inhibition of virus infection with no cytotoxic effects. Monitoring the effect of bLf on different stages of infection, we observed that virus entry into the cell is the heavily compromised event. Moreover, we found that binding of bLf to the cell is highly dependent on the sulfation of glycosaminoglycans, suggesting that bLf impairs virus entry by blocking these molecules. Our findings highlight the antiviral potential of bLf and reveal an effective strategy against one of the major emerging human pathogens in the neotropics. PMID:24606707

  19. Rabies virus infects mouse and human lymphocytes and induces apoptosis.

    PubMed Central

    Thoulouze, M I; Lafage, M; Montano-Hirose, J A; Lafon, M

    1997-01-01

    Attenuated and highly neurovirulent rabies virus strains have distinct cellular tropisms. Highly neurovirulent strains such as the challenge virus standard (CVS) are highly neurotropic, whereas the attenuated strain ERA also infects nonneuronal cells. We report that both rabies virus strains infect activated murine lymphocytes and the human lymphoblastoid Jurkat T-cell line in vitro. The lymphocytes are more permissive to the attenuated ERA rabies virus strain than to the CVS strain in both cases. We also report that in contrast to that of the CVS strain, ERA viral replication induces apoptosis of infected Jurkat T cells, and cell death is concomitant with viral glycoprotein expression, suggesting that this protein has a role in the induction of apoptosis. Our data indicate that (i) rabies virus infects lymphocytes, (ii) lymphocyte infection with the attenuated rabies virus strain causes apoptosis, and (iii) apoptosis does not hinder rabies virus production. In contrast to CVS, ERA rabies virus and other attenuated rabies virus vaccines stimulate a strong immune response and are efficient live vaccines. The paradoxical finding that a rabies virus triggers a strong immune response despite the fact that it infects lymphocytes and induces apoptosis is discussed in terms of the function of apoptosis in the immune response. PMID:9311815

  20. Neuraminidase inhibitors for influenza B virus infection: efficacy and resistance

    PubMed Central

    Burnham, Andrew J.; Baranovich, Tatiana; Govorkova, Elena A.

    2013-01-01

    Many aspects of the biology and epidemiology of influenza B viruses are far less studied than for influenza A viruses, and one of these aspects is effectiveness and resistance to the clinically available antiviral drugs, the neuraminidase (NA) inhibitors (NAIs). Acute respiratory infections are one of the leading causes of death in children and adults, and influenza is among the few respiratory infections that can be prevented and treated by vaccination and antiviral treatment. Recent data has suggested that influenza B virus infections are of specific concern to pediatric patients because of the increased risk of severe disease. Treatment of influenza B is a challenging task for the following reasons: NAIs (e.g., oseltamivir and zanamivir) are the only FDA-approved class of antivirals available for treatment;the data suggest that oseltamivir is less effective than zanamivir in pediatric patients;zanamivir is not prescribed to patients younger than 7;influenza B viruses are less susceptible than influenza A viruses to NAIs in vitro;although the level of resistance to NAIs is low, the number of different molecular markers of resistance is higher than for influenza A viruses, and they are not well defined;the relationship between levels of NAI phenotypic resistance and known molecular markers, frequency of emergence, transmissibility, and fitness of NAI-resistant variants are not well established. This review presents current knowledge of the effectiveness of NAIs for influenza B virus and antiviral resistance in clinical, surveillance, and experimental studies. PMID:24013000

  1. Hepatitis during respiratory syncytial virus infection – a case report

    PubMed Central

    Kirin, Branka Kristić; Topić, Renata Zrinski; Dodig, Slavica

    2013-01-01

    Introduction: Respiratory syncytial virus (RSV) infection is the most common cause of hospitalization in infants and small children. The aim was to present a 13-months old boy diagnosed with acute airway infection, acute otitis media (AOM) and hepatitis during the RSV-infection. Material and methods: Serum catalytic activities of alkaline phosphatase (ALP), aspartate aminotranspherase (AST), alanine aminotranspherase (ALT), gamma glutamyl transpherase (GGT), lactate dehydrogenase (LD), and concentrations of bilirubin were monitored during hospitalization and at control examination. Results: The child had clinical signs and symptoms of respiratory failure, AOM, and laboratory findings of virus infection and liver disease. On admission, catalytic activities of enzymes were markedly increased, especially the activity of ALP (10333 U/L, i.e. 24-fold increase in comparison with the upper reference limit). The highest increased in AST (339 U/L, 4.5-fold), ALT (475 U/L, 10.3-fold) and LD (545 U/L, 1.5-fold) were registered on the 3rd day, and the highest increase in GGT (68 U/L, 3.1-fold) occurred on the 11th day. Seven weeks after discharge AST, ALT, GGT and LD decreased into reference range, and ALP remain mildly increased (478 U/L, 1.1 fold increase). RSV was confirmed in nasal lavage fluid. Conclusion: Laboratory results in patient with RSV infection needs to be interpreted in the light of both, respiratory and extrapulmonary manifestations of the infection, respectively. PMID:23457772

  2. Activated mouse eosinophils protect against lethal respiratory virus infection

    PubMed Central

    Percopo, Caroline M.; Dyer, Kimberly D.; Ochkur, Sergei I.; Luo, Janice L.; Fischer, Elizabeth R.; Lee, James J.; Lee, Nancy A.; Domachowske, Joseph B.

    2014-01-01

    Eosinophils are recruited to the airways as a prominent feature of the asthmatic inflammatory response where they are broadly perceived as promoting pathophysiology. Respiratory virus infections exacerbate established asthma; however, the role of eosinophils and the nature of their interactions with respiratory viruses remain uncertain. To explore these questions, we established acute infection with the rodent pneumovirus, pneumonia virus of mice (PVM), in 3 distinct mouse models of Th2 cytokine–driven asthmatic inflammation. We found that eosinophils recruited to the airways of otherwise naïve mice in response to Aspergillus fumigatus, but not ovalbumin sensitization and challenge, are activated by and degranulate specifically in response to PVM infection. Furthermore, we demonstrate that activated eosinophils from both Aspergillus antigen and cytokine-driven asthma models are profoundly antiviral and promote survival in response to an otherwise lethal PVM infection. Thus, although activated eosinophils within a Th2-polarized inflammatory response may have pathophysiologic features, they are also efficient and effective mediators of antiviral host defense. PMID:24297871

  3. Hepatitis B virus infection and metabolic syndrome: fact or fiction?

    PubMed

    Wang, Chia-Chi; Tseng, Tai-Chung; Kao, Jia-Horng

    2015-01-01

    Although hepatitis C virus infection is known to be linked with insulin resistance, dyslipidemia, and hepatic steatosis, the relationship between hepatitis B virus (HBV) infection and metabolic factors remains unclear. HBV infection is a health problem worldwide, especially in endemic regions such as Asia and Africa. It induces liver decompensation, cirrhosis, hepatocellualr carcinoma, and premature mortality. The prevalence of metabolic syndrome continues to increase in parallel with the epidemic of obesity, which is closely associated with the development of diabetes, cardiovascular disease, or even cancer. The systemic review shows that chronic HBV infection protects against instead of promotes fatty liver. The mechanism is possibly due to a lower frequency of dyslipidemia profile in patients with chronic HBV infection. The association of HBV with metabolic syndrome, insulin resistance, and the risk of arteriosclerosis is still inconclusive. In addition, obesity, diabetes, and metabolic syndrome may accelerate the progression of liver disease in patients with chronic HBV infection and synergistically induce cirrhosis or even hepatocellualr carcinoma development. PMID:25092429

  4. A dual drug regimen synergistically blocks human parainfluenza virus infection

    PubMed Central

    Bailly, Benjamin; Dirr, Larissa; El-Deeb, Ibrahim M.; Altmeyer, Ralf; Guillon, Patrice; von Itzstein, Mark

    2016-01-01

    Human parainfluenza type-3 virus (hPIV-3) is one of the principal aetiological agents of acute respiratory illness in infants worldwide and also shows high disease severity in the elderly and immunocompromised, but neither therapies nor vaccines are available to treat or prevent infection, respectively. Using a multidisciplinary approach we report herein that the approved drug suramin acts as a non-competitive in vitro inhibitor of the hPIV-3 haemagglutinin-neuraminidase (HN). Furthermore, the drug inhibits viral replication in mammalian epithelial cells with an IC50 of 30 μM, when applied post-adsorption. Significantly, we show in cell-based drug-combination studies using virus infection blockade assays, that suramin acts synergistically with the anti-influenza virus drug zanamivir. Our data suggests that lower concentrations of both drugs can be used to yield high levels of inhibition. Finally, using NMR spectroscopy and in silico docking simulations we confirmed that suramin binds HN simultaneously with zanamivir. This binding event occurs most likely in the vicinity of the protein primary binding site, resulting in an enhancement of the inhibitory potential of the N-acetylneuraminic acid-based inhibitor. This study offers a potentially exciting avenue for the treatment of parainfluenza infection by a combinatorial repurposing approach of well-established approved drugs. PMID:27053240

  5. Quantification of liver fibrosis in chronic hepatitis B virus infection

    PubMed Central

    Jieanu, CF; Ungureanu, BS; Săndulescu, DL; Gheonea, IA; Tudorașcu, DR; Ciurea, ME; Purcărea, VL

    2015-01-01

    Chronic hepatitis B virus infection (HBV) is considered a global public issue with more than 78.000 people per year dying of its evolution. With liver transplantation as the only viable therapeutic option but only in end-stage disease, hepatitis B progression may generally be influenced by various factors. Assessing fibrosis stage plays an important part in future decisions on the patients’ wealth with available antiviral agents capable of preventing fibrosis passing to an end-stage liver disease. Several methods have been taken into consideration as an alternative for HBV quantification status, such as imaging techniques and serum based biomarkers. Magnetic resonance imaging, ultrasound, and elastography are considered non-invasive imaging techniques frequently used to quantify disease progression as well as patients future prognostic. Consequently, both direct and indirect biomarkers have been studied for differentiating between fibrosis stages. This paper reviews the current standings in HBV non-invasive liver fibrosis quantification, presenting the prognostic factors and available assessment procedures that might eventually replace liver biopsy. PMID:26351528

  6. [Epidemiology of hepatitis E virus infection in Spain].

    PubMed

    Echevarría, José Manuel; Fogeda, Marta; Avellón, Ana

    2015-04-01

    The general features of the epidemiology and ecology of hepatitis E virus in Spain are already known after 20 years of investigations. Genotype 3 strains, mainly from sub-genotype 3f, circulated among swine livestock and certain wild mammals, and would be sporadically transmitted to humans through direct contact with the reservoirs or by consumption of foods derived from them. Bivalve shellfish contaminated by hepatitis E virus from sewage could also play a role in transmission. Although the interpretation of results from seroprevalence studies in low endemic settings is still controversial, antibody to hepatitis E virus displays an overall prevalence less than 10% among the population of Spain, increasing significantly with age. From the, approximately, 150 cases of acute hepatitis E recorded in the international literature, males older than 40 years, suffering a mild, locally acquired disease predominate. In addition, hepatitis E might be more frequent in the North of the country than in other regions. Although the disease does not usually have a great clinical relevance, the occasional finding of cases of fulminant hepatitis, and of ribavirin-resistant, chronic hepatitis E virus infections among the immunocompromised would recommend the surveillance of the infection by the public health authority and a better implementation of specific diagnostic procedures in clinical laboratories. PMID:24447919

  7. A dual drug regimen synergistically blocks human parainfluenza virus infection

    NASA Astrophysics Data System (ADS)

    Bailly, Benjamin; Dirr, Larissa; El-Deeb, Ibrahim M.; Altmeyer, Ralf; Guillon, Patrice; von Itzstein, Mark

    2016-04-01

    Human parainfluenza type-3 virus (hPIV-3) is one of the principal aetiological agents of acute respiratory illness in infants worldwide and also shows high disease severity in the elderly and immunocompromised, but neither therapies nor vaccines are available to treat or prevent infection, respectively. Using a multidisciplinary approach we report herein that the approved drug suramin acts as a non-competitive in vitro inhibitor of the hPIV-3 haemagglutinin-neuraminidase (HN). Furthermore, the drug inhibits viral replication in mammalian epithelial cells with an IC50 of 30 μM, when applied post-adsorption. Significantly, we show in cell-based drug-combination studies using virus infection blockade assays, that suramin acts synergistically with the anti-influenza virus drug zanamivir. Our data suggests that lower concentrations of both drugs can be used to yield high levels of inhibition. Finally, using NMR spectroscopy and in silico docking simulations we confirmed that suramin binds HN simultaneously with zanamivir. This binding event occurs most likely in the vicinity of the protein primary binding site, resulting in an enhancement of the inhibitory potential of the N-acetylneuraminic acid-based inhibitor. This study offers a potentially exciting avenue for the treatment of parainfluenza infection by a combinatorial repurposing approach of well-established approved drugs.

  8. A dual drug regimen synergistically blocks human parainfluenza virus infection.

    PubMed

    Bailly, Benjamin; Dirr, Larissa; El-Deeb, Ibrahim M; Altmeyer, Ralf; Guillon, Patrice; von Itzstein, Mark

    2016-01-01

    Human parainfluenza type-3 virus (hPIV-3) is one of the principal aetiological agents of acute respiratory illness in infants worldwide and also shows high disease severity in the elderly and immunocompromised, but neither therapies nor vaccines are available to treat or prevent infection, respectively. Using a multidisciplinary approach we report herein that the approved drug suramin acts as a non-competitive in vitro inhibitor of the hPIV-3 haemagglutinin-neuraminidase (HN). Furthermore, the drug inhibits viral replication in mammalian epithelial cells with an IC50 of 30 μM, when applied post-adsorption. Significantly, we show in cell-based drug-combination studies using virus infection blockade assays, that suramin acts synergistically with the anti-influenza virus drug zanamivir. Our data suggests that lower concentrations of both drugs can be used to yield high levels of inhibition. Finally, using NMR spectroscopy and in silico docking simulations we confirmed that suramin binds HN simultaneously with zanamivir. This binding event occurs most likely in the vicinity of the protein primary binding site, resulting in an enhancement of the inhibitory potential of the N-acetylneuraminic acid-based inhibitor. This study offers a potentially exciting avenue for the treatment of parainfluenza infection by a combinatorial repurposing approach of well-established approved drugs. PMID:27053240

  9. [Acute tubulointerstitial nephritis following adenovirus and respiratory syncytial virus infection].

    PubMed

    de Suremain, A; Somrani, R; Bourdat-Michel, G; Pinel, N; Morel-Baccard, C; Payen, V

    2015-05-01

    Acute tubulointerstitial nephritis (TIN) is responsible for nearly 10% of acute renal failure (ARF) cases in children. It is mostly drug-induced, but in a few cases viruses are involved, probably by an indirect mechanism. An immune-competent 13-month-old boy was admitted to the intensive care unit for severe ARF with anuria in a context of fever, cough, and rhinorrhea lasting 1 week. The kidney biopsy performed early brought out tubulointerstitial damage with mild infiltrate of lymphocytes, without any signs of necrosis. There were no virus inclusion bodies, no interstitial hemorrhage, and no glomerular or vascular damage. Other causes of TIN were excluded: there was no biological argument for an immunological, immune, or drug-induced cause. Adenovirus (ADV) and respiratory syncytial virus (RSV) were positive in respiratory multiplex polymerase chain reaction (PCR) in nasal aspirate but not in blood, urine, and renal tissue. The patient underwent dialysis for 10 days but the response to corticosteroid therapy was quickly observed within 48 h. The mechanism of TIN associated with virus infection is unknown. However, it may be immune-mediated to be able to link severe renal dysfunction and ADV and/or RSV invasion of the respiratory tract. PMID:25842199

  10. Possible FDA-approved drugs to treat Ebola virus infection.

    PubMed

    Yuan, Shu

    2015-01-01

    There is currently no effective treatment for the Ebola virus (EBOV) thus far. Most drugs and vaccines developed to date have not yet been approved for human trials. Two FDA-approved c-AbI1 tyrosine kinase inhibitors Gleevec and Tasigna block the release of viral particles; however, their clinical dosages are much lower than the dosages required for effective EBOV suppression. An α-1,2-glucosidase inhibitor Miglustat has been shown to inhibit EBOV particle assembly and secretion. Additionally, the estrogen receptor modulators Clomiphene and Toremifene prevent membrane fusion of EBOV and 50-90% of treated mice survived after Clomiphene/Toremifene treatments. However, the uptake efficiency of Clomiphene by oral administration is very low. Thus, I propose a hypothetical treatment protocol to treat Ebola virus infection with a cumulative use of both Miglustat and Toremifene to inhibit the virus effectively and synergistically. EBOV infection induces massive apoptosis of peripheral lymphocytes. Also, cytolysis of endothelial cells triggers disseminated intravascular coagulation (DIC) and subsequent multiple organ failures. Therefore, blood transfusions and active treatments with FDA-approved drugs to treat DIC are also recommended. PMID:25984303

  11. Role of natural killer cells in innate protection against lethal ebola virus infection.

    PubMed

    Warfield, Kelly L; Perkins, Jeremy G; Swenson, Dana L; Deal, Emily M; Bosio, Catharine M; Aman, M Javad; Yokoyama, Wayne M; Young, Howard A; Bavari, Sina

    2004-07-19

    Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus protein (VP)40, administered 1-3 d before Ebola virus infection rapidly induced protective immunity. VLP injection enhanced the numbers of natural killer (NK) cells in lymphoid tissues. In contrast to live Ebola virus, VLP treatment of NK cells enhanced cytokine secretion and cytolytic activity against NK-sensitive targets. Unlike wild-type mice, treatment of NK-deficient or -depleted mice with VLPs had no protective effect against Ebola virus infection and NK cells treated with VLPs protected against Ebola virus infection when adoptively transferred to naive mice. The mechanism of NK cell-mediated protection clearly depended on perforin, but not interferon-gamma secretion. Particles containing only VP40 were sufficient to induce NK cell responses and provide protection from infection in the absence of the viral GP. These findings revealed a decisive role for NK cells during lethal Ebola virus infection. This work should open new doors for better understanding of Ebola virus pathogenesis and direct the development of immunotherapeutics, which target the innate immune system, for treatment of Ebola virus infection. PMID:15249592

  12. The role of shrimp miR-965 in virus infection.

    PubMed

    Shu, Le; Li, Changrun; Zhang, Xiaobo

    2016-07-01

    RNAi, mediated by microRNAs (miRNAs), has attracted increasing attention for its important role in cross-talk between host and virus. However, the role of host miRNA in the virus infection in vivo has not been intensively investigated. In this study, the effects of a shrimp miRNA (miR-965) on the white spot syndrome virus (WSSV) infection were characterized. The results indicated that the expression of miR-965 was significantly upregulated in shrimp in response to the WSSV challenge, suggesting its involvement in the virus infection. The miR-965 silencing led to significant increases of WSSV copies and virus-infected shrimp mortality, while the miR-965 overexpression resulted in the decreased WSSV copies and virus-infected shrimp mortality, indicating that miR-965 played a negative role in the WSSV infection. The further data revealed that miR-965 inhibited the virus infection by targeting the viral wsv240 gene, an important gene required for the WSSV infection in shrimp. The results demonstrated that miR-965 could promote the shrimp phagocytosis against virus infection by targeting the shrimp ATG5 (autophagy related 5) gene. Therefore, our findings presented novel evidence to better understand the anfractuous host-virus interactions in vivo. PMID:27134077

  13. Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages

    PubMed Central

    Lietzén, Niina; Julkunen, Ilkka; Aittokallio, Tero; Matikainen, Sampsa; Nyman, Tuula A.

    2011-01-01

    Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X7 receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages. PMID:21589892

  14. Evaluation of monkeypox virus infection of prairie dogs (Cynomys ludovicianus) using in vivo bioluminescent imaging

    USGS Publications Warehouse

    Falendysz, Elizabeth A.; Londoño-Navas, Angela M.; Meteyer, Carol U.; Pussini, Nicola; Lopera, Juan G.; Osorio, Jorge E.; Rocke, Tonie E.

    2014-01-01

    Monkeypox (MPX) is a re-emerging zoonotic disease that is endemic in Central and West Africa, where it can cause a smallpox-like disease in humans. Despite many epidemiologic and field investigations of MPX, no definitive reservoir species has been identified. Using recombinant viruses expressing the firefly luciferase (luc) gene, we previously demonstrated the suitability of in vivo bioluminescent imaging (BLI) to study the pathogenesis of MPX in animal models. Here, we evaluated BLI as a novel approach for tracking MPX virus infection in black-tailed prairie dogs (Cynomys ludovicianus). Prairie dogs were affected during a multistate outbreak of MPX in the US in 2003 and have since been used as an animal model of this disease. Our BLI results were compared with PCR and virus isolation from tissues collected postmortem. Virus was easily detected and quantified in skin and superficial tissues by BLI before and during clinical phases, as well as in subclinical secondary cases, but was not reliably detected in deep tissues such as the lung. Although there are limitations to viral detection in larger wild rodent species, BLI can enhance the use of prairie dogs as an animal model of MPX and can be used for the study of infection, disease progression, and transmission in potential wild rodent reservoirs.

  15. Possible Zika Virus Infection Among Pregnant Women - United States and Territories, May 2016.

    PubMed

    Simeone, Regina M; Shapiro-Mendoza, Carrie K; Meaney-Delman, Dana; Petersen, Emily E; Galang, Romeo R; Oduyebo, Titilope; Rivera-Garcia, Brenda; Valencia-Prado, Miguel; Newsome, Kimberly B; Pérez-Padilla, Janice; Williams, Tonya R; Biggerstaff, Matthew; Jamieson, Denise J; Honein, Margaret A

    2016-01-01

    Zika virus is a cause of microcephaly and brain abnormalities (1), and it is the first known mosquito-borne infection to cause congenital anomalies in humans. The establishment of a comprehensive surveillance system to monitor pregnant women with Zika virus infection will provide data to further elucidate the full range of potential outcomes for fetuses and infants of mothers with asymptomatic and symptomatic Zika virus infection during pregnancy. In February 2016, Zika virus disease and congenital Zika virus infections became nationally notifiable conditions in the United States (2). Cases in pregnant women with laboratory evidence of Zika virus infection who have either 1) symptomatic infection or 2) asymptomatic infection with diagnosed complications of pregnancy can be reported as cases of Zika virus disease to ArboNET* (2), CDC's national arboviral diseases surveillance system. Under existing interim guidelines from the Council for State and Territorial Epidemiologists (CSTE), asymptomatic Zika virus infections in pregnant women who do not have known pregnancy complications are not reportable. ArboNET does not currently include pregnancy surveillance information (e.g., gestational age or pregnancy exposures) or pregnancy outcomes. To understand the full impact of infection on the fetus and neonate, other systems are needed for reporting and active monitoring of pregnant women with laboratory evidence of possible Zika virus infection during pregnancy. Thus, in collaboration with state, local, tribal, and territorial health departments, CDC established two surveillance systems to monitor pregnancies and congenital outcomes among women with laboratory evidence of Zika virus infection(†) in the United States and territories: 1) the U.S. Zika Pregnancy Registry (USZPR),(§) which monitors pregnant women residing in U.S. states and all U.S. territories except Puerto Rico, and 2) the Zika Active Pregnancy Surveillance System (ZAPSS), which monitors pregnant women

  16. Isolation and characterization of a new strain of lymphocytic choriomeningitis virus from rodents in southwestern France.

    PubMed

    Yama, Ines N; Cazaux, Benoite; Britton-Davidian, Janice; Moureau, Grégory; Thirion, Laurence; de Lamballerie, Xavier; Dobigny, Gauthier; Charrel, Rémi N

    2012-10-01

    A total of 821 tissue samples from rodents trapped during field campaigns organized in Europe and Africa were screened for the presence of arenaviruses by molecular methods and cell culture inoculation when feasible. Two Mus musculus domesticus trapped in the southwestern part of France were infected with a potentially new strain of lymphocytic choriomeningitis virus (LCMV), here referred to as LCMV strain HP65-2009, which was isolated and genetically characterized by whole genome sequencing. Genetic and phylogenetic analyses comparing LCMV HP65-2009 with 26 other LCMV strains showed that it represents a novel highly-divergent strain within the group of Mus musculus-associated LCMV. PMID:22651393

  17. Impact of dengue virus infection and its control.

    PubMed

    Igarashi, A

    1997-08-01

    Dengue virus infection has been counted among emerging and re-emerging diseases because of (1) the increasing number of patients, (2) the expansion of epidemic areas, and (3) the appearance of severe clinical manifestation of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS), which is often fatal if not properly treated. In the meantime, there are no effective dengue control measures: a dengue vaccine is still under development and vector control does not provide a long-lasting effect. In order to obtain direct evidence for the virulent virus theory concerning the pathogenesis of DHF/DSS, type 2 dengue virus strains isolated from patients with different clinical severities in the same epidemic area in northeast Thailand, during the same season, were comparatively sequenced. The result revealed a DF strain specific amino acid substitution from I to R in the PrM, and a DSS strain specific amino acid substitution from D to G in the NS1 gene regions, which could significantly alter the nature of these proteins. Moreover, DF strain specific nucleotide substitutions in the 3' noncoding region were predicted to alter its secondary structure. These amino acid and nucleotide substitutions in other strains isolated in different epidemic areas during other seasons, together with their biological significance, remain to be confirmed. In order to innovate dengue vector control, field tests were carried out in dengue epidemic areas in Vietnam to examine the efficacy of Olyset Net screen, which is a wide-mesh net made of polyethylene thread impregnated with permethrin. The results show that Olyset Net (1) reduced the number of principal dengue vector species, Aedes aegypti, (2) interrupted the silent transmission of dengue viruses and (3) was highly appreciated by the local people as a convenient and comfortable vector control method. This encouraging evaluation of the Olyset Net screen should be confirmed further by other tests under different settings. PMID:9348165

  18. Clinical aspects on Epstein-Barr virus infection.

    PubMed

    Andersson, J P

    1991-01-01

    Epstein-Barr virus infection (EBV) was discovered 25 years ago in tumour cells from Burkitt's lymphoma. Extensive virological studies have relieved that EBV causes infectious mononucleosis and contributes to the pathogenesis of Burkitt's lymphoma and nasopharyngeal cancer. Atypical courses of the primary infection may induce meningoencephalitis or hepatitis and are attracting increasing attention. Antiviral treatment with acyclovir has been administered for 7 days, intravenously or orally, in the early stages of infectious mononucleosis, in 2 placebo controlled trials. An inhibition of oropharyngeal EBV replication was verified but minimal effects on clinical symptoms was observed. A combination of intravenous acyclovir and prednisolone treatment for 10 days was therefore tried in 15 patients with fulminant mononucleosis in a pilot study. A transient cessation of virus shedding was noticed in all patients, and a substantial clinical effect on pharyngeal symptoms and on fever was seen in 12/15 patients within 3 days. Treatment with chemotherapy or irradiation is recommended in EBV-associated B-cell lymphomas seen in immunosuppressed, transplanted, or human immunodeficiency virus-seropositive patients. No effect of acyclovir has been reported, but such therapy may be considered in the early stage when EBV induces a polyclonal B cell activation. Acyclovir treatment is effective in the EBV-genome positive hairy leukoplakia noticed in human immunodeficiency virus-seropositive patients. However, no effect of any antiviral therapy has been reported in the X-linked lymphoproliferative syndrome affecting in particular 2-7 year old boys. Prophylactic use of immunoglobulin or acyclovir has been suggested in susceptible children. These results indicate that the variety of clinical manifestations induced by EBV at least partly depend on the immune response elicited in the host and not of virus replication per se. Therefore, treatment of these various disorders cannot be

  19. Influenza A virus infections in marine mammals and terrestrial carnivores.

    PubMed

    Harder, Timm C; Siebert, Ursula; Wohlsein, Peter; Vahlenkamp, Thomas

    2013-01-01

    Influenza A viruses (IAV), members of the Orthomyxoviridae, cover a wide host spectrum comprising a plethora of avian and, in comparison, a few mammalian species. The viral reservoir and gene pool are kept in metapopulations of aquatic wild birds. The mammalian-adapted IAVs originally arose by transspecies transmission from avian sources. In swine, horse and man, species-adapted IAV lineages circulate independently of the avian reservoir and cause predominantly respiratory disease of highly variable severity. Sporadic outbreaks of IAV infections associated with pneumonic clinical signs have repeatedly occurred in marine mammals (harbour seals [Phoca vitulina]) off the New England coast of the U.S.A. due to episodic transmission of avian IAV. However, no indigenous marine mammal IAV lineages are described. In contrast to marine mammals, avian- and equine-derived IAVs have formed stable circulating lineages in terrestrial carnivores: IAVs of subtype H3N2 and H3N8 are found in canine populations in South Korea, China, and the U.S.A. Experimental infections revealed that dogs and cats can be infected with an even wider range of avian IAVs. Cats, in particular, also proved susceptible to native infection with human pandemic H1N1 viruses and, according to serological data, may be vulnerable to infection with further human-adapted IAVs. Ferrets are susceptible to a variety of avian and mammalian IAVs and are an established animal model of human IAV infection. Thus, a potential role of pet cats, dogs and ferrets as mediators of avian-derived viruses to the human population does exist. A closer observation for influenza virus infections and transmissions at this animal-human interface is indicated. PMID:24511825

  20. PRRSV receptors and their roles in virus infection.

    PubMed

    Shi, Chongxu; Liu, Yali; Ding, Yaozhong; Zhang, Yongguang; Zhang, Jie

    2015-05-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) has a restricted cell tropism and prefers to invade well-differentiated cells of the monocyte/macrophage lineage, such as pulmonary alveolar macrophages and African green monkey kidney cell line MA-104 and its derivatives, such as Marc-145, Vero and CL-2621. PRRSV infection of the host cells actually is a receptor-mediated endocytosis and replication process. The presence and absence of the cellular receptors decide whether the cell lines are permissive or non-permissive to PRRSV infection. Several PRRSV non-permissive cell lines, such as BHK-21, PK-15 and CHO-K1, have been shown to become sensitive to the virus infection upon expression of the recombinant receptor proteins. Up to now, heparin sulfate, sialoadhesin, CD163, CD151 and vimentin have been identified as the important PRRSV receptors via their involvement in virus attachment, internalization or uncoating. Each receptor is characterized by the distribution in different cells, the function in virus different infection stages and the interaction model with the viral proteins or genes. Joint forces of the receptors recently attract attentions due to the specific function. PRRSV receptors have become the targets for designing the new anti-viral reagents or the recombinant cell lines used for isolating the viruses or developing more effective vaccines due to their more conserved sequences compared with the genetic variation of the virus. In this paper, the role of PRRSV receptors and the molecular mechanism of the interaction between the virus and the receptors are reviewed. PMID:25666932

  1. Active NF-kappaB signalling is a prerequisite for influenza virus infection.

    PubMed

    Nimmerjahn, Falk; Dudziak, Diana; Dirmeier, Ulrike; Hobom, Gerd; Riedel, Alexander; Schlee, Martin; Staudt, Louis M; Rosenwald, Andreas; Behrends, Uta; Bornkamm, Georg W; Mautner, Josef

    2004-08-01

    Influenza virus still poses a major threat to human health. Despite widespread vaccination programmes and the development of drugs targeting essential viral proteins, the extremely high mutation rate of influenza virus still leads to the emergence of new pathogenic virus strains. Therefore, it has been suggested that cellular cofactors that are essential for influenza virus infection might be better targets for antiviral therapy. It has previously been reported that influenza virus efficiently infects Epstein-Barr virus-immortalized B cells, whereas Burkitt's lymphoma cells are virtually resistant to infection. Using this cellular system, it has been shown here that an active NF-kappaB signalling pathway is a general prerequisite for influenza virus infection of human cells. Cells with low NF-kappaB activity were resistant to influenza virus infection, but became susceptible upon activation of NF-kappaB. In addition, blocking of NF-kappaB activation severely impaired influenza virus infection of otherwise highly susceptible cells, including the human lung carcinoma cell lines A549 and U1752 and primary human cells. On the other hand, infection with vaccinia virus was not dependent on an active NF-kappaB signalling pathway, demonstrating the specificity of this pathway for influenza virus infection. These results might be of major importance for both the development of new antiviral therapies and the understanding of influenza virus biology. PMID:15269376

  2. Transcriptional Profiling of the Immune Response to Marburg Virus Infection

    PubMed Central

    Yen, Judy; Caballero, Ignacio S.; Garamszegi, Sara; Malhotra, Shikha; Lin, Kenny; Hensley, Lisa; Goff, Arthur J.

    2015-01-01

    ABSTRACT Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. IMPORTANCE Marburg virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the

  3. Callithrix penicillata: a feasible experimental model for dengue virus infection.

    PubMed

    Ferreira, Milene Silveira; de Castro, Paulo Henrique Gomes; Silva, Gilmara Abreu; Casseb, Samir Mansur Moraes; Dias Júnior, Antônio Gregório; Rodrigues, Sueli Guerreiros; Azevedo, Raimunda do Socorro da Silva; Costa e Silva, Matheus Fernandes; Zauli, Danielle Alves Gomes; Araújo, Márcio Sobreira Silva; Béla, Samantha Ribeiro; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Vasconcelos, Pedro Fernando da Costa

    2014-01-01

    , a protective axes TNF-alpha/Lymphocytes/Platelets, and a pathological IL-2/IL-6/Viremia/Monocyte/PT bond. Later on, the biomarker network highlighted the interaction IFN-gamma/PLT/DENV-3(IgM;HAI)/PT, and the involvement of type-2 cytokines (IL-4; IL-5). Our findings demonstrated that C. penicillata is a feasible experimental model for dengue virus infection, which could be useful to pathogenesis studies, discovery of novel antiviral drugs as well as to evaluate vaccine candidates against DENV. PMID:24361035

  4. Factors predicting kidney damage in Puumala virus infected patients in Southern Denmark.

    PubMed

    Skarphedinsson, S; Thiesson, H C; Shakar, S A; Tepel, M

    2015-10-01

    In Europe, infections with Puumala hantavirus cause nephropathia epidemica. Presently the risk factors predicting severe kidney damage after Puumala virus infection are not well known. The objective of the study was to investigate environmental and individual factors predicting severe kidney damage caused by serologically established Puumala infections. In a nationwide cohort study we investigated all serologically established Puumala infections in Southern Denmark from 1996 to 2012. A total of 184 patients had serologically verified Puumala virus infection. In patients with Puumala virus infections the decrease of platelet counts preceded acute kidney failure. Multivariable logistic regression demonstrated that recent activities in the forest, platelet counts, and flu-like symptoms predicted estimated glomerular filtration rates less than 30 mL/min/1.73 m(²), but not age, gender, fever, nor abdominal pain. Severe kidney damage in Puumala infections in Southern Denmark is associated with the risk of recent activities in the forest. PMID:26205664

  5. Hunting in the Rainforest and Mayaro Virus Infection: An emerging Alphavirus in Ecuador

    PubMed Central

    Izurieta, Ricardo O; Macaluso, Maurizio; Watts, Douglas M; Tesh, Robert B; Guerra, Bolivar; Cruz, Ligia M; Galwankar, Sagar; Vermund, Sten H

    2011-01-01

    Objectives: The objectives of this report were to document the potential presence of Mayaro virus infection in Ecuador and to examine potential risk factors for Mayaro virus infection among the personnel of a military garrison in the Amazonian rainforest. Materials and Methods: The study population consisted of the personnel of a garrison located in the Ecuadorian Amazonian rainforest. The cross-sectional study employed interviews and seroepidemiological methods. Humoral immune response to Mayaro virus infection was assessed by evaluating IgM- and IgG-specific antibodies using ELISA. Results: Of 338 subjects studied, 174 were from the Coastal zone of Ecuador, 73 from Andean zone, and 91 were native to the Amazonian rainforest. Seroprevalence of Mayaro virus infection was more than 20 times higher among Amazonian natives (46%) than among subjects born in other areas (2%). Conclusions: Age and hunting in the rainforest were significant predictors of Mayaro virus infection overall and among Amazonian natives. The results provide the first demonstration of the potential presence of Mayaro virus infection in Ecuador and a systematic evaluation of risk factors for the transmission of this alphavirus. The large difference in prevalence rates between Amazonian natives and other groups and between older and younger natives suggest that Mayaro virus is endemic and enzootic in the rainforest, with sporadic outbreaks that determine differences in risk between birth cohorts of natives. Deep forest hunting may selectively expose native men, descendants of the Shuar and Huaronai ethnic groups, to the arthropod vectors of Mayaro virus in areas close to primate reservoirs. PMID:22223990

  6. Noninvasive and label-free determination of virus infected cells by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Moor, Kamila; Ohtani, Kiyoshi; Myrzakozha, Diyas; Zhanserkenova, Orik; Andriana, Bibin. B.; Sato, Hidetoshi

    2014-06-01

    The present study demonstrates that Raman spectroscopy is a powerful tool for the detection of virus-infected cells. Adenovirus infection of human embryonic kidney 293 cells was successfully detected at 12, 24, and 48 h after initiating the infection. The score plot of principal component analysis discriminated the spectra of the infected cells from those of the control cells. The viral infection was confirmed by the conventional immunostaining method performed 24 h after the infection. The newly developed method provides a fast and label-free means for the detection of virus-infected cells.

  7. Clinical and biological differences between recurrent herpes simplex virus and varicella-zoster virus infections

    SciTech Connect

    Straus, S.E. )

    1989-12-01

    The major features that distinguish recurrent herpes simplex virus infections from zoster are illustrated in this article by two case histories. The clinical and epidemiologic features that characterize recurrent herpes simplex virus and varicella-zoster virus infections are reviewed. It is noted that herpesvirus infections are more common and severe in patients with cellular immune deficiency. Each virus evokes both humoral and cellular immune response in the course of primary infection. DNA hybridization studies with RNA probes labelled with sulfur-35 indicate that herpes simplex viruses persist within neurons, and that varicella-zoster virus is found in the satellite cells that encircle the neurons.

  8. Bilateral optic neuritis in a child following Epstein-Barr virus infection.

    PubMed

    Pahor, Dusica

    2005-01-01

    A rare case of bilateral optic neuritis is presented in a child with no light perception. Ophthalmic examination revealed dilated pupils without reaction to the light, swollen optic discs with small peripapillary hemorrhages in both eyes. Serology revealed evidence of recent Epstein-Barr virus infection. After treatment with high dose of corticosteroid visual acuity gradually improved. After four months visual acuity was normal despite complete pallor of the optic disc. Ebstein-Barr virus infection should be considered in the differential diagnosis of bilateral optic neuritis in a child with severe bilateral visual loss. PMID:16193695

  9. Predicted pattern of Zika virus infection distribution with reference to rainfall in Thailand.

    PubMed

    Wiwanitkit, Somsri; Wiwanitkit, Viroj

    2016-07-01

    Zika virus infection is the present global medical problem. The disease appears in several countries around the world. The relationship between rainfall and occurrence of Zika virus infection was previously mentioned. Here, the authors use the mathematical modeling technique to reappraise on the previous data on immunoreactivity rate of Zika virus, dengue virus and Ckikungunya virus in Thailand and the reported interrelationship between arboviral infections and rainfall in Thailand for constructing of the predicted pattern of Zika virus distribution in Thailand. This data can be a useful tool for further disease surveillance in this area. PMID:27393105

  10. Pathology of experimental Machupo virus infection, Chicava strain, in cynomolgus macaques (Macaca fascicularis) by intramuscular and aerosol exposure.

    PubMed

    Bell, T M; Shaia, C I; Bunton, T E; Robinson, C G; Wilkinson, E R; Hensley, L E; Cashman, K A

    2015-01-01

    Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection. PMID:24990481

  11. Lymphocytic Choriomeningitis Virus in Employees and Mice at Multipremises Feeder-Rodent Operation, United States, 2012

    PubMed Central

    Ströher, Ute; Edison, Laura; Albariño, César G.; Lovejoy, Jodi; Armeanu, Emilian; House, Jennifer; Cory, Denise; Horton, Clayton; Fowler, Kathy L.; Austin, Jessica; Poe, John; Humbaugh, Kraig E.; Guerrero, Lisa; Campbell, Shelley; Gibbons, Aridth; Reed, Zachary; Cannon, Deborah; Manning, Craig; Petersen, Brett; Metcalf, Douglas; Marsh, Bret; Nichol, Stuart T.; Rollin, Pierre E.

    2014-01-01

    We investigated the extent of lymphocytic choriomeningitis virus (LCMV) infection in employees and rodents at 3 commercial breeding facilities. Of 97 employees tested, 31 (32%) had IgM and/or IgG to LCMV, and aseptic meningitis was diagnosed in 4 employees. Of 1,820 rodents tested in 1 facility, 382 (21%) mice (Mus musculus) had detectable IgG, and 13 (0.7%) were positive by reverse transcription PCR; LCMV was isolated from 8. Rats (Rattus norvegicus) were not found to be infected. S-segment RNA sequence was similar to strains previously isolated in North America. Contact by wild mice with colony mice was the likely source for LCMV, and shipments of infected mice among facilities spread the infection. The breeding colonies were depopulated to prevent further human infections. Future outbreaks can be prevented with monitoring and management, and employees should be made aware of LCMV risks and prevention. PMID:24447605

  12. The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles

    PubMed Central

    Ziegler, Christopher M.; Eisenhauer, Philip; Bruce, Emily A.; Weir, Marion E.; King, Benjamin R.; Klaus, Joseph P.; Krementsov, Dimitry N.; Shirley, David J.; Ballif, Bryan A.; Botten, Jason

    2016-01-01

    Arenaviruses cause severe diseases in humans but establish asymptomatic, lifelong infections in rodent reservoirs. Persistently-infected rodents harbor high levels of defective interfering (DI) particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect. Little is known about what drives the production of DI particles. We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. In contrast, DI particle release critically requires the PPXY late domain and is ESCRT-dependent. Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation. Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation. PMID:27010636

  13. Virus infection mediates the effects of elevated CO2 on plants and vectors.

    PubMed

    Trębicki, Piotr; Vandegeer, Rebecca K; Bosque-Pérez, Nilsa A; Powell, Kevin S; Dader, Beatriz; Freeman, Angela J; Yen, Alan L; Fitzgerald, Glenn J; Luck, Jo E

    2016-01-01

    Atmospheric carbon dioxide (CO2) concentration has increased significantly and is projected to double by 2100. To increase current food production levels, understanding how pests and diseases respond to future climate driven by increasing CO2 is imperative. We investigated the effects of elevated CO2 (eCO2) on the interactions among wheat (cv. Yitpi), Barley yellow dwarf virus and an important pest and virus vector, the bird cherry-oat aphid (Rhopalosiphum padi), by examining aphid life history, feeding behavior and plant physiology and biochemistry. Our results showed for the first time that virus infection can mediate effects of eCO2 on plants and pathogen vectors. Changes in plant N concentration influenced aphid life history and behavior, and N concentration was affected by virus infection under eCO2. We observed a reduction in aphid population size and increased feeding damage on noninfected plants under eCO2 but no changes to population and feeding on virus-infected plants irrespective of CO2 treatment. We expect potentially lower future aphid populations on noninfected plants but no change or increased aphid populations on virus-infected plants therefore subsequent virus spread. Our findings underscore the complexity of interactions between plants, insects and viruses under future climate with implications for plant disease epidemiology and crop production. PMID:26941044

  14. Non-coding RNAs and heme oxygenase-1 in vaccinia virus infection

    SciTech Connect

    Meseda, Clement A.; Srinivasan, Kumar; Wise, Jasen; Catalano, Jennifer; Yamada, Kenneth M.; Dhawan, Subhash

    2014-11-07

    Highlights: • Heme oxygenase-1 (HO-1) induction inhibited vaccinia virus infection of macrophages. • Reduced infectivity inversely correlated with increased expression of non-coding RNAs. • The regulation of HO-1 and ncRNAs suggests a novel host defense response against vaccinia virus infection. - Abstract: Small nuclear RNAs (snRNAs) are <200 nucleotide non-coding uridylate-rich RNAs. Although the functions of many snRNAs remain undetermined, a population of snRNAs is produced during the early phase of infection of cells by vaccinia virus. In the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (HO-1), suppression of selective snRNA expression, and inhibition of vaccinia virus infection of macrophages. Hemin induced HO-1 expression, completely reversed virus-induced host snRNA expression, and suppressed vaccinia virus infection. This involvement of specific virus-induced snRNAs and associated gene clusters suggests a novel HO-1-dependent host-defense pathway in poxvirus infection.

  15. Vasculitis as a Presenting Manifestation of Chronic Hepatitis B Virus Infection: A Case Report

    PubMed Central

    Singh, Harpreet; Sukhija, Gagandeep; Kaur, Parminder; Govil, Nikhil

    2016-01-01

    Hepatitis B virus is responsible for causing hepatic complications like acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma along with some uncommon immune mediated extrahepatic manifestations. Vasculitis remains an uncommon extrahepatic complication of hepatitis B virus infection. Herein we report a case of hepatitis B infection that presented with leucocytoclastic vasculitis as an initial manifestation and managed successfully with entacavir therapy. PMID:27042512

  16. Intraoral herpes simplex virus infection in a patient with common variable immunodeficiency.

    PubMed

    Villa, Alessandro; Treister, Nathaniel S

    2013-10-01

    We report a challenging case of an atypical presentation of recrudescent herpes simplex virus infection in a patient with common variable immunodeficiency. Oral infections in immunosuppressed patients may present with unusual clinical features that can mimic non-infectious diseases. This report discusses the diagnostic steps necessary for definitive diagnosis and to guide appropriate and effective management. PMID:23933299

  17. Virus infection mediates the effects of elevated CO2 on plants and vectors

    NASA Astrophysics Data System (ADS)

    Trębicki, Piotr; Vandegeer, Rebecca K.; Bosque-Pérez, Nilsa A.; Powell, Kevin S.; Dader, Beatriz; Freeman, Angela J.; Yen, Alan L.; Fitzgerald, Glenn J.; Luck, Jo E.

    2016-03-01

    Atmospheric carbon dioxide (CO2) concentration has increased significantly and is projected to double by 2100. To increase current food production levels, understanding how pests and diseases respond to future climate driven by increasing CO2 is imperative. We investigated the effects of elevated CO2 (eCO2) on the interactions among wheat (cv. Yitpi), Barley yellow dwarf virus and an important pest and virus vector, the bird cherry-oat aphid (Rhopalosiphum padi), by examining aphid life history, feeding behavior and plant physiology and biochemistry. Our results showed for the first time that virus infection can mediate effects of eCO2 on plants and pathogen vectors. Changes in plant N concentration influenced aphid life history and behavior, and N concentration was affected by virus infection under eCO2. We observed a reduction in aphid population size and increased feeding damage on noninfected plants under eCO2 but no changes to population and feeding on virus-infected plants irrespective of CO2 treatment. We expect potentially lower future aphid populations on noninfected plants but no change or increased aphid populations on virus-infected plants therefore subsequent virus spread. Our findings underscore the complexity of interactions between plants, insects and viruses under future climate with implications for plant disease epidemiology and crop production.

  18. Virus infection mediates the effects of elevated CO2 on plants and vectors

    PubMed Central

    Trębicki, Piotr; Vandegeer, Rebecca K.; Bosque-Pérez, Nilsa A.; Powell, Kevin S.; Dader, Beatriz; Freeman, Angela J.; Yen, Alan L.; Fitzgerald, Glenn J.; Luck, Jo E.

    2016-01-01

    Atmospheric carbon dioxide (CO2) concentration has increased significantly and is projected to double by 2100. To increase current food production levels, understanding how pests and diseases respond to future climate driven by increasing CO2 is imperative. We investigated the effects of elevated CO2 (eCO2) on the interactions among wheat (cv. Yitpi), Barley yellow dwarf virus and an important pest and virus vector, the bird cherry-oat aphid (Rhopalosiphum padi), by examining aphid life history, feeding behavior and plant physiology and biochemistry. Our results showed for the first time that virus infection can mediate effects of eCO2 on plants and pathogen vectors. Changes in plant N concentration influenced aphid life history and behavior, and N concentration was affected by virus infection under eCO2. We observed a reduction in aphid population size and increased feeding damage on noninfected plants under eCO2 but no changes to population and feeding on virus-infected plants irrespective of CO2 treatment. We expect potentially lower future aphid populations on noninfected plants but no change or increased aphid populations on virus-infected plants therefore subsequent virus spread. Our findings underscore the complexity of interactions between plants, insects and viruses under future climate with implications for plant disease epidemiology and crop production. PMID:26941044

  19. Virus Infection and Titration of SARS-CoV in Mouse Lung

    PubMed Central

    Fett, Craig; Zhao, Jincun; Perlman, Stanley

    2016-01-01

    Two critical steps when investigating an animal model of a virus infection are consistently successfully infecting animals and accurately determining viral titers in tissue throughout the course of infection. Here we discuss in detail how to infect mice with SARS-CoV and then quantify the titer of virus in the lung.

  20. MiRNA expression signatures induced by Marek disease virus infection in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    MMicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression at the post-transcriptional level. Emerging evidence suggests that differential miRNA expression is associated with viral infection and cancer. Marek's disease virus infection induces lymphoma in chickens. However, the host...

  1. Syphilis? An Unusual Cause of Surgical Emergency in a Human Immunodeficiency Virus-Infected Man

    PubMed Central

    Bender Ignacio, Rachel A.; Koch, Lisa L.; Dhanireddy, Shireesha; Charmie Godornes, B.; Lukehart, Sheila A.; Marrazzo, Jeanne M.

    2015-01-01

    We report on a human immunodeficiency virus-infected man undergoing urgent anorectal surgery, with multi-centimeter fungating masses discovered inside the anus. Initial pathology was inconclusive. After the patient developed a disseminated rash postoperatively determined to be secondary syphilis, the anorectal pathology was reviewed and Treponema pallidum DNA was amplified by polymerase chain reaction from the mass. PMID:26213693

  2. Association Between Antibody Titers and Protection Against Influenza Virus Infection Within Households

    PubMed Central

    Tsang, Tim K.; Cauchemez, Simon; Perera, Ranawaka A. P. M.; Freeman, Guy; Fang, Vicky J.; Ip, Dennis K. M.; Leung, Gabriel M.; Malik Peiris, Joseph Sriyal; Cowling, Benjamin J.

    2014-01-01

    Background. Previous studies have established that antibody titer measured by the hemagglutination-inhibiting (HAI) assay is correlated with protection against influenza virus infection, with an HAI titer of 1:40 generally associated with 50% protection. Methods. We recruited index cases with confirmed influenza virus infection from outpatient clinics, and followed up their household contacts for 7–10 days to identify secondary infections. Serum samples collected from a subset of household contacts were tested by HAI and microneutralization (MN) assays against prevalent influenza viruses. We analyzed the data using an individual hazard-based transmission model that adjusted for age and vaccination history. Results. Compared to a reference group with antibody titers <1:10, we found that HAI titers of 1:40 against influenza A(H1N1) and A(H3N2) were associated with 31% (95% confidence interval [CI], 13%–46%) and 31% (CI, 1%–53%) protection against polymerase chain reaction (PCR)–confirmed A(H1N1) and A(H3N2) virus infection, respectively, while an MN titer of 1:40 against A(H3N2) was associated with 49% (95% CI, 7%–81%) protection against PCR-confirmed A(H3N2) virus infection. Conclusions. An HAI titer of 1:40 was associated with substantially less than 50% protection against PCR-confirmed influenza virus infection within households, perhaps because of exposures of greater duration or intensity in that confined setting. PMID:24676208

  3. Variation Between Strains of Hamsters in the Lethality of Pichinde Virus Infections

    PubMed Central

    Buchmeier, Michael J.; Rawls, William E.

    1977-01-01

    Infection by Pichinde virus, a member of the arenavirus group, was studied in Golden Syrian hamsters (Mesocricetus auratus) with regard to possible mechanisms of resistance to virus infection in adult hamsters. Two hamster strains were found to differ in their susceptibility to lethal Pichinde virus infection. LVG/Lak randomly bred hamsters were found to be 100% susceptible to low doses of Pichinde virus during the first 6 days of life, but after 8 days of life, mortality was uncommon. Peak virus titers in the serum of animals infected at 3 days of life were 4 logs greater than in animals infected at 12 days. MHA/Lak inbred hamsters, in contrast, were found to be susceptible to lethal virus infection both as newborns and as adults. Peak virus titers of greater than 108 plaque-forming units/ml were observed in serum 8 days after infection of adult MHA hamsters as compared with less than 103 plaque-forming units/ml in the serum of adult LVG hamsters. Cultured primary kidney cells and peritoneal macrophages from either hamster strain supported Pichinde virus replication equally well in vitro. Antibodies to the complement-fixing antigens and to antigens at the surface of virus-infected cells were produced by both strains of hamsters. Cyclophosphamide immunosuppression rendered adult LVG animals susceptible to lethal infections, and virus grew to high titers in the treated animals. These findings suggest that immunological factors that appear early in life in LVG hamsters and are deficient in MHA hamsters limit Pichinde virus infection. Unlike previously reported arenavirus diseases, the observations suggest that death is produced by a direct viral effect and not through immunopathological mechanisms. PMID:193786

  4. Outbreak of Chikungunya Virus Infection, Vanimo, Papua New Guinea

    PubMed Central

    Reimer, Lisa J.; Dagina, Rosheila; Susapu, Melinda; Bande, Grace; Katusele, Michelle; Koimbu, Gussy; Jimmy, Stella; Ropa, Berry; Siba, Peter M.; Pavlin, Boris I.

    2013-01-01

    In June 2012, health authorities in Papua New Guinea detected an increase in febrile illnesses in Vanimo. Chikungunya virus of the Eastern/Central/Southern African genotype harboring the E1:A226V mutation was identified. This ongoing outbreak has spread to ≥8 other provinces and has had a harmful effect on public health. PMID:23965757

  5. Patterns of Multi-Virus Infections in Florida Watermelon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The whitefly-transmitted viruses Squash vein yellowing virus (SqVYV) and Cucurbit leaf crumple virus (CuLCrV) have had serious impact on watermelon production in west-central and southwest Florida in recent years. We collected plants randomly from a commercial watermelon field in southwest Florida s...

  6. Immunobiology of cytotoxic T-cell escape mutants of lymphocytic choriomeningitis virus.

    PubMed Central

    Moskophidis, D; Zinkernagel, R M

    1995-01-01

    Infection with virus variants exhibiting changes in the peptide sequences defining immunodominant determinants that abolish recognition by antiviral cytotoxic T cells (CTL) presents a considerable challenge to the antiviral T-cell immune system and may enable some viruses to persist in hosts. The potential importance of such variants with respect to mechanisms of viral persistence and disease pathogenesis was assessed by infecting adult mice with variants of lymphocytic choriomeningitis virus (LCMV) strain WE. These variants were selected in vivo or in vitro for resistance to lysis by CD8+ H-2b-restricted antiviral CTL. The majority of anti-LCMV CTL in infected H-2b mice recognize epitopes defined by residues 32 to 42 and 275 to 289 (epitopes 32-42 and 275-289) of the LCMV glycoprotein or 397 to 407 of the viral nucleoprotein. The 8.7 variant exhibits a change in the epitope 32-42 (Val-35-->Leu), and variant CL1.2 exhibits a change in the epitope 275-289 (Asn-280-->Asp) of the wild-type LCMV-WE. The double-mutated 8.7-B23 variant had the variation of 8.7 and an additional change located in the epitope 275-289 (Asn-280-->Ser). The 8.7 variant peptide with unchanged anchor positions bound efficiently to H-2Db and H-2Kb molecules but induced only a very weak CTL response. CTL epitope 275-289 of CL1.2 and 8.7-B23 altered at predicted anchor residues were unable to bind Db molecules and were also not recognized by antiviral CTL. Infection of C57BL/6 mice (H-2b) with the variants exhibiting mutations of one of the CTL epitopes, i.e., 8.7 or CL1.2, induced CTL responses specific for the unmutated epitopes comparable with those induced by infection with WE, and these responses were sufficient to eliminate virus from the host. In contrast, infection with the double-mutated variant 8.7-B23 induced CTL activity that was reduced by a factor of about 50-fold compared with wild-type LCMV. Consequently, high doses (10(7) PFU intravenously) of this virus were eliminated slowly and

  7. Evaluation of chikungunya virus infection in children from India during 2009-2010: A cross sectional observational study.

    PubMed

    Raghavendhar, B Siva; Ray, Pratima; Ratagiri, Vinod H; Sharma, B S; Kabra, Sushil K; Lodha, Rakesh

    2016-06-01

    . Maximum positive cases were from KIMS center, Hubli. Seasonally, positivity varied with number of enrolled cases at KIMS and SMS. Joint pain was significantly associated with CHIKV positivity (P = 0.0156). Presence/absence of certain clinical features varied with age (P < 0.05). Sequence analysis revealed four amino acid changes. Phylogenetic analysis with partial sequences of E1 gene from KIMS (n = 12) and SMS (n = 5) showed that the study isolates clustered with Indian Ocean Lineage strains (IOL) of East, Central and South African (ECSA) type. Evaluation of chikungunya virus infection in children from India during 2009-2010 showed high proportion of CHIKV infection in Southern region of India compared to Northern region. The circulating CHIKV strains were of Indian Ocean Lineage (IOL) group within the East, Central, and South African (ECSA) genotype. However few amino acid changes were observed in E1 polypeptide with reference to African strain S-27 (AF369024). Further studies are needed to know the implications of these changes in vector-pathogen compatibility and host-pathogen interactivity. As a whole, this study highlighted the proportion of CHIKV cases, lineage of causative strain and evolutionary pattern of circulating strain in terms of amino acid changes in the structural protein. J. Med. Virol. 88:923-930, 2016. © 2015 Wiley Periodicals, Inc. PMID:26581026

  8. Pancreatitis and cholecystitis in primary acute symptomatic Epstein-Barr virus infection - Systematic review of the literature.

    PubMed

    Kottanattu, Lisa; Lava, Sebastiano A G; Helbling, Rossana; Simonetti, Giacomo D; Bianchetti, Mario G; Milani, Gregorio P

    2016-09-01

    Acute pancreatitis and acalculous cholecystitis have been occasionally reported in primary acute symptomatic Epstein-Barr virus infection. We completed a review of the literature and retained 48 scientific reports published between 1966 and 2016 for the final analysis. Acute pancreatitis was recognized in 14 and acalculous cholecystitis in 37 patients with primary acute symptomatic Epstein-Barr virus infection. In all patients, the features of acute pancreatitis or acalculous cholecystitis concurrently developed with those of primary acute symptomatic Epstein-Barr virus infection. Acute pancreatitis and acalculous cholecystitis resolved following a hospital stay of 25days or less. Acalculous cholecystitis was associated with Gilbert-Meulengracht syndrome in two cases. In conclusion, this thorough analysis indicates that acute pancreatitis and acalculous cholecystitis are unusual but plausible complications of primary acute symptomatic Epstein-Barr virus infection. Pancreatitis and cholecystitis deserve consideration in cases with severe abdominal pain. These complications are usually rather mild and resolve spontaneously without sequelae. PMID:27434148

  9. Imported zika virus infection from the cook islands into australia, 2014.

    PubMed

    Pyke, Alyssa T; Daly, Michelle T; Cameron, Jane N; Moore, Peter R; Taylor, Carmel T; Hewitson, Glen R; Humphreys, Jan L; Gair, Richard

    2014-01-01

    A female resident of Townsville, Queensland, Australia has been diagnosed with Zika virus infection following a recent trip to the Cook Islands. An initial serum sample collected in March, 2014 was positive by two separate Zika virus TaqMan real-time RT-PCRs and a pan-Flavivirus RT-PCR. Nucleotide sequencing and phylogenetics of the complete Cook Islands Zika virus envelope gene revealed 99.1% homology with a previous Cambodia 2010 sequence within the Asian lineage. In addition, IgG and IgM antibody seroconversions were detected between paired acute and convalescent phase sera using recombinant Zika virus serology assays. This is the first known imported case of Zika virus infection into northern Queensland where the potential mosquito vector Aedes aegypti is present and only the second such reported case diagnosed within Australia. PMID:24944843

  10. Dengue Virus Infection of Mast Cells Triggers Endothelial Cell Activation ▿

    PubMed Central

    Brown, Michael G.; Hermann, Laura L.; Issekutz, Andrew C.; Marshall, Jean S.; Rowter, Derek; Al-Afif, Ayham; Anderson, Robert

    2011-01-01

    Vascular perturbation is a hallmark of severe forms of dengue disease. We show here that antibody-enhanced dengue virus infection of primary human cord blood-derived mast cells (CBMCs) and the human mast cell-like line HMC-1 results in the release of factor(s) which activate human endothelial cells, as evidenced by increased expression of the adhesion molecules ICAM-1 and VCAM-1. Endothelial cell activation was prevented by pretreatment of mast cell-derived supernatants with a tumor necrosis factor (TNF)-specific blocking antibody, thus identifying TNF as the endothelial cell-activating factor. Our findings suggest that mast cells may represent an important source of TNF, promoting vascular endothelial perturbation following antibody-enhanced dengue virus infection. PMID:21068256

  11. Vitamin D-Regulated MicroRNAs: Are They Protective Factors against Dengue Virus Infection?

    PubMed Central

    Arboleda, John F.; Urcuqui-Inchima, Silvio

    2016-01-01

    Over the last few years, an increasing body of evidence has highlighted the critical participation of vitamin D in the regulation of proinflammatory responses and protection against many infectious pathogens, including viruses. The activity of vitamin D is associated with microRNAs, which are fine tuners of immune activation pathways and provide novel mechanisms to avoid the damage that arises from excessive inflammatory responses. Severe symptoms of an ongoing dengue virus infection and disease are strongly related to highly altered production of proinflammatory mediators, suggesting impairment in homeostatic mechanisms that control the host's immune response. Here, we discuss the possible implications of emerging studies anticipating the biological effects of vitamin D and microRNAs during the inflammatory response, and we attempt to extrapolate these findings to dengue virus infection and to their potential use for disease management strategies. PMID:27293435

  12. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model

    SciTech Connect

    Perna, J.J.; Mannix, M.L.; Rooney, J.F.; Notkins, A.L.; Straus, S.E.

    1987-09-01

    Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpes simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation.

  13. Worldwide occurrence of virus-infections in filamentous marine brown algae

    NASA Astrophysics Data System (ADS)

    Müller, D. G.; Stache, B.

    1992-03-01

    Virus infections were detected in Ectocarpus siliculosus and Ectocarpus fasciculatus on the coasts of Ireland, California, Peru, southern South America, Australia and New Zealand; in three Feldmannia species on the coasts of Ireland, continental Chile and Archipelago Juan Fernandez (Chile); and in Leptonematella from Antarctica. Natural populations on the Irish coast contained 3% infected plants in E. fasciculatus, and less than 1% in Feldmannia simplex. On the Californian coast, 15 to 25% of Ectocarpus isolates were infected. Virus symptoms were absent in E. siliculosus from Peru, but appeared after meiosis in laboratory cultures. The virus particles in E. fasciculatus are identical in size and capsid structure to those reported for E. siliculosus, while the virus in F. simplex is smaller and has a different envelope. Our findings suggest that virus infections are a common and worldwide phenomenon in filamentous brown algae.

  14. Antiviral drugs other than zidovudine and immunomodulating therapies in human immunodeficiency virus infection. An overview.

    PubMed

    Clumeck, N; Hermans, P

    1988-08-29

    Although the management of patients with human immunodeficiency virus infections has focused on the treatment of opportunistic infections, or acquired immune deficiency syndrome (AIDS)-related cancers in end stages of the disease, therapies now aim at preventing the natural progression of the underlying disease. In addition to zidovudine many investigational drugs are proposed to treat AIDS-related complex patients. Most of these therapies can be divided into two major groups: (1) The first group includes agents with antiretroviral properties: nucleoside analogues, such as 2'-3'-dideoxycytidine and ribavirin, suramin, antimoniotungstate (heteropolyanion-23), foscarnet (phosphonoformate), interferons, peptide T, castanospermine, dextran sulfate, AL721, or ampligen. (2) The second group aims to restore the defective immune system; it includes thymosin (thymopentin), interleukin-2, cyclosporine, plasmapheresis, bone marrow transplantation, inosine, sodium diethyldithiocarbamate, methionine-enkephalin and carrisyn. At present, no drug other than zidovudine has proved as monotherapy to lengthen survival of human immunodeficiency virus-infected patients. PMID:2457313

  15. Susceptibility to virus infection with exposure to nitrogen dioxide. Research report, January 1984-July 1987

    SciTech Connect

    Kulle, T.J.; Clements, M.L.

    1988-01-01

    The interaction between nitrogen dioxide (NO/sub 2/) exposure and human susceptibility to respiratory virus infection was investigated in a placebo-controlled, randomized, blinded trial conducted in an environmentally controlled research chamber. Healthy, nonsmoking volunteers, 18 to 35 years old, who were seronegative to influenza A/Korea/82 (H/sub 3/N/sub 2/) virus, breathed either filtered air or NO/sub 2/ for two hours a day for three consecutive days. Live, attenuated cold-adapted influenza A/Korea/82 reassortant virus was administered intranasally to all subjects after the second day of exposure. No adverse changes in pulmonary function or nonspecific airway reaction to methacholine were observed after NO/sub 2/ exposure, virus infection, or both. Although the differences were not statistically significant, the groups exposed to NO/sub 2/ in year 3 became infected more often (91%) than those exposed only to air (71%).

  16. CNS Recruitment of CD8+ T Lymphocytes Specific for a Peripheral Virus Infection Triggers Neuropathogenesis during Polymicrobial Challenge

    PubMed Central

    Matullo, Christine M.; O'Regan, Kevin J.; Curtis, Mark; Rall, Glenn F.

    2011-01-01

    Although viruses have been implicated in central nervous system (CNS) diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV) and peripherally restricted lymphocytic choriomeningitis virus (LCMV). While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35%) of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack. PMID:22216008

  17. Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

    PubMed Central

    Teng, Chung-Jen; Liu, Han-Tsung; Liu, Chun-Yu; Hsih, Chi-Hsiu; Pai, Jih-Tung; Gau, Jyh-Pyng; Liu, Jin-Hwang; Chiou, Tzeon-Jye; Hsu, Hui-Chi; Chen, Po-Min; Tzeng, Cheng-Hwai; Yu, Yuan-Bin

    2011-01-01

    OBJECTIVES: Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection. METHODS: From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV) and C viruses (HCV). Clinical parameters and outcome variables were retrieved via a medical chart review. RESULTS: The estimated prevalences of chronic HBV and HCV infections were 11.0% (n = 17) and 9.0% (n = 14), respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3% vs. 25.0%). The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0% vs. 12.0%, and hyperbilirubinemia, 20.0% vs. 1.6%, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months). The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/dL were independent factors associated with poor prognosis. CONCLUSION: Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory. PMID:22189730

  18. T-cell memory: lessons from Epstein-Barr virus infection in man.

    PubMed Central

    Rickinson, A B; Callan, M F; Annels, N E

    2000-01-01

    Epstein-Barr virus offers an ideal opportunity to follow the human T-cell response to a virus infection over time from its acute primary phase, as seen in infectious mononucleosis patients, into the memory phase that accompanies life-long virus persistence. Here we review recent evidence on the development and maturation of cytotoxic T-cell memory using this viral system. PMID:10794060

  19. Loss of transformed phenotype upon senescence of Rous sarcoma virus-infected chicken neuroretinal cells.

    PubMed Central

    Seigel, G M; Notter, M F

    1992-01-01

    Success in obtaining permanent Rous sarcoma virus-infected chicken cell lines has been limited because of a senescence phenomenon. We show that a diminished, transformed phenotype, followed by dramatic morphological changes, precedes senescence. These changes are associated with continued expression of pp60v-src, as well as specific alterations in expression of two possible phosphorylated substrates of pp60v-src. Images PMID:1326672

  20. EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS

    EPA Science Inventory

    EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS (P. Singhl, D.W. Winsett2, M.J. Daniels2,
    C.A.J. Dick', K.B. Adlerl and M.I. Gilmour2, INCSU, Raleigh, N.C., 2NHEERL/ORD/ USEPA, RTP, N.C. and 3UNC, Chapel Hill, N.C.)The interaction between ...

  1. Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype

    PubMed Central

    Campbell, Gillian M.; Nicol, Marlynne Q.; Dransfield, Ian; Shaw, Darren J.; Nash, Anthony A.

    2015-01-01

    The role of the macrophage in influenza virus infection is complex. Macrophages are critical for resolution of influenza virus infections but implicated in morbidity and mortality in severe infections. They can be infected with influenza virus and consequently macrophage infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus infection and therefore studied the infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and TNF-α, and TNF-α expression was further upregulated following infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following infection, expression of these markers was downregulated whilst expression of iNOS and TNF-α was upregulated. Thus, infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of pro-inflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection. PMID:26297234

  2. Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype.

    PubMed

    Campbell, Gillian M; Nicol, Marlynne Q; Dransfield, Ian; Shaw, Darren J; Nash, Anthony A; Dutia, Bernadette M

    2015-10-01

    The role of the macrophage in influenza virus infection is complex. Macrophages are critical for resolution of influenza virus infections but implicated in morbidity and mortality in severe infections. They can be infected with influenza virus and consequently macrophage infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus infection and therefore studied the infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and TNF-α, and TNF-α expression was further upregulated following infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following infection, expression of these markers was downregulated whilst expression of iNOS and TNF-α was upregulated. Thus, infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of pro-inflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection. PMID:26297234

  3. A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection

    PubMed Central

    Vereecke, Lars; Mc Guire, Conor; Sze, Mozes; Schuijs, Martijn J.; Willart, Monique; Itati Ibañez, Lorena; Hammad, Hamida; Lambrecht, Bart N.; Beyaert, Rudi; Saelens, Xavier; van Loo, Geert

    2016-01-01

    A20 negatively regulates multiple inflammatory signalling pathways. We here addressed the role of A20 in club cells (also known as Clara cells) of the bronchial epithelium in their response to influenza A virus infection. Club cells provide a niche for influenza virus replication, but little is known about the functions of these cells in antiviral immunity. Using airway epithelial cell-specific A20 knockout (A20AEC-KO) mice, we show that A20 in club cells critically controls innate immune responses upon TNF or double stranded RNA stimulation. Surprisingly, A20AEC-KO mice are better protected against influenza A virus challenge than their wild type littermates. This phenotype is not due to decreased viral replication. Instead host innate and adaptive immune responses and lung damage are reduced in A20AEC-KO mice. These attenuated responses correlate with a dampened cytotoxic T cell (CTL) response at later stages during infection, indicating that A20AEC-KO mice are better equipped to tolerate Influenza A virus infection. Expression of the chemokine CCL2 (also named MCP-1) is particularly suppressed in the lungs of A20AEC-KO mice during later stages of infection. When A20AEC-KO mice were treated with recombinant CCL2 the protective effect was abrogated demonstrating the crucial contribution of this chemokine to the protection of A20AEC-KO mice to Influenza A virus infection. Taken together, we propose a mechanism of action by which A20 expression in club cells controls inflammation and antiviral CTL responses in response to influenza virus infection. PMID:26815999

  4. Zika virus infection in a traveller returning to Europe from Brazil, March 2015.

    PubMed

    Zammarchi, L; Tappe, D; Fortuna, C; Remoli, M E; Günther, S; Venturi, G; Bartoloni, A; Schmidt-Chanasit, J

    2015-01-01

    We report a case of laboratory-confirmed Zika virus infection imported into Europe from the Americas. The patient developed fever, rash, and oedema of hands and feet after returning to Italy from Brazil in late March 2015. The case highlights that, together with chikungunya virus and dengue virus, three major arboviruses are now co-circulating in Brazil. These arboviruses represent a burden for the healthcare systems in Brazil and other countries where competent mosquito vectors are present. PMID:26084316

  5. [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

  6. Proliferation of Rous sarcoma virus-infected, but not of normal, chicken fibroblasts in oxygen-enriched environment: preliminary report.

    PubMed

    Mitchell, R S; Elgas, R J; Balk, S D

    1976-04-01

    Both normal and Rous sarcoma virus-infected chicken fibroblasts proliferate in an incubator containing 95% air, 5% CO2. In an incubator atmosphere enriched with oxygen, however, the normal fibroblasts are maintained without proliferation, while the Rous sarcoma virus-infected fibroblasts continue to proliferate. This suggests that a respiratory function may be involved in the regulation of proliferation of normal cells, and that neoplastic cells may proliferate autonomously because of a deficiency in this regulatory function. PMID:177983

  7. Peptide motif analysis predicts lymphocytic choriomeningitis virus as trigger for multiple sclerosis.

    PubMed

    Hogeboom, Charissa

    2015-10-01

    The etiology of multiple sclerosis (MS) involves both genetic and environmental factors. Genetically, the strongest link is with HLA DRB1*1501, but the environmental trigger, probably a virus, remains uncertain. This investigation scans a panel of proteins from encephalitogenic viruses for peptides homologous to the primary autoantigen from myelin basic protein (MBP), then evaluates candidate peptides against a motif required for T cell cross-reactivity and compares viral prevalence patterns to epidemiological characteristics of MS. The only peptide meeting criteria for cross-reactivity with MBP was one from lymphocytic choriomeningitis virus (LCMV), a zoonotic agent. In contrast to current candidates such as Epstein-Barr virus, the distribution of LCMV is consistent with epidemiological features of MS, including concentration in the temperate zone, higher prevalence farther from the equator, and increased prevalence in proximity to regions of peak MS incidence, while lack of person-to-person transmission is consistent with low MS concordance across monozygotic twins. Further, LCMV blocks induction of type I interferon (IFN). Hypothetically this would dysregulate immune processes in favor of proinflammatory pathways as well as upregulating HLA class II and providing more binding sites for autoantigen. The combination of molecular mimicry with virally-induced immune dysregulation has the potential to explain aspects of autoimmunity not addressed by either mechanism alone. PMID:26319106

  8. Lymphocytic choriomeningitis virus uses a novel endocytic pathway for infectious entry via late endosomes

    SciTech Connect

    Quirin, Katharina; Eschli, Bruno; Scheu, Isabella; Poort, Linda; Kartenbeck, Juergen; Helenius, Ari

    2008-08-15

    The endocytic entry of lymphocytic choriomeningitis virus (LCMV) into host cells was compared to the entry of viruses known to exploit clathrin or caveolae/raft-dependent pathways. Pharmacological inhibitors, expression of pathway-specific dominant-negative constructs, and siRNA silencing of clathrin together with electron and light microscopy provided evidence that although a minority population followed a classical clathrin-mediated mechanism of entry, the majority of these enveloped RNA viruses used a novel endocytic route to late endosomes. The pathway was clathrin, dynamin-2, actin, Arf6, flotillin-1, caveolae, and lipid raft independent but required membrane cholesterol. Unaffected by perturbation of Rab5 or Rab7 and apparently without passing through Rab5/EEA1-positive early endosomes, the viruses reached late endosomes and underwent acid-induced penetration. This membrane trafficking route between the plasma membrane and late endosomes may function in the turnover of a select group of surface glycoproteins such as the dystroglycan complex, which serves as the receptor of LCMV.

  9. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever.

    PubMed

    Zapata, Juan C; Pauza, C David; Djavani, Mahmoud M; Rodas, Juan D; Moshkoff, Dmitry; Bryant, Joseph; Ateh, Eugene; Garcia, Cybele; Lukashevich, Igor S; Salvato, Maria S

    2011-11-01

    Arenaviruses such as Lassa fever virus (LASV) and lymphocytic choriomeningitis virus (LCMV) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (VHF) in non-human primates and in human beings. LCMV is considerably more benign for human beings than Lassa virus, however certain strains, like the LCMV-WE strain, can cause severe disease when the virus is delivered as a high-dose inoculum. Here we describe a rhesus macaque model for Lassa fever that employs a virulent strain of LCMV. Since LASV must be studied within Biosafety Level-4 (BSL-4) facilities, the LCMV-infected macaque model has the advantage that it can be used at BSL-3. LCMV-induced disease is rarely as severe as other VHF, but it is similar in cases where vascular leakage leads to lethal systemic failure. The LCMV-infected macaque has been valuable for describing the course of disease with differing viral strains, doses and routes of infection. By monitoring system-wide changes in physiology and gene expression in a controlled experimental setting, it is possible to identify events that are pathognomonic for developing VHF and potential treatment targets. PMID:21820469

  10. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever

    PubMed Central

    Zapata, Juan C.; Pauza, C. David; Djavani, Mahmoud M.; Rodas, Juan D.; Moshkoff, Dmitry; Bryant, Joseph; Ateh, Eugene; Garcia, Cybele; Lukashevich, Igor S.; Salvato, Maria S.

    2011-01-01

    Arenaviruses such as Lassa fever virus (LASV) and lymphocytic choriomeningitis virus (LCMV) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (VHF) in non-human primates and in human beings. LCMV is considerably more benign for human beings than Lassa virus, however certain strains, like the LCMV-WE strain, can cause severe disease when the virus is delivered as a high-dose inoculum. Here we describe a rhesus macaque model for Lassa fever that employs a virulent strain of LCMV. Since LASV must be studied within Biosafety Level-4 (BSL-4) facilities, the LCMV-infected macaque model has the advantage that it can be used at BSL-3. LCMV-induced disease is rarely as severe as other VHF, but it is similar in cases where vascular leakage leads to lethal systemic failure. The LCMV-infected macaque has been valuable for describing the course of disease with differing viral strains, doses and routes of infection. By monitoring system-wide changes in physiology and gene expression in a controlled experimental setting, it is possible to identify events that are pathognomonic for developing VHF and potential treatment targets. PMID:21820469

  11. Impaired learning resulting from respiratory syncytial virus infection.

    PubMed

    Espinoza, Janyra A; Bohmwald, Karen; Céspedes, Pablo F; Gómez, Roberto S; Riquelme, Sebastián A; Cortés, Claudia M; Valenzuela, Javier A; Sandoval, Rodrigo A; Pancetti, Floria C; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2013-05-28

    Respiratory syncytial virus (RSV) is the major cause of respiratory illness in infants worldwide. Neurologic alterations, such as seizures and ataxia, have been associated with RSV infection. We demonstrate the presence of RSV proteins and RNA in zones of the brain--such as the hippocampus, ventromedial hypothalamic nucleus, and brainstem--of infected mice. One month after disease resolution, rodents showed behavioral and cognitive impairment in marble burying (MB) and Morris water maze (MWM) tests. Our data indicate that the learning impairment caused by RSV is a result of a deficient induction of long-term potentiation in the hippocampus of infected animals. In addition, immunization with recombinant bacillus Calmette-Guérin (BCG) expressing RSV nucleoprotein prevented behavioral disorders, corroborating the specific effect of RSV infection over the central nervous system. Our findings provide evidence that RSV can spread from the airways to the central nervous system and cause functional alterations to the brain, both of which can be prevented by proper immunization against RSV. PMID:23650398

  12. Bovine Lactoferrin Inhibits Toscana Virus Infection by Binding to Heparan Sulphate

    PubMed Central

    Pietrantoni, Agostina; Fortuna, Claudia; Remoli, Maria Elena; Ciufolini, Maria Grazia; Superti, Fabiana

    2015-01-01

    Toscana virus is an emerging sandfly-borne bunyavirus in Mediterranean Europe responsible for neurological diseases in humans. It accounts for about 80% of paediatric meningitis cases during the summer. Despite the important impact of Toscana virus infection-associated disease on human health, currently approved vaccines or effective antiviral treatments are not available. In this research, we have analyzed the effect of bovine lactoferrin, a bi-globular iron-binding glycoprotein with potent antimicrobial and immunomodulatory activities, on Toscana virus infection in vitro. Our results showed that lactoferrin was capable of inhibiting Toscana virus replication in a dose-dependent manner. Results obtained when lactoferrin was added to the cells during different phases of viral infection showed that lactoferrin was able to prevent viral replication when added during the viral adsorption step or during the entire cycle of virus infection, demonstrating that its action takes place in an early phase of viral infection. In particular, our results demonstrated that the anti-Toscana virus action of lactoferrin took place on virus attachment to the cell membrane, mainly through a competition for common glycosaminoglycan receptors. These findings provide further insights on the antiviral activity of bovine lactoferrin. PMID:25643293

  13. Dietary lactosucrose suppresses influenza A (H1N1) virus infection in mice

    PubMed Central

    KISHINO, Eriko; TAKEMURA, Naho; MASAKI, Hisaharu; ITO, Tetsuya; NAKAZAWA, Masatoshi

    2015-01-01

    This study examined the effects of lactosucrose (4G-β-D-galactosylsucrose) on influenza A virus infections in mice. First, the effects of lactosucrose on fermentation in the cecum and on immune function were investigated. In female BALB/c mice, lactosucrose supplementation for 6 weeks promoted cecal fermentation and increased both secretory IgA (SIgA) levels in feces and total IgA and IgG2a concentrations in serum. Both the percentage of CD4+ T cells in Peyer’s patches and the cytotoxic activity of splenic natural killer (NK) cells increased significantly in response to lactosucrose. Next, we examined the effects of lactosucrose on low-dose influenza A virus infection in mice. After 2 weeks of dietary supplementation with lactosucrose, the mice were infected with low-dose influenza A virus. At 7 days post infection, a comparison with control mice showed that weight loss was suppressed, as were viral titers in the lungs. In the spleens of lactosucrose-fed mice, there was an increase in the percentage of NK cells. Lastly, mice fed lactosucrose were challenged with a lethal dose of influenza A virus. The survival rate of these mice was significantly higher than that of mice fed a control diet. These results suggested that lactosucrose supplementation suppresses influenza A virus infection by augmenting innate immune responses and enhancing cellular and mucosal immunity. PMID:26594606

  14. High rate of unrecognized dengue virus infection in parts of the rainforest region of Nigeria.

    PubMed

    Onoja, A B; Adeniji, J A; Olaleye, O D

    2016-08-01

    Outbreaks and sporadic dengue virus infections continue to occur in Africa. Several reports of dengue among travellers returning from some African countries to Europe and North America have raised concerns about the epidemiological situation in Africa. We investigated recent dengue infections in febrile patients during the rainy season in various urban centres in the rainforest region of Nigeria, West Africa. This cross-sectional study was conducted for 8 months in 2014 with study participants from Adeoyo Hospital Yemetu - Ibadan, Nigeria. Plasma were collected from 274 febrile patients residing in 11 Local Government Areas of Oyo State. IgM antibodies were determined using semi-quantitative sandwich ELISA. Data was analyzed using Chi - Square and Fisher's exact test with SPSS 16.0. An overall prevalence of 23.4% dengue virus infection was found among study participants. Highest monthly prevalence of 40% was in April and August. The monthly distribution pattern of dengue virus infection indicates efficient virus transmission. Routine diagnosis will enhance dengue virus surveillance and improve patient care in West Africa. PMID:27140859

  15. Effect of Host Cell on Distribution of a Lysosomal Enzyme During Virus Infection

    PubMed Central

    Sato, Kosaburo; Righthand, Fay; Karzon, David T.

    1971-01-01

    The time of appearance of a lysosomal enzyme, β-glucuronidase, in the medium of cells infected with either measles virus or echovirus 6 varied with the host cell system. Replication and release of virus preceded leakage of β-glucuronidase from green monkey kidney cells. In contrast, extracellular enzyme appeared before replication and release of virus in human amnion cells. Hydrocortisone depressed enzyme leakage but did not retard replication of measles virus or viral-induced cytopathology. The intracellular distribution of β-glucuronidase in uninfected and measles virus-infected cells was also studied. Measles virus infection altered the position of particulate-bound β-glucuronidase in linear sucrose gradients prior to substantial release of this enzyme intra- and extracellularly. At early stages in infection, most of the cell-associated virus banded with particulate-bound enzyme in the middle of the gradient. As infection progressed, separation of measles virus infectivity from enzyme activity occurred, and intracellular virus was recovered near the meniscus of sucrose gradients. PMID:5000115

  16. Mechanisms of immunity in post-exposure vaccination against Ebola virus infection.

    PubMed

    Bradfute, Steven B; Anthony, Scott M; Stuthman, Kelly S; Ayithan, Natarajan; Tailor, Prafullakumar; Shaia, Carl I; Bray, Mike; Ozato, Keiko; Bavari, Sina

    2015-01-01

    Ebolaviruses can cause severe hemorrhagic fever that is characterized by rapid viral replication, coagulopathy, inflammation, and high lethality rates. Although there is no clinically proven vaccine or treatment for Ebola virus infection, a virus-like particle (VLP) vaccine is effective in mice, guinea pigs, and non-human primates when given pre-infection. In this work, we report that VLPs protect Ebola virus-infected mice when given 24 hours post-infection. Analysis of cytokine expression in serum revealed a decrease in pro-inflammatory cytokine and chemokine levels in mice given VLPs post-exposure compared to infected, untreated mice. Using knockout mice, we show that VLP-mediated post-exposure protection requires perforin, B cells, macrophages, conventional dendritic cells (cDCs), and either CD4+ or CD8+ T cells. Protection was Ebola virus-specific, as marburgvirus VLPs did not protect Ebola virus-infected mice. Increased antibody production in VLP-treated mice correlated with protection, and macrophages were required for this increased production. However, NK cells, IFN-gamma, and TNF-alpha were not required for post-exposure-mediated protection. These data suggest that a non-replicating Ebola virus vaccine can provide post-exposure protection and that the mechanisms of immune protection in this setting require both increased antibody production and generation of cytotoxic T cells. PMID:25785602

  17. Viewpoint: factors involved in type I interferon responses during porcine virus infections.

    PubMed

    Summerfield, Artur

    2012-07-15

    Since type I interferon (IFN-I) is considered a potent antiviral defence mechanism, it is not surprising that during evolution viruses have development of various mechanisms to counteract IFN-I induction or release. Despite this, certain virus infections are associated with very high levels of systemic IFN-I. One explanation for this observation is the presence of plasmacytoid dendritic cells (pDC), which are able to produce high levels of IFN-I despite the presence of viral IFN-I antagonists. Examples of virus infection in pigs including classical swine fever virus, influenza virus, foot-and-mouth disease virus, and porcine circo virus type 2 highlight factors involved in controlling such responses and illustrate potential negative and positive effects for the host. Based on published data, we propose that in addition to the ability to activate pDC, the ability to spread systemically, and the tropism for lymphoid tissue also represent important factors contributing to strong systemic IFN-I responses during certain virus infections. PMID:21458079

  18. Mechanisms of Immunity in Post-Exposure Vaccination against Ebola Virus Infection

    PubMed Central

    Bradfute, Steven B.; Anthony, Scott M.; Stuthman, Kelly S.; Ayithan, Natarajan; Tailor, Prafullakumar; Shaia, Carl I.; Bray, Mike; Ozato, Keiko; Bavari, Sina

    2015-01-01

    Ebolaviruses can cause severe hemorrhagic fever that is characterized by rapid viral replication, coagulopathy, inflammation, and high lethality rates. Although there is no clinically proven vaccine or treatment for Ebola virus infection, a virus-like particle (VLP) vaccine is effective in mice, guinea pigs, and non-human primates when given pre-infection. In this work, we report that VLPs protect Ebola virus-infected mice when given 24 hours post-infection. Analysis of cytokine expression in serum revealed a decrease in pro-inflammatory cytokine and chemokine levels in mice given VLPs post-exposure compared to infected, untreated mice. Using knockout mice, we show that VLP-mediated post-exposure protection requires perforin, B cells, macrophages, conventional dendritic cells (cDCs), and either CD4+ or CD8+ T cells. Protection was Ebola virus-specific, as marburgvirus VLPs did not protect Ebola virus-infected mice. Increased antibody production in VLP-treated mice correlated with protection, and macrophages were required for this increased production. However, NK cells, IFN-gamma, and TNF-alpha were not required for post-exposure-mediated protection. These data suggest that a non-replicating Ebola virus vaccine can provide post-exposure protection and that the mechanisms of immune protection in this setting require both increased antibody production and generation of cytotoxic T cells. PMID:25785602

  19. Bovine lactoferrin inhibits Toscana virus infection by binding to heparan sulphate.

    PubMed

    Pietrantoni, Agostina; Fortuna, Claudia; Remoli, Maria Elena; Ciufolini, Maria Grazia; Superti, Fabiana

    2015-02-01

    Toscana virus is an emerging sandfly-borne bunyavirus in Mediterranean Europe responsible for neurological diseases in humans. It accounts for about 80% of paediatric meningitis cases during the summer. Despite the important impact of Toscana virus infection-associated disease on human health, currently approved vaccines or effective antiviral treatments are not available. In this research, we have analyzed the effect of bovine lactoferrin, a bi-globular iron-binding glycoprotein with potent antimicrobial and immunomodulatory activities, on Toscana virus infection in vitro. Our results showed that lactoferrin was capable of inhibiting Toscana virus replication in a dose-dependent manner. Results obtained when lactoferrin was added to the cells during different phases of viral infection showed that lactoferrin was able to prevent viral replication when added during the viral adsorption step or during the entire cycle of virus infection, demonstrating that its action takes place in an early phase of viral infection. In particular, our results demonstrated that the anti-Toscana virus action of lactoferrin took place on virus attachment to the cell membrane, mainly through a competition for common glycosaminoglycan receptors. These findings provide further insights on the antiviral activity of bovine lactoferrin. PMID:25643293

  20. Airway Epithelial Orchestration of Innate Immune Function in Response to Virus Infection. A Focus on Asthma.

    PubMed

    Ritchie, Andrew I; Jackson, David J; Edwards, Michael R; Johnston, Sebastian L

    2016-03-01

    Asthma is a very common respiratory condition with a worldwide prevalence predicted to increase. There are significant differences in airway epithelial responses in asthma that are of particular interest during exacerbations. Preventing exacerbations is a primary aim when treating asthma because they often necessitate unscheduled healthcare visits and hospitalizations and are a significant cause of morbidity and mortality. The most common cause of asthma exacerbations is a respiratory virus infection, of which the most likely type is rhinovirus infection. This article focuses on the role played by the epithelium in orchestrating the innate immune responses to respiratory virus infection. Recent studies show impaired bronchial epithelial cell innate antiviral immune responses, as well as augmentation of a pro-Th2 response characterized by the epithelial-derived cytokines IL-25 and IL-33, crucial in maintaining the Th2 cytokine response to virus infection in asthma. A better understanding of the mechanisms of these abnormal immune responses has the potential to lead to the development of novel therapeutic targets for virus-induced exacerbations. The aim of this article is to highlight current knowledge regarding the role of viruses and immune modulation in the asthmatic epithelium and to discuss exciting areas for future research and novel treatments. PMID:27027954

  1. Immunofluorescence studies of disseminated Hantaan virus infection of suckling mice.

    PubMed Central

    Kurata, T; Tsai, T F; Bauer, S P; McCormick, J B

    1983-01-01

    Hantaan virus, the etiological agent of Korean hemorrhagic fever, was inoculated intracerebrally or intraperitoneally into suckling mice, and the course of the infection was followed by infectivity titration and immunofluorescence studies. Mice became ill and were moribund by 13 to 14 days postinfection. In mice inoculated either intracerebrally or intraperitoneally, virus antigen was present in brain, heart, lungs, liver, and kidney. Less consistently, specific fluorescence was observed in spleen, pituitary gland, thymus, lymph nodes, adrenal, pancreas, salivary glands, trigeminal ganglia, adipose tissue, intestine, and muscle. In all of these tissues, the primary target of infection was the capillary endothelium. In mice inoculated intracerebrally, virus antigen was present mainly in choroid plexus, hippocampal nuclei, and meninges, but in mice inoculated intraperitoneally, central nervous system infection was marked by antigen accumulation in cortical nuclei and thalamus. Images PMID:6134678

  2. Pathogenesis of Hendra and Nipah virus infection in humans.

    PubMed

    Escaffre, Olivier; Borisevich, Viktoriya; Rockx, Barry

    2013-04-01

    Hendra virus (HeV) and Nipah virus (NiV) are emerging zoonotic viruses that cause severe and often lethal respiratory illness and encephalitis in humans. Henipaviruses can infect a wide range of species and human-to-human transmission has been observed for NiV. While the exact route of transmission in humans is not known, experimental infection in different animal species suggests that infection can be efficiently initiated after respiratory challenge. The limited data on histopathological changes in fatal human cases of HeV and NiV suggest that endothelial cells are an important target during the terminal stage of infection; however, it is unknown where these viruses initially establish infection and how the virus disseminates from the respiratory tract to the central nervous system and other organs. Here we review the current concepts in henipavirus pathogenesis in humans. PMID:23592639

  3. Epidermal multinucleated giant cells are not always a histopathologic clue to a herpes virus infection: multinucleated epithelial giant cells in the epidermis of lesional skin biopsies from patients with acantholytic dermatoses can histologically mimic a herpes virus infection

    PubMed Central

    Cohen, Philip R.; Paravar, Taraneh; Lee, Robert A.

    2014-01-01

    Background: Multinucleated giant cells in the epidermis can either be epithelial or histiocytic. Epithelial multinucleated giant cells are most often associated with herpes virus infections. Purpose: To review the histologic differential diagnosis of conditions with epithelial and histiocytic multinucleated giant cells—since multinucleated giant cells in the epidermis are not always pathognomonic of a cutaneous herpes virus infection—and to summarize dermatoses in which herpes virus infection has been observed to coexist. Methods: Two individuals with acantholytic dermatoses whose initial lesional skin biopsies showed multinucleated epithelial giant cells suggestive of a herpes virus infection are reported. Using the PubMed database, an extensive literature search was performed on multinucleated giant cell (and epidermis, epithelial, and histiocytic) and herpes virus infection. Relevant papers were reviewed to discover the skin conditions with either multinucleated giant cells in the epidermis or coincident cutaneous herpes virus infection. Results: Initial skin biopsies from patients with either pemphigus vulgaris or transient acantholytic dermatosis mimicked herpes virus infection; however, laboratory studies and repeat biopsies established the correct diagnosis of their acantholytic dermatosis. Hence, epidermal multinucleated giant cells are not always a histopathologic clue to a herpes virus infection. Indeed, epithelial multinucleated giant cells in the epidermis can be observed not only in the presence of infection (herpes virus), but also acantholytic dermatoses and tumors (trichoepithelioma and pleomorphic basal cell carcinoma). Histiocytic multinucleated giant cells in the epidermis can be observed in patients with either giant cell lichenoid dermatitis or lichen nitidus of the palms. Conclusions: Epithelial and histiocytic multinucleated giant cell can occur in the epidermis. Keratinocyte-derived multinucleated giant cells are most commonly associated

  4. Evaluation of monkeypox virus infection of black-tailed prairie dogs (Cynomys ludovicianus) using in vivo bioluminescent imaging.

    PubMed

    Falendysz, Elizabeth A; Londoño-Navas, Angela M; Meteyer, Carol U; Pussini, Nicola; Lopera, Juan G; Osorio, Jorge E; Rocke, Tonie E

    2014-07-01

    Monkeypox (MPX) is a re-emerging zoonotic disease that is endemic in Central and West Africa, where it can cause a smallpox-like disease in humans. Despite many epidemiologic and field investigations of MPX, no definitive reservoir species has been identified. Using recombinant viruses expressing the firefly luciferase (luc) gene, we previously demonstrated the suitability of in vivo bioluminescent imaging (BLI) to study the pathogenesis of MPX in animal models. Here, we evaluated BLI as a novel approach for tracking MPX virus infection in black-tailed prairie dogs (Cynomys ludovicianus). Prairie dogs were affected during a multistate outbreak of MPX in the US in 2003 and have since been used as an animal model of this disease. Our BLI results were compared with PCR and virus isolation from tissues collected postmortem. Virus was easily detected and quantified in skin and superficial tissues by BLI before and during clinical phases, as well as in subclinical secondary cases, but was not reliably detected in deep tissues such as the lung. Although there are limitations to viral detection in larger wild rodent species, BLI can enhance the use of prairie dogs as an animal model of MPX and can be used for the study of infection, disease progression, and transmission in potential wild rodent reservoirs. PMID:24779460

  5. [Acute encephalitis. Neuropsychiatric manifestations as expression of influenza virus infection].

    PubMed

    Moreno-Flagge, Noris; Bayard, Vicente; Quirós, Evelia; Alonso, Tomás

    2009-01-01

    The aim is to review the encephalitis in infants and adolescents as well as its etiology, clinical manifestation, epidemiology, physiopathology, diagnostic methods and treatment, and the neuropsyquiatric signs appearing an influenza epidemy. Encephalitis is an inflammation of the central nervous system (CNS) which involves the brain. The clinical manifestations usually are: headache, fever and confusional stage. It could also be manifested as seizures, personality changes, or psiqyiatric symptoms. The clinical manifestations are related to the virus and the cell type affected in the brain. A meningitis or encephalopathy need to be ruled out. It could be present as an epidemic or isolated form, beeing this the most frequent form. It could be produced by a great variety of infections agents including virus, bacterias, fungal and parasitic. Viral causes are herpesvirus, arbovirus, rabies and enterovirus. Bacterias such as Borrelia burgdorferi, Rickettsia and Mycoplasma neumoniae. Some fungal causes are: Coccidioides immitis and Histoplasma capsulatum. More than 100 agents are related to encephalitis. The diagnosis of encephalitis is a challenge for the clinician and its infectious etiology is clear in only 40 to 70% of all cases. The diagnosis of encephalitis can be established with absolute certainty only by the microscopic examination of brain tissue. Epidemiology is related to age of the patients, geographic area, season, weather or the host immune system. Early intervention can reduce the mortality rate and sequels. We describe four patients with encephalitis and neuropsychiatric symptoms during an influenza epidemic. PMID:19240010

  6. Noninvasive Monitoring of Hepatic Damage from Hepatitis C Virus Infection

    PubMed Central

    Alavez-Ramírez, J.; Fuentes-Allen, J. L.; López-Estrada, J.

    2011-01-01

    The mathematical model for the dynamics of the hepatitis C proposed in Avendaño et al. (2002), with four populations (healthy and unhealthy hepatocytes, the viral load of the hepatitis C virus, and T killer cells), is revised. Showing that the reduced model obtained by considering only the first three of these populations, known as basic model, has two possible equilibrium states: the uninfected one where viruses are not present in the individual, and the endemic one where viruses and infected cells are present. A threshold parameter (the basic reproductive virus number) is introduced, and in terms of it, the global stability of both two possible equilibrium states is established. Other central result consists in showing, by model numerical simulations, the feasibility of monitoring liver damage caused by HCV, avoiding unnecessary biopsies and the undesirable related inconveniences/imponderables to the patient; another result gives a mathematical modelling basis to recently developed techniques for the disease assessment based essentially on viral load measurements. PMID:21331263

  7. Venezuelan Equine Encephalitis Virus Infection of Spiny Rats

    PubMed Central

    Carrara, Anne-Sophie; Gonzales, Marta; Ferro, Cristina; Tamayo, Margarita; Aronson, Judith; Paessler, Slobodan; Anishchenko, Michael; Boshell, Jorge

    2005-01-01

    Enzootic strains of Venezuelan equine encephalitis virus (VEEV) circulate in forested habitats of Mexico, Central, and South America, and spiny rats (Proechimys spp.) are believed to be the principal reservoir hosts in several foci. To better understand the host-pathogen interactions and resistance to disease characteristic of many reservoir hosts, we performed experimental infections of F1 progeny from Proechimys chrysaeolus collected at a Colombian enzootic VEEV focus using sympatric and allopatric virus strains. All animals became viremic with a mean peak titer of 3.3 log10 PFU/mL, and all seroconverted with antibody titers from 1:20 to 1:640, which persisted up to 15 months. No signs of disease were observed, including after intracerebral injections. The lack of detectable disease and limited histopathologic lesions in these animals contrast dramatically with the severe disease and histopathologic findings observed in other laboratory rodents and humans, and support their role as reservoir hosts with a long-term coevolutionary relationship to VEEV. PMID:15890116

  8. Extrahepatic manifestations of chronic hepatitis C virus infection.

    PubMed

    Cacoub, Patrice; Comarmond, Cloe; Domont, Fanny; Savey, Léa; Desbois, Anne C; Saadoun, David

    2016-02-01

    During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined. PMID:26862398

  9. Natural Bagaza virus infection in game birds in southern Spain

    PubMed Central

    2012-01-01

    In late summer 2010 a mosquito born flavivirus not previously reported in Europe called Bagaza virus (BAGV) caused high mortality in red-legged partridges (Alectoris rufa) and ring-necked pheasants (Phasianus colchicus). We studied clinical findings, lesions and viral antigen distribution in naturally BAGV infected game birds in order to understand the apparently higher impact on red-legged partridges. The disease induced neurologic signs in the two galliform species and, to a lesser extent, in common wood pigeons (Columba palumbus). In red-legged partridges infection by BAGV caused severe haemosiderosis in the liver and spleen that was absent in pheasants and less evident in common wood pigeons. Also, BAGV antigen was present in vascular endothelium in multiple organs in red-legged partridges, and in the spleen in common wood pigeons, while in ring-necked pheasants it was only detected in neurons and glial cells in the brain. These findings indicate tropism of BAGV for endothelial cells and a severe haemolytic process in red-legged partridges in addition to the central nervous lesions that were found in all three species. PMID:22966904

  10. Extrahepatic manifestations of chronic hepatitis C virus infection

    PubMed Central

    Comarmond, Cloe; Domont, Fanny; Savey, Léa; Desbois, Anne C.; Saadoun, David

    2016-01-01

    During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined. PMID:26862398

  11. [Border disease: a persistent virus infection in sheep (author's transl)].

    PubMed

    Terpstra, C

    1980-08-15

    Border disease (BD) is a congenital infection of sheep characterised by still-birth, abortion and the birth of weak lambs with nervous symptoms and sometimes an abnormally hairy birthcoat. The lambs are almost constantly trembling or shaking, they often have an erratic gait and in severe cases are unable to rise. The nervous signs are due to a defective myelinogensis of the central nervous system and tend to disappear at a later age. Many affected lambs die shortly after birth and those which survive usually show retarded growth. The disease is caused by a virus which is closely related to the virus of bovine virus diarrhoea (BVD). The virus may be isolated from every organ and is excreted with saliva, nasal discharge, urine and faeces. Clinically the diagnosis can be made with high probability when nervous signs and hairy birthcoat are both present. Laboratory diagnosis is based on the detection of antigen by immunofluorescence or virus isolation. In addition ewes of BD-affected lambs usually possess antibodies against BVD-virus. In some lambs, an immune response starts during prenatal life, others show a transient or lasting low level response at a later age, whereas still others remained serologically negative for at least 2 1/2 years. Asymptomatic virus carriers occur among lambs as well as among adult sheep. The persistently infected animals are continously shedding virus and thus maintain the infection in the flock. PMID:6252652

  12. Theiler's Virus Infection: Pathophysiology of Demyelination and Neurodegeneration

    PubMed Central

    Sato, Fumitaka; Tanaka, Hiroki; Hasanovic, Faris; Tsunoda, Ikuo

    2010-01-01

    Multiple sclerosis (MS) has been suggested to be an autoimmune demyelinating disease of the central nervous system (CNS), whose primary target is either myelin itself, or myelin-forming cells, the oligodendrocytes. Although axonal damage occurs in MS, it is regarded as a secondary event to the myelin damage. Here, the lesion develops from the myelin (outside) to the axons (inside) “Outside-In model”. The Outside-In model has been supported by an autoimmune model for MS, experimental autoimmune (allergic) encephalomyelitis (EAE). However, recently, 1) EAE-like disease has also been shown to be induced by immune responses against axons, and 2) immune responses against axons and neurons as well as neurodegeneration independent of inflammatory demyelination have been reported in MS, which can not be explained by the Outside-In model. Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) is a viral model for MS. In TMEV infection, axonal injury precedes demyelination, where the lesion develops from the axons (inside) to the myelin (outside) “Inside-Out model”. The initial axonal damage could result in the release of neuroantigens, inducing autoimmune responses against myelin antigens, which potentially attack the myelin from outside the nerve fiber. Thus, the Inside-Out and Outside-In models can make a “vicious” immunological cycle or initiate an immune cascade. PMID:20537875

  13. Natural Bagaza virus infection in game birds in southern Spain.

    PubMed

    Gamino, Virginia; Gutiérrez-Guzmán, Ana-Valeria; Fernández-de-Mera, Isabel G; Ortíz, José-Antonio; Durán-Martín, Mauricio; de la Fuente, José; Gortázar, Christian; Höfle, Ursula

    2012-01-01

    In late summer 2010 a mosquito born flavivirus not previously reported in Europe called Bagaza virus (BAGV) caused high mortality in red-legged partridges (Alectoris rufa) and ring-necked pheasants (Phasianus colchicus). We studied clinical findings, lesions and viral antigen distribution in naturally BAGV infected game birds in order to understand the apparently higher impact on red-legged partridges. The disease induced neurologic signs in the two galliform species and, to a lesser extent, in common wood pigeons (Columba palumbus). In red-legged partridges infection by BAGV caused severe haemosiderosis in the liver and spleen that was absent in pheasants and less evident in common wood pigeons. Also, BAGV antigen was present in vascular endothelium in multiple organs in red-legged partridges, and in the spleen in common wood pigeons, while in ring-necked pheasants it was only detected in neurons and glial cells in the brain. These findings indicate tropism of BAGV for endothelial cells and a severe haemolytic process in red-legged partridges in addition to the central nervous lesions that were found in all three species. PMID:22966904

  14. Theiler's Virus Infection: a Model for Multiple Sclerosis

    PubMed Central

    Oleszak, Emilia L.; Chang, J. Robert; Friedman, Herman; Katsetos, Christos D.; Platsoucas, Chris D.

    2004-01-01

    Both genetic background and environmental factors, very probably viruses, appear to play a role in the etiology of multiple sclerosis (MS). Lessons from viral experimental models suggest that many different viruses may trigger inflammatory demyelinating diseases resembling MS. Theiler's virus, a picornavirus, induces in susceptible strains of mice early acute disease resembling encephalomyelitis followed by late chronic demyelinating disease, which is one of the best, if not the best, animal model for MS. During early acute disease the virus replicates in gray matter of the central nervous system but is eliminated to very low titers 2 weeks postinfection. Late chronic demyelinating disease becomes clinically apparent approximately 2 weeks later and is characterized by extensive demyelinating lesions and mononuclear cell infiltrates, progressive spinal cord atrophy, and axonal loss. Myelin damage is immunologically mediated, but it is not clear whether it is due to molecular mimicry or epitope spreading. Cytokines, nitric oxide/reactive nitrogen species, and costimulatory molecules are involved in the pathogenesis of both diseases. Close similarities between Theiler's virus-induced demyelinating disease in mice and MS in humans, include the following: major histocompatibility complex-dependent susceptibility; substantial similarities in neuropathology, including axonal damage and remyelination; and paucity of T-cell apoptosis in demyelinating disease. Both diseases are immunologically mediated. These common features emphasize the close similarities of Theiler's virus-induced demyelinating disease in mice and MS in humans. PMID:14726460

  15. Acute disseminated encephalomyelitis associated with hepatitis A virus infection.

    PubMed

    Alehan, Füsun K; Kahveci, Suat; Uslu, Yasemin; Yildirim, Tülin; Yilmaz, Başak

    2004-06-01

    We describe the case of a 30-month-old boy who developed acute disseminated encephalomyelitis (ADEM) after hepatitis A virus (HAV) infection and ultimately died. As far as we know, this is only the second case of HAV-associated ADEM to be reported in the literature. The child was brought to hospital with fever, lethargy and weakness of 2 days duration. He had developed jaundice, abdominal pain and malaise 2 weeks beforehand and these problems had resolved within 2 days. Neurological examination revealed lethargy, generalised weakness and positive Babinski's signs bilaterally. Cerebrospinal fluid examination showed mild lymphocytic pleocytosis, increased protein and elevated anti-HAV IgM and IgG titres. Serum HAV IgM and IgG titres were also elevated. Despite aggressive treatment with ceftriaxone, acyclovir and anti-oedema measures, he developed papilloedema and coma within 24 hours of admission. Magnetic resonance imaging of the brain revealed diffuse cerebral oedema and multifocal hyperintensities on T2-weighted images, with most lesions in the white matter of both cerebral hemispheres. The diagnosis of ADEM was established and high-dose steroids and intravenous immunoglobulin were added to the treatment regimen. However, his clinical condition continued to deteriorate and he died on the 20th day in hospital. This case shows that HAV infection can be linked with ADEM. Patients with HAV infection should be examined carefully for central nervous system symptoms during follow-up. Likewise, the possibility of HAV infection should be investigated in cases of ADEM. PMID:15186542

  16. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas

    PubMed Central

    Barbian, Hannah J.; Decker, Julie M.; Bibollet-Ruche, Frederic; Galimidi, Rachel P.; West, Anthony P.; Learn, Gerald H.; Parrish, Nicholas F.; Iyer, Shilpa S.; Li, Yingying; Pace, Craig S.; Song, Ruijiang; Huang, Yaoxing; Denny, Thomas N.; Mouquet, Hugo; Martin, Loic; Acharya, Priyamvada; Zhang, Baoshan; Kwong, Peter D.; Mascola, John R.; Verrips, C. Theo; Strokappe, Nika M.; Rutten, Lucy; McCoy, Laura E.; Weiss, Robin A.; Brown, Corrine S.; Jackson, Raven; Silvestri, Guido; Connors, Mark; Burton, Dennis R.; Shaw, George M.; Nussenzweig, Michel C.; Bjorkman, Pamela J.; Ho, David D.; Farzan, Michael

    2015-01-01

    ABSTRACT Broadly cross-reactive neutralizing antibodies (bNabs) represent powerful tools to combat human immunodeficiency virus type 1 (HIV-1) infection. Here, we examined whether HIV-1-specific bNabs are capable of cross-neutralizing distantly related simian immunodeficiency viruses (SIVs) infecting central (Pan troglodytes troglodytes) (SIVcpzPtt) and eastern (Pan troglodytes schweinfurthii) (SIVcpzPts) chimpanzees (n = 11) as well as western gorillas (Gorilla gorilla gorilla) (SIVgor) (n = 1). We found that bNabs directed against the CD4 binding site (n = 10), peptidoglycans at the base of variable loop 3 (V3) (n = 5), and epitopes at the interface of surface (gp120) and membrane-bound (gp41) envelope glycoproteins (n = 5) failed to neutralize SIVcpz and SIVgor strains. In addition, apex V2-directed bNabs (n = 3) as well as llama-derived (heavy chain only) antibodies (n = 6) recognizing both the CD4 binding site and gp41 epitopes were either completely inactive or neutralized only a fraction of SIVcpzPtt strains. In contrast, one antibody targeting the membrane-proximal external region (MPER) of gp41 (10E8), functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, and CD4-218.3-E51-mim2), as well as mono- and bispecific anti-human CD4 (iMab and LM52) and CCR5 (PRO140, PRO140-10E8) receptor antibodies neutralized >90% of SIVcpz and SIVgor strains with low-nanomolar (0.13 to 8.4 nM) potency. Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5 and neutralized SIVcpz in chimpanzee CD4+ T cells, with 50% inhibitory concentrations (IC50s) ranging from 3.6 to 40.5 nM. These findings provide new insight into the protective capacity of anti-HIV-1 bNabs and identify candidates for further development to combat SIVcpz infection. PMID:25900654

  17. Impact of simian immunodeficiency virus infection on chimpanzee population dynamics.

    PubMed

    Rudicell, Rebecca S; Holland Jones, James; Wroblewski, Emily E; Learn, Gerald H; Li, Yingying; Robertson, Joel D; Greengrass, Elizabeth; Grossmann, Falk; Kamenya, Shadrack; Pintea, Lilian; Mjungu, Deus C; Lonsdorf, Elizabeth V; Mosser, Anna; Lehman, Clarence; Collins, D Anthony; Keele, Brandon F; Goodall, Jane; Hahn, Beatrice H; Pusey, Anne E; Wilson, Michael L

    2010-01-01

    . Together, these results suggest that the decline of the Kalande community was caused, at least in part, by high levels of SIVcpz infection. However, population extinction is not an inevitable consequence of SIVcpz infection, but depends on additional variables, such as migration, that promote survival. These findings are consistent with the uneven distribution of SIVcpz throughout central Africa and explain how chimpanzees in Gombe and elsewhere can be at equipoise with this pathogen. PMID:20886099

  18. Congenital Viral Infections of the Brain: Lessons Learned from Lymphocytic Choriomeningitis Virus in the Neonatal Rat

    PubMed Central

    Bonthius, Daniel J; Perlman, Stanley

    2007-01-01

    The fetal brain is highly vulnerable to teratogens, including many infectious agents. As a consequence of prenatal infection, many children suffer severe and permanent brain injury and dysfunction. Because most animal models of congenital brain infection do not strongly mirror human disease, the models are highly limited in their abilities to shed light on the pathogenesis of these diseases. The animal model for congenital lymphocytic choriomeningitis virus (LCMV) infection, however, does not suffer from this limitation. LCMV is a well-known human pathogen. When the infection occurs during pregnancy, the virus can infect the fetus, and the developing brain is particularly vulnerable. Children with congenital LCMV infection often have substantial neurological deficits. The neonatal rat inoculated with LCMV is a superb model system of human congenital LCMV infection. Virtually all of the neuropathologic changes observed in humans congenitally infected with LCMV, including microencephaly, encephalomalacia, chorioretinitis, porencephalic cysts, neuronal migration disturbances, periventricular infection, and cerebellar hypoplasia, are reproduced in the rat model. Within the developing rat brain, LCMV selectively targets mitotically active neuronal precursors. Thus, the targets of infection and sites of pathology depend on host age at the time of infection. The rat model has further shown that the pathogenic changes induced by LCMV infection are both virus-mediated and immune-mediated. Furthermore, different brain regions simultaneously infected with LCMV can undergo widely different pathologic changes, reflecting different brain region–virus–immune system interactions. Because the neonatal rat inoculated with LCMV so faithfully reproduces the diverse neuropathology observed in the human counterpart, the rat model system is a highly valuable tool for the study of congenital LCMV infection and of all prenatal brain infections In addition, because LCMV induces delayed

  19. Systematic CpT (ApG) depletion and CpG excess are unique genomic signatures of large DNA viruses infecting invertebrates.

    PubMed

    Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal

    2014-01-01

    Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts. PMID:25369195

  20. Systematic CpT (ApG) Depletion and CpG Excess Are Unique Genomic Signatures of Large DNA Viruses Infecting Invertebrates

    PubMed Central

    Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal

    2014-01-01

    Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts. PMID:25369195

  1. Update: Interim Guidance for the Evaluation and Management of Infants with Possible Congenital Zika Virus Infection - United States, August 2016.

    PubMed

    Russell, Kate; Oliver, Sara E; Lewis, Lillianne; Barfield, Wanda D; Cragan, Janet; Meaney-Delman, Dana; Staples, J Erin; Fischer, Marc; Peacock, Georgina; Oduyebo, Titilope; Petersen, Emily E; Zaki, Sherif; Moore, Cynthia A; Rasmussen, Sonja A

    2016-01-01

    CDC has updated its interim guidance for U.S. health care providers caring for infants born to mothers with possible Zika virus infection during pregnancy (1). Laboratory testing is recommended for 1) infants born to mothers with laboratory evidence of Zika virus infection during pregnancy and 2) infants who have abnormal clinical or neuroimaging findings suggestive of congenital Zika syndrome and a maternal epidemiologic link suggesting possible transmission, regardless of maternal Zika virus test results. Congenital Zika syndrome is a recently recognized pattern of congenital anomalies associated with Zika virus infection during pregnancy that includes microcephaly, intracranial calcifications or other brain anomalies, or eye anomalies, among others (2). Recommended infant laboratory evaluation includes both molecular (real-time reverse transcription-polymerase chain reaction [rRT-PCR]) and serologic (immunoglobulin M [IgM]) testing. Initial samples should be collected directly from the infant in the first 2 days of life, if possible; testing of cord blood is not recommended. A positive infant serum or urine rRT-PCR test result confirms congenital Zika virus infection. Positive Zika virus IgM testing, with a negative rRT-PCR result, indicates probable congenital Zika virus infection. In addition to infant Zika virus testing, initial evaluation of all infants born to mothers with laboratory evidence of Zika virus infection during pregnancy should include a comprehensive physical examination, including a neurologic examination, postnatal head ultrasound, and standard newborn hearing screen. Infants with laboratory evidence of congenital Zika virus infection should have a comprehensive ophthalmologic exam and hearing assessment by auditory brainstem response (ABR) testing before 1 month of age. Recommendations for follow-up of infants with laboratory evidence of congenital Zika virus infection depend on whether abnormalities consistent with congenital Zika syndrome

  2. Characterization of host microRNAs that respond to DNA virus infection in a crustacean

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression that are implicated in many processes of eukaryotic cells. It is known that the expression profiles of host miRNAs can be reshaped by viruses. However, a systematic investigation of marine invertebrate miRNAs that respond to virus infection has not yet been performed. Results In this study, the shrimp Marsupenaeus japonicus was challenged by white spot syndrome virus (WSSV). Small RNA sequencing of WSSV-infected shrimp at different time post-infection (0, 6, 24 and 48 h) identified 63 host miRNAs, 48 of which were conserved in other animals, representing 43 distinct families. Of the identified host miRNAs, 31 were differentially expressed in response to virus infection, of which 25 were up-regulated and six down-regulated. The results were confirmed by northern blots. The TargetScan and miRanda algorithms showed that most target genes of the differentially expressed miRNAs were related to immune responses. Gene ontology analysis revealed that immune signaling pathways were mediated by these miRNAs. Evolutionary analysis showed that three of them, miR-1, miR-7 and miR-34, are highly conserved in shrimp, fruit fly and humans and function in the similar pathways. Conclusions Our study provides the first large-scale characterization of marine invertebrate miRNAs that respond to virus infection. This will help to reveal the molecular events involved in virus-host interactions mediated by miRNAs and their evolution in animals. PMID:22545795

  3. Effect of host age on experimental K virus infection in mice.

    PubMed Central

    Greenlee, J E

    1981-01-01

    Mice were inoculated by the oral route with K virus at 4, 8, 12, and 23 days and at 4 months of age. The effect of host age on the pathogenesis of infection was studied by immunofluorescence, virus assay, and histopathology. K virus produced a systemic infection in all animals, although the infection because progressively more limited as animals matured. In mice inoculated at 4 days of age, K virus infection resulted in a fatal interstitial pneumonia identical to that seen in newborn animals and was characterized by the presence of virus and viral antigen in pulmonary and extrapulmonary vascular endothelia, reticuloendothelial organs, and brains. In older animals, K virus infection was clinically inapparent; organ involvement was similar in distribution to that seen in fatally infected suckling ice, but cells exhibiting specific viral fluorescence were fewer in number and viral titers were lower. Although animals surviving K virus infection developed high titers of hemagglutination inhibition antibody to the virus, positive cells and infectious virus could still be detected in intestines 2 months after inoculation. In animals inoculated at 8 and 12 days of age, in which K virus produced an extensive initial infection, virus could also be detected 56 days after inoculation in lungs, livers, spleens, and brains. The present study indicates that murine K virus produces a systemic infection throughout the life of its host and that the maturation of host defenses and the development of specific humoral immunity, although they limit dissemination of virus during acute infection, may not eliminate viral persistence in intestines or other organs once infection has occurred. Images PMID:7263066

  4. Pulmonary immunostimulation with MALP-2 in influenza virus-infected mice increases survival after pneumococcal superinfection.

    PubMed

    Reppe, Katrin; Radünzel, Peter; Dietert, Kristina; Tschernig, Thomas; Wolff, Thorsten; Hammerschmidt, Sven; Gruber, Achim D; Suttorp, Norbert; Witzenrath, Martin

    2015-12-01

    Pulmonary infection with influenza virus is frequently complicated by bacterial superinfection, with Streptococcus pneumoniae being the most prevalent causal pathogen and hence often associated with high morbidity and mortality rates. Local immunosuppression due to pulmonary influenza virus infection has been identified as a major cause of the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza virus infection might improve the host defense against secondary bacterial pathogens. In the present study, we examined the effect of pulmonary immunostimulation with Toll-like receptor 2 (TLR-2)-stimulating macrophage-activating lipopeptide 2 (MALP-2) in influenza A virus (IAV)-infected mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N mice infected with IAV were treated with MALP-2 on day 5 and challenged with S. pneumoniae on day 6. Intratracheal MALP-2 application increased proinflammatory cytokine and chemokine release and enhanced the recruitment of leukocytes, mainly neutrophils, into the alveolar space of IAV-infected mice, without detectable systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected mice 24 h before transnasal pneumococcal infection considerably reduced the bacterial number in the lung tissue without inducing exaggerated inflammation. The pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment of IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared to those of untreated coinfected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection. PMID:26371127

  5. The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection

    PubMed Central

    Traboulsi, Hussein; Cloutier, Alexandre; Boyapelly, Kumaraswamy; Bonin, Marc-André; Marsault, Éric; Cantin, André M.

    2015-01-01

    The host response to influenza virus infection is characterized by an acute lung inflammatory response in which intense inflammatory cell recruitment, hypercytokinemia, and a high level of oxidative stress are present. The sum of these events contributes to the virus-induced lung damage that leads to high a level of morbidity and mortality in susceptible infected patients. In this context, we identified compounds that can simultaneously reduce the excessive inflammatory response and the viral replication as a strategy to treat influenza virus infection. We investigated the anti-inflammatory and antiviral potential activities of isoliquiritigenin (ILG). Interestingly, we demonstrated that ILG is a potent inhibitor of influenza virus replication in human bronchial epithelial cells (50% effective concentration [EC50] = 24.7 μM). In addition, our results showed that this molecule inhibits the expression of inflammatory cytokines induced after the infection of cells with influenza virus. We demonstrated that the anti-inflammatory activity of ILG in the context of influenza virus infection is dependent on the activation of the peroxisome proliferator-activated receptor gamma pathway. Interestingly, ILG phosphate (ILG-p)-treated mice displayed decreased lung inflammation as depicted by reduced cytokine gene expression and inflammatory cell recruitment. We also demonstrated that influenza virus-specific CD8+ effector T cell recruitment was reduced up to 60% in the lungs of mice treated with ILG-p (10 mg/kg) compared to that in saline-treated mice. Finally, we showed that administration of ILG-p reduced lung viral titers and morbidity of mice infected with the PR8/H1N1 virus. PMID:26248373

  6. African Swine Fever Virus Infection in the Argasid Host, Ornithodoros porcinus porcinus

    PubMed Central

    Kleiboeker, S. B.; Burrage, T. G.; Scoles, G. A.; Fish, D.; Rock, D. L.

    1998-01-01

    The pathogenesis of African swine fever virus (ASFV) infection in Ornithodoros porcinus porcinus was examined in nymphal ticks infected with the ASFV isolate Chiredzi/83/1. At times postinfection (p.i.) ranging from 6 h to 290 days, ticks or dissected tick tissues were titrated for virus and examined ultrastructurally for evidence of virus replication. The ASFV infection rate in ticks was 100% in these experiments, and virus infection was not associated with a significant increase in tick mortality. Initial ASFV replication occurred in phagocytic digestive cells of the midgut epithelium. Subsequent infection and replication of ASFV in undifferentiated midgut cells was observed at 15 days p.i. Generalization of virus infection from midgut to other tick tissues required 2 to 3 weeks and most likely involved virus movement across the basal lamina of the midgut into the hemocoel. Secondary sites of virus replication included hemocytes (type I and II), connective tissue, coxal gland, salivary gland, and reproductive tissue. Virus replication was not observed in the nervous tissue of the synganglion, Malpighian tubules, and muscle. Persistent infection, characterized by active virus replication, was observed for all involved tick tissues. After 91 days p.i., viral titers in salivary gland and reproductive tissue were consistently the highest detected. Successful tick-to-pig transmission of ASFV at 48 days p.i. correlated with high viral titers in salivary and coxal gland tissue and their secretions. A similar pattern of virus infection and persistence in O. porcinus porcinus was observed for three additional ASFV tick isolates in their associated ticks. PMID:9499019

  7. Tissue-Protective Effects of NKG2A in Immune-Mediated Clearance of Virus Infection

    PubMed Central

    DeBerge, Matthew P.; Ruby, Jessica A.; Liu, Jun; Schneider, Mark J.; Wang, Yan; Hahn, Young S.; Enelow, Richard I.

    2014-01-01

    Virus infection triggers a CD8+ T cell response that aids in virus clearance, but also expresses effector functions that may result in tissue injury. CD8+ T cells express a variety of activating and inhibiting ligands, though regulation of the expression of inhibitory receptors is not well understood. The ligand for the inhibitory receptor, NKG2A, is the non-classical MHC-I molecule Qa1b, which may also serve as a putative restricting element for the T cell receptors of purported regulatory CD8+ T cells. We have previously shown that Qa1b-null mice suffer considerably enhanced immunopathologic lung injury in the context of CD8+ T cell-mediated clearance of influenza infection, as well as evidence in a non-viral system that failure to ligate NKG2A on CD8+ effector T cells may represent an important component of this process. In this report, we examine the requirements for induction of NKG2A expression, and show that NKG2A expression by CD8+ T cells occurs as a result of migration from the MLN to the inflammatory lung environment, irrespective of peripheral antigen recognition. Further, we confirmed that NKG2A is a mediator in limiting immunopathology in virus infection using mice with a targeted deletion of NKG2A, and infecting the mutants with two different viruses, influenza and adenovirus. In neither infection is virus clearance altered. In influenza infection, the enhanced lung injury was associated with increased chemoattractant production, increased infiltration of inflammatory cells, and significantly enhanced alveolar hemorrhage. The primary mechanism of enhanced injury was the loss of negative regulation of CD8+ T cell effector function. A similar effect was observed in the livers of mutant mice infected intravenously with adenovirus. These results demonstrate the immunoregulatory role of CD8+ NKG2A expression in virus infection, which negatively regulates T cell effector functions and contributes to protection of tissue integrity during virus clearance

  8. Neuropsychological Impact of West Nile Virus Infection: An Extensive Neuropsychiatric Assessment of 49 Cases in Canada

    PubMed Central

    Samaan, Zainab; McDermid Vaz, Stephanie; Bawor, Monica; Potter, Tammy Hlywka; Eskandarian, Sasha; Loeb, Mark

    2016-01-01

    Background West Nile virus emerged as an important human pathogen in North America and continues to pose a risk to public health. It can cause a highly variable range of clinical manifestations ranging from asymptomatic to severe illness. Neuroinvasive disease due to West Nile virus can lead to long-term neurological deficits and psychological impairment. However, these deficits have not been well described. The objective of this study was to characterize the neuropsychological manifestations of West Nile virus infection with a focus on neuroinvasive status and time since infection. Methods Patients from Ontario Canada with a diagnosis of neuroinvasive disease (meningitis, encephalitis, or acute flaccid paralysis) and non-neuroinvasive disease who had participated in a cohort study were enrolled. Clinical and laboratory were collected, as well as demographics and medical history. Cognitive functioning was assessed using a comprehensive battery of neuropsychological tests. Results Data from 49 individuals (32 with West Nile fever and 17 with West Nile neuroinvasive disease) were included in the present cross-sectional analysis. Patterns of neuropsychological impairment were comparable across participants with both neuroinvasive and non-neuroinvasive West Nile virus infection on all cognitive measures. Neuropsychiatric impairment was also observed more frequently at two to four years post-infection compared to earlier stages of illness. Conclusions Our data provide objective evidence for cognitive difficulties among patients who were infected with West Nile virus; these deficits appear to manifest regardless of severity of West Nile virus infection (West Nile fever vs. West Nile neuroinvasive disease), and are more prevalent with increasing illness duration (2–4 years vs. 1 month). Data from this study will help inform patients and healthcare providers about the expected course of recovery, as well as the need to implement effective treatment strategies that

  9. Zika Virus Infection Among U.S. Pregnant Travelers - August 2015-February 2016.

    PubMed

    Meaney-Delman, Dana; Hills, Susan L; Williams, Charnetta; Galang, Romeo R; Iyengar, Preetha; Hennenfent, Andrew K; Rabe, Ingrid B; Panella, Amanda; Oduyebo, Titilope; Honein, Margaret A; Zaki, Sherif; Lindsey, Nicole; Lehman, Jennifer A; Kwit, Natalie; Bertolli, Jeanne; Ellington, Sascha; Igbinosa, Irogue; Minta, Anna A; Petersen, Emily E; Mead, Paul; Rasmussen, Sonja A; Jamieson, Denise J

    2016-03-01

    After reports of microcephaly and other adverse pregnancy outcomes in infants of mothers infected with Zika virus during pregnancy, CDC issued a travel alert on January 15, 2016, advising pregnant women to consider postponing travel to areas with active transmission of Zika virus. On January 19, CDC released interim guidelines for U.S. health care providers caring for pregnant women with travel to an affected area, and an update was released on February 5. As of February 17, CDC had received reports of nine pregnant travelers with laboratory-confirmed Zika virus disease; 10 additional reports of Zika virus disease among pregnant women are currently under investigation. No Zika virus-related hospitalizations or deaths among pregnant women were reported. Pregnancy outcomes among the nine confirmed cases included two early pregnancy losses, two elective terminations, and three live births (two apparently healthy infants and one infant with severe microcephaly); two pregnancies (approximately 18 weeks' and 34 weeks' gestation) are continuing without known complications. Confirmed cases of Zika virus infection were reported among women who had traveled to one or more of the following nine areas with ongoing local transmission of Zika virus: American Samoa, Brazil, El Salvador, Guatemala, Haiti, Honduras, Mexico, Puerto Rico, and Samoa. This report summarizes findings from the nine women with confirmed Zika virus infection during pregnancy, including case reports for four women with various clinical outcomes. U.S. health care providers caring for pregnant women with possible Zika virus exposure during pregnancy should follow CDC guidelines for patient evaluation and management. Zika virus disease is a nationally notifiable condition. CDC has developed a voluntary registry to collect information about U.S. pregnant women with confirmed Zika virus infection and their infants. Information about the registry is in preparation and will be available on the CDC website. PMID

  10. Pulmonary Immunostimulation with MALP-2 in Influenza Virus-Infected Mice Increases Survival after Pneumococcal Superinfection

    PubMed Central

    Reppe, Katrin; Radünzel, Peter; Dietert, Kristina; Tschernig, Thomas; Wolff, Thorsten; Hammerschmidt, Sven; Gruber, Achim D.; Suttorp, Norbert

    2015-01-01

    Pulmonary infection with influenza virus is frequently complicated by bacterial superinfection, with Streptococcus pneumoniae being the most prevalent causal pathogen and hence often associated with high morbidity and mortality rates. Local immunosuppression due to pulmonary influenza virus infection has been identified as a major cause of the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza virus infection might improve the host defense against secondary bacterial pathogens. In the present study, we examined the effect of pulmonary immunostimulation with Toll-like receptor 2 (TLR-2)-stimulating macrophage-activating lipopeptide 2 (MALP-2) in influenza A virus (IAV)-infected mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N mice infected with IAV were treated with MALP-2 on day 5 and challenged with S. pneumoniae on day 6. Intratracheal MALP-2 application increased proinflammatory cytokine and chemokine release and enhanced the recruitment of leukocytes, mainly neutrophils, into the alveolar space of IAV-infected mice, without detectable systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected mice 24 h before transnasal pneumococcal infection considerably reduced the bacterial number in the lung tissue without inducing exaggerated inflammation. The pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment of IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared to those of untreated coinfected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection. PMID:26371127

  11. A new reportable disease is born: Taiwan Centers for Disease Control's response to emerging Zika virus infection.

    PubMed

    Huang, Angela Song-En; Shu, Pei-Yun; Yang, Chin-Hui

    2016-04-01

    Zika virus infection, usually a mild disease transmitted through the bite of Aedes mosquitos, has been reported to be possibly associated with microcephaly and neurologic complications. Taiwan's first imported case of Zika virus infection was found through fever screening at airport entry in January 2016. No virus was isolated from patient's blood taken during acute illness; however, PCR products showed that the virus was of Asian lineage closely related to virus from Cambodia. To prevent Zika virus from spreading in Taiwan, the Taiwan Centers for Disease Control has strengthened efforts in quarantine and surveillance, increased Zika virus infection diagnostic capacity, implemented healthcare system preparedness plans, and enhanced vector control program through community mobilization and education. Besides the first imported case, no additional cases of Zika virus infection have been identified. Furthermore, no significant increase in the number of microcephaly or Guillain- Barré Syndrome has been observed in Taiwan. To date, there have been no autochthonous transmissions of Zika virus infection. PMID:27013110

  12. IL-1β and IL-6 Upregulation in Children with H1N1 Influenza Virus Infection

    PubMed Central

    Chiaretti, Antonio; Pulitanò, Silvia; Barone, Giovanni; Ferrara, Pietro; Capozzi, Domenico; Riccardi, Riccardo

    2013-01-01

    The role of cytokines in relation to clinical manifestations, disease severity, and outcome of children with H1N1 virus infection remains thus far unclear. The aim of this study was to evaluate interleukin IL-1β and IL-6 plasma expressions and their association with clinical findings, disease severity, and outcome of children with H1N1 infection. We prospectively evaluated 15 children with H1N1 virus infection and 15 controls with lower respiratory tract infections (LRTI). Interleukin plasma levels were measured using immunoenzymatic assays. Significantly higher levels of IL-1β and IL-6 were detected in all patients with H1N1 virus infection compared to controls. It is noteworthy to mention that in H1N1 patients with more severe clinical manifestations of disease IL-1β and IL-6 expressions were significantly upregulated compared to H1N1 patients with mild clinical manifestations. In particular, IL-6 was significantly correlated with specific clinical findings, such as severity of respiratory compromise and fever. No correlation was found between interleukin expression and final outcome. In conclusion, H1N1 virus infection induces an early and significant upregulation of both interleukins IL1β and IL-6 plasma expressions. The upregulation of these cytokines is likely to play a proinflammatory role in H1N1 virus infection and may contribute to airway inflammation and bronchial hyperreactivity in these patients. PMID:23737648

  13. Optical diagnosis of dengue virus infection in human blood serum using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Saleem, M.; Bilal, M.; Anwar, S.; Rehman, A.; Ahmed, M.

    2013-03-01

    We present the optical diagnosis of dengue virus infection in human blood serum using Raman spectroscopy. Raman spectra were acquired from 18 blood serum samples using a laser at 532 nm as the excitation source. A multivariate regression model based on partial least-squares regression is developed that uses Raman spectra to predict dengue infection with leave-one-sample-out cross validation. The prediction of dengue infection by our model yields correlation coefficient r2 values of 0.9998 between the predicted and reference clinical results. The model was tested for six unknown human blood sera and found to be 100% accurate in accordance with the clinical results.

  14. Dengue virus infection in renal allograft recipients: a case series during 2010 outbreak.

    PubMed

    Prasad, N; Bhadauria, D; Sharma, R K; Gupta, A; Kaul, A; Srivastava, A

    2012-04-01

    Dengue virus infection is an emerging global threat caused by Arbovirus, a virus from Flaviridiae family, which is transmitted by mosquitoes, Aedes aegypti and Aedes albopictus. Renal transplant recipients who live in the endemic zones of dengue infection or who travel to an endemic zone could be at risk of this infection. Despite multiple epidemics and a high case fatality rate in the Southeast Asian region, only a few cases of dengue infection in renal transplant recipients have been reported. Here, we report a case series of 8 dengue viral infection in renal transplant recipients. Of the 8 patients, 3 developed dengue hemorrhagic shock syndrome and died. PMID:22212524

  15. A rare case of verrucous carcinoma of penis in an human immunodeficiency virus- infected patient

    PubMed Central

    Noronha, Tonita Mariola; Girisha, Banavasi S.; Bhat, Shubha P.; Christy, Carol M.; Handattu, Sripathi; Fernandes, Michelle S.

    2015-01-01

    Cancer is a significant cause of morbidity and mortality in human immunodeficiency virus-infected subjects. Verrucous carcinoma is a peculiarly slow evolving, but relentlessly expanding variant of epidermoid carcinoma that is extremely reluctant to metastasize. A 60-year-old unmarried male patient presented with urethral discharge of 3 weeks duration. Dorsal slit of the prepuce revealed an ulceroproliferative growth measuring 3 cm × 3 cm arising from prepuce and involving glans. Biopsy from the growth in the prepuce showed histopathological features of verrucous carcinoma. Partial amputation of the penis was done. Human papillomavirus DNA by polymerase chain reaction was negative. The patient was started on antiretroviral therapy. PMID:26692616

  16. Serum Ferritin as a Predictor of Host Response to Hepatitis B Virus Infection

    NASA Astrophysics Data System (ADS)

    Lustbader, Edward D.; Hann, Hie-Won L.; Blumberg, Baruch S.

    1983-04-01

    With hemodialysis patients, a high serum ferritin before there was serological evidence of hepatitis B virus infection increased the likelihood that the infection would be persistent. This finding suggested that hepatitis B virus is likely to infect and actively replicate in liver cells with the propensity for increased ferritin synthesis. The virus itself could stimulate the synthesis of ferritin in a cyclic positive feedback mechanism that increases intracellular ferritin concentration and, eventually, intracellular iron. Transformed liver cells have low iron content, do not replicate hepatitis B virus, and require iron for growth. Infected, nonmalignant liver cells could supply iron to the transformed cells and nourish their expansion.

  17. Regulation of apoptosis in African swine fever virus-infected macrophages.

    PubMed

    Zsak, Laszlo; Neilan, John G

    2002-05-01

    A number of viruses have evolved antiapoptotic mechanisms to promote infected-cell survival, either to ensure efficient productive viral replication or to promote long-term survival of virus-infected cells. Recent studies identified critical African swine fever virus genes involved in the complex regulation of ASFV-host interactions. Here we review the present knowledge of the recently identified ASFV genes with special attention to those which affect viral virulence, host range, and pathogenesis by regulating viral-induced apoptotic mechanisms. PMID:12805900

  18. Virtual screen for repurposing approved and experimental drugs for candidate inhibitors of EBOLA virus infection

    PubMed Central

    Veljkovic, Veljko; Loiseau, Philippe M.; Figadere, Bruno; Glisic, Sanja; Veljkovic, Nevena; Perovic, Vladimir R.; Cavanaugh, David P.; Branch, Donald R.

    2015-01-01

    The ongoing Ebola virus epidemic has presented numerous challenges with respect to control and treatment because there are no approved drugs or vaccines for the Ebola virus disease (EVD). Herein is proposed simple theoretical criterion for fast virtual screening of molecular libraries for candidate inhibitors of Ebola virus infection. We performed a repurposing screen of 6438 drugs from DrugBank using this criterion and selected 267 approved and 382 experimental drugs as candidates for treatment of EVD including 15 anti-malarial drugs and 32 antibiotics. An open source Web server allowing screening of molecular libraries for candidate drugs for treatment of EVD was also established. PMID:25717373

  19. Toxic epidermal necrolysis caused by fluconazole in a patient with human immunodeficiency virus infection.

    PubMed

    George, Jacob; Sharma, Arun; Dixit, Ramakant; Chhabra, Naveen; Sharma, Smita

    2012-07-01

    Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are rare but serious dermatologic disorders. These grave conditions present as medical emergency, requiring prompt diagnosis and management. These are often drug induced and various groups of drugs, such as sulfa drugs, NSAIDS, etc., have been implicated as to cause TEN. Fluconazole is a commonly used drug with mild side effects. TEN caused by fluconazole is rare, and till now only few cases have been reported in the literature. We present a case of TEN in a human immunodeficiency virus infected man following fluconazole therapy in view of its rare occurrence. PMID:23129968

  20. Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection

    PubMed Central

    2015-01-01

    Recently, we reported that chlorcyclizine (CCZ, Rac-2), an over-the-counter antihistamine piperazine drug, possesses in vitro and in vivo activity against hepatitis C virus. Here, we describe structure–activity relationship (SAR) efforts that resulted in the optimization of novel chlorcyclizine derivatives as anti-HCV agents. Several compounds exhibited EC50 values below 10 nM against HCV infection, cytotoxicity selectivity indices above 2000, and showed improved in vivo pharmacokinetic properties. The optimized molecules can serve as lead preclinical candidates for the treatment of hepatitis C virus infection and as probes to study hepatitis C virus pathogenesis and host–virus interaction. PMID:26599718

  1. Extensive molluscum contagiosum virus infection in a young adult receiving fingolimod.

    PubMed

    Behle, Valeria; Wobser, Marion; Goebeler, Matthias; Stoevesandt, Johanna

    2016-06-01

    Fingolimod-related viral infections have been described on several occasions since its introduction in 2010. We hereby add a report on an otherwise immunocompetent, 18-year old Caucasian man with relapsing-remitting multiple sclerosis who developed a protracted and extensive molluscum contagiosum (MC) virus infection shortly after being started on fingolimod. Wide-spread cutaneous MC infections in adult patients are considered indicative of underlying immunosuppression. Neurologists prescribing fingolimod ought to be aware of a possibly increased risk of MC, but also need to know about its relative benignity, lack of extra-cutaneous complications, and adequate treatment options. PMID:26860987

  2. The Use of Humanized Monoclonal Antibodies for the Prevention of Respiratory Syncytial Virus Infection

    PubMed Central

    Arcuri, Santo; Galletti, Silvia; Faldella, Giacomo

    2013-01-01

    Monoclonal antibodies are widely used both in infants and in adults for several indications. Humanized monoclonal antibodies (palivizumab) have been used for many years for the prevention of respiratory syncytial virus infection in pediatric populations (preterm infants, infants with chronic lung disease or congenital heart disease) at high risk of severe and potentially lethal course of the infection. This drug was reported to be safe, well tolerated and effective to decrease the hospitalization rate and mortality in these groups of infants by several clinical trials. In the present paper we report the development and the current use of monoclonal antibodies for prophylaxis against respiratory syncytial virus. PMID:23840240

  3. [Non Hodgkin's lymphoma and chronic hepatitis C virus infection: a non-fortuitous association. Two case reports].

    PubMed

    Kallel, Sana; Essid, Mejda; Boujelbene, Salah; Ben Brahim, Ihsen; Chatty, Samia; Sassi, Sadok; Azzouz, Moussadek

    2007-08-01

    Many authors suggest the role of hepatitis C virus (HCV) infection in the pathology of B-cell non Hodgkin's lymphomas; this is based on epidemiological, physiopathological and therapeutic arguments. The frequency of the association with hepatitis C virus infection is variable in the different study (1 to 30%). We report two cases of hepatitis C virus infection in association with non Hodgkin's lymphomas. The first case presented a low grad splenic and nodal non-Hodgkin's lymphoma associated with hepatitis C virus infection and complicated by hepato-cellular carcinoma. The second case presented a high grad nodal non-Hodgkin's lymphoma associated with HCV infection. Our cases report confirms the hypothesis of a key role of hepatitis C virus in the pathogenesis of B-cell lymphoproliferative disorders and in particular the non-Hodgkin's lymphoma. Although of several hypothesis concerning the ethiopathogenic mechanisms of this association, new studies will necessary to improve the real mechanism of this association PMID:18254295

  4. A sero-survey of subtype H3 influenza A virus infection in dogs and cats in Japan.

    PubMed

    Said, Awlad Wadair Ali; Usui, Tatsufumi; Shinya, Kyoko; Ono, Etsuro; Ito, Toshihiro; Hikasa, Yoshiaki; Matsuu, Aya; Takeuchi, Takashi; Sugiyama, Akihiko; Nishii, Naohito; Yamaguchi, Tsuyoshi

    2011-04-01

    A sero-epidemiological survey of human and equine H3 influenza A virus infections in dogs and cats using the hemagglutination inhibition (HI) and neuraminidase inhibition (NI) tests was conducted. Serum samples were collected from 582 dogs and 237 cats in Japan during the periods 2002-2008 and 1997-2008, respectively. Although no HI antibodies against equine H3 virus were detected, 9 (3.8%) from cats and 12 (2.1%) from dogs were HI-positive against human H3 virus. Only one serum each from dogs and cats was NI-positive against N2 virus. These findings suggest that although equine H3 influenza virus infections have not been prevalent in companion animals, human H3N2 influenza A virus infections have occurred in dogs and cats in recent years in Japan. PMID:21150133

  5. Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles.

    PubMed

    Bimbo, Luis M; Denisova, Oxana V; Mäkilä, Ermei; Kaasalainen, Martti; De Brabander, Jef K; Hirvonen, Jouni; Salonen, Jarno; Kakkola, Laura; Kainov, Denis; Santos, Hélder A

    2013-08-27

    Influenza A viruses (IAVs) cause recurrent epidemics in humans, with serious threat of lethal worldwide pandemics. The occurrence of antiviral-resistant virus strains and the emergence of highly pathogenic influenza viruses have triggered an urgent need to develop new anti-IAV treatments. One compound found to inhibit IAV, and other virus infections, is saliphenylhalamide (SaliPhe). SaliPhe targets host vacuolar-ATPase and inhibits acidification of endosomes, a process needed for productive virus infection. The major obstacle for the further development of SaliPhe as antiviral drug has been its poor solubility. Here, we investigated the possibility to increase SaliPhe solubility by loading the compound in thermally hydrocarbonized porous silicon (THCPSi) nanoparticles. SaliPhe-loaded nanoparticles were further investigated for the ability to inhibit influenza A infection in human retinal pigment epithelium and Madin-Darby canine kidney cells, and we show that upon release from THCPSi, SaliPhe inhibited IAV infection in vitro and reduced the amount of progeny virus in IAV-infected cells. Overall, the PSi-based nanosystem exhibited increased dissolution of the investigated anti-IAV drug SaliPhe and displayed excellent in vitro stability, low cytotoxicity, and remarkable reduction of viral load in the absence of organic solvents. This proof-of-principle study indicates that PSi nanoparticles could be used for efficient delivery of antivirals to infected cells. PMID:23889734

  6. Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks.

    PubMed

    Haque, Azizul; Hober, Didier; Blondiaux, Joel

    2015-10-01

    Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients. PMID:26248374

  7. Changes in autophagic response in patients with chronic hepatitis C virus infection.

    PubMed

    Rautou, Pierre-Emmanuel; Cazals-Hatem, Dominique; Feldmann, Gérard; Mansouri, Abdellah; Grodet, Alain; Barge, Sandrine; Martinot-Peignoux, Michèle; Duces, Aurélie; Bièche, Ivan; Lebrec, Didier; Bedossa, Pierre; Paradis, Valérie; Marcellin, Patrick; Valla, Dominique; Asselah, Tarik; Moreau, Richard

    2011-06-01

    Autophagy is a regulated process that can be involved in the elimination of intracellular microorganisms and in antigen presentation. Some in vitro studies have shown an altered autophagic response in hepatitis C virus infected hepatocytes. The present study aimed at evaluating the autophagic process in the liver of chronic hepatitis C (CHC) patients. Fifty-six CHC patients and 47 control patients (8 with nonalcoholic steatohepatitis or alcoholic liver disease, 18 with chronic heptatitis B virus infection, and 21 with no or mild liver abnormalities at histological examination) were included. Autophagy was assessed by means of electron microscopy and microtubule-associated protein light chain 3 immunoblotting. Using light chain 3 immunoblotting, the form present on autophagic vesicle (light chain 3-II) was significantly higher in CHC patients than in controls (P < 0.05). Using quantitative electron microscopy analysis, the median number of autophagic vesicles observed in hepatocytes from CHC patients was sixfold higher than in overall controls (P < 0.001). In contrast, there was no difference between CHC patients and controls in the number of mature lysosomes with electron-dense contents arguing in favor of a lack of fusion between autophagosome and lysosome. Neither genotype nor viral load influenced the autophagy level. In conclusion, autophagy is altered in hepatocytes from CHC patients, likely due to a blockade of the last step of the autophagic process. PMID:21641393

  8. Balancing viral replication in spleen and liver determines the outcome of systemic virus infection.

    PubMed

    Lang, K S; Lang, P A

    2015-12-01

    The innate immune system limits virus replication during systemic infection by producing type I interferons (IFN-I) but still has to allow viral replication to achieve maximal innate and adaptive immune activation. Some spleen and lymph node resident antigen presenting cells (APCs) show limited response to IFN-I due to expression of the endogenous inhibitor of IFN-I signaling, Usp18. Therefore, virus in this spleen niche replicates despite high levels of IFN-I. This enforced viral replication leads to an exorbitant propagation of viral antigens and viral RNA. Viral antigen leads to massive activation of the adaptive immune system, while viral RNA to activated innate immunity. In contrast to these APCs, liver resident Kupffer cells, take up most of the systemic virus and suppress its replication in response to IFN-I. In addition, virus specific CD8 + T cells which are primed in the spleen migrate to the liver and kill virus infected cells. In this review we discuss the different mechanisms, which influence immune activation in spleen and antiviral mechanisms in the liver and how they determine the outcome of virus infection. PMID:26666281

  9. Experimental biology and pathogenesis of Junin virus infection in animals and man*

    PubMed Central

    Weissenbacher, M. C.; De Guerrero, L. B.; Boxaca, M. C.

    1975-01-01

    A fatal disease resembling Argentine haemorrhagic fever of man has been produced in guinea-pigs and mice by inoculation with Junin virus. Infected guinea-pigs show macroscopic and microscopic haemorrhagic lesions, marked bone marrow changes, decreased leukocytes and platelets in the peripheral blood, and impairment of immunological response. This response permits differentiation between pathogenic (XJ) and attenuated (XJ Cl3) strains. Guinea-pigs inoculated with the XJ Cl3 strain develop an inapparent infection accompanied by slight haematological changes, the appearance of antibody, and protection against challenge with the pathogenic strain. The attenuated strain has been used successfully as an immunizing antigen in 636 human volunteers. Guinea-pigs infected with Tacaribe virus show cross-protection against Junin virus, with the presence of heterologous neutralizing antibodies. Suckling mice infected with Junin virus develop a typical viral encephalitis; the pathogenicity of the virus decreases with increasing age of the mice. Experiments with thymectomized mice and with mice treated with antithymocyte serum suggest that the pathogenicity of Junin virus in this host is related to the integrity of the thymus-dependent immune system. There is evidence that humoral antibodies do not play any role in the development of the encephalitic lesions but rather protect mice against Junin virus infection. A recent serological survey among laboratory workers and inhabitants of the endemic area has demonstrated the presence of inapparent infection with Junin virus. PMID:182401

  10. Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks

    PubMed Central

    Hober, Didier; Blondiaux, Joel

    2015-01-01

    Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients. PMID:26248374

  11. Development of a preventive vaccine for Ebola virus infection in primates.

    PubMed

    Sullivan, N J; Sanchez, A; Rollin, P E; Yang, Z Y; Nabel, G J

    2000-11-30

    Outbreaks of haemorrhagic fever caused by the Ebola virus are associated with high mortality rates that are a distinguishing feature of this human pathogen. The highest lethality is associated with the Zaire subtype, one of four strains identified to date. Its rapid progression allows little opportunity to develop natural immunity, and there is currently no effective anti-viral therapy. Therefore, vaccination offers a promising intervention to prevent infection and limit spread. Here we describe a highly effective vaccine strategy for Ebola virus infection in non-human primates. A combination of DNA immunization and boosting with adenoviral vectors that encode viral proteins generated cellular and humoral immunity in cynomolgus macaques. Challenge with a lethal dose of the highly pathogenic, wild-type, 1976 Mayinga strain of Ebola Zaire virus resulted in uniform infection in controls, who progressed to a moribund state and death in less than one week. In contrast, all vaccinated animals were asymptomatic for more than six months, with no detectable virus after the initial challenge. These findings demonstrate that it is possible to develop a preventive vaccine against Ebola virus infection in primates. PMID:11117750

  12. Chikungunya Virus Infections Among Travelers–United States, 2010–2013

    PubMed Central

    Lindsey, Nicole P.; Prince, Harry E.; Kosoy, Olga; Laven, Janeen; Messenger, Sharon; Staples, J. Erin; Fischer, Marc

    2015-01-01

    Chikungunya virus is an emerging threat to the United States because humans are amplifying hosts and competent mosquito vectors are present in many regions of the country. We identified laboratory-confirmed chikungunya virus infections with diagnostic testing performed in the United States from 2010 through 2013. We described the epidemiology of these cases and determined which were reported to ArboNET. From 2010 through 2013, 115 laboratory-confirmed chikungunya virus infections were identified. Among 55 cases with known travel history, 53 (96%) reported travel to Asia and 2 (4%) to Africa. No locally-acquired infections were identified. Six patients had detectable viremia after returning to the United States. Only 21% of identified cases were reported to ArboNET, with a median of 72 days between illness onset and reporting. Given the risk of introduction into the United States, healthcare providers and public health officials should be educated about the recognition, diagnosis, and timely reporting of chikungunya virus disease cases. PMID:25349374

  13. Clinical and pathologic features of West Nile virus infection in native North American owls (Family strigidae).

    PubMed

    Fitzgerald, S D; Patterson, J S; Kiupel, M; Simmons, H A; Grimes, S D; Sarver, C F; Fulton, R M; Steficek, B A; Cooley, T M; Massey, J P; Sikarskie, J G

    2003-01-01

    Since the initial report of West Nile virus in the northeastern United States in 1999, the virus has spread rapidly westward and southward across the country. In the summer of 2002, several midwestern states reported increased cases of neurologic disease and mortality associated with West Nile virus infection in various native North American owl species. This report summarizes the clinical and pathologic findings for 13 captive and free-ranging owls. Affected species were all in the family Strigidae and included seven snowy owls (Nyctea scandiaca), four great-horned owls (Bubo virginianus), a barred owl (Strix varia), and a short-eared owl (Asio flammeus). Neurologic signs identified included head tilt, uncoordinated flight, paralysis, tremors, and seizures. Owls that died were screened for flaviviral proteins by immunohistochemical staining of formalin-fixed tissues, followed by specific polymerase chain reaction assay to confirm West Nile virus with fresh tissues when available. Microscopic lesions were widespread, involving brain, heart, liver, kidney, and spleen, and were typically nonsuppurative with infiltration by predominantly lymphocytes and plasma cells. Lesions in owls were much more severe than those previously reported in corvids such as crows, which are considered highly susceptible to infection and are routinely used as sentinel species for monitoring for the presence and spread of West Nile virus. This report is the first detailed description of the pathology of West Nile virus infection in Strigiformes and indicates that this bird family is susceptible to natural infection with West Nile virus. PMID:14562887

  14. Changes in Autophagic Response in Patients with Chronic Hepatitis C Virus Infection

    PubMed Central

    Rautou, Pierre-Emmanuel; Cazals-Hatem, Dominique; Feldmann, Gérard; Mansouri, Abdellah; Grodet, Alain; Barge, Sandrine; Martinot-Peignoux, Michèle; Duces, Aurélie; Bièche, Ivan; Lebrec, Didier; Bedossa, Pierre; Paradis, Valérie; Marcellin, Patrick; Valla, Dominique; Asselah, Tarik; Moreau, Richard

    2011-01-01

    Autophagy is a regulated process that can be involved in the elimination of intracellular microorganisms and in antigen presentation. Some in vitro studies have shown an altered autophagic response in hepatitis C virus infected hepatocytes. The present study aimed at evaluating the autophagic process in the liver of chronic hepatitis C (CHC) patients. Fifty-six CHC patients and 47 control patients (8 with nonalcoholic steatohepatitis or alcoholic liver disease, 18 with chronic heptatitis B virus infection, and 21 with no or mild liver abnormalities at histological examination) were included. Autophagy was assessed by means of electron microscopy and microtubule-associated protein light chain 3 immunoblotting. Using light chain 3 immunoblotting, the form present on autophagic vesicle (light chain 3-II) was significantly higher in CHC patients than in controls (P < 0.05). Using quantitative electron microscopy analysis, the median number of autophagic vesicles observed in hepatocytes from CHC patients was sixfold higher than in overall controls (P < 0.001). In contrast, there was no difference between CHC patients and controls in the number of mature lysosomes with electron-dense contents arguing in favor of a lack of fusion between autophagosome and lysosome. Neither genotype nor viral load influenced the autophagy level. In conclusion, autophagy is altered in hepatocytes from CHC patients, likely due to a blockade of the last step of the autophagic process. PMID:21641393

  15. A portable approach for the surveillance of dengue virus-infected mosquitoes.

    PubMed

    Muller, David A; Frentiu, Francesca D; Rojas, Alejandra; Moreira, Luciano A; O'Neill, Scott L; Young, Paul R

    2012-07-01

    Dengue virus is the most significant human viral pathogen spread by the bite of an infected mosquito. With no vaccine or antiviral therapy currently available, disease prevention relies largely on surveillance and mosquito control. Preventing the onset of dengue outbreaks and effective vector management would be considerably enhanced through surveillance of dengue virus prevalence in natural mosquito populations. However, current approaches to the identification of virus in field-caught mosquitoes require relatively slow and labor intensive techniques such as virus isolation or RT-PCR involving specialized facilities and personnel. A rapid and portable method for detecting dengue virus-infected mosquitoes is described. Using a hand held battery operated homogenizer and a dengue diagnostic rapid strip the viral protein NS1 was detected as a marker of dengue virus infection. This method could be performed in less than 30 min in the field, requiring no downstream processing, and is able to detect a single infected mosquito in a pool of at least 50 uninfected mosquitoes. The method described in this study allows rapid, real-time monitoring of dengue virus presence in mosquito populations and could be a useful addition to effective monitoring and vector control responses. PMID:22575689

  16. Shifts in Buchnera aphidicola density in soybean aphids (Aphis glycines) feeding on virus-infected soybean.

    PubMed

    Cassone, Bryan J; Redinbaugh, Margaret G; Dorrance, Anne E; Michel, Andrew P

    2015-08-01

    Vertically transmitted bacterial symbionts are common in arthropods. Aphids undergo an obligate symbiosis with Buchnera aphidicola, which provides essential amino acids to its host and contributes directly to nymph growth and reproduction. We previously found that newly adult Aphis glycines feeding on soybean infected with the beetle-transmitted Bean pod mottle virus (BPMV) had significantly reduced fecundity. We hypothesized that the reduced fecundity was attributable to detrimental impacts of the virus on the aphid microbiome, namely Buchnera. To test this, mRNA sequencing and quantitative real-time PCR were used to assay Buchnera transcript abundance and titre in A. glycines feeding on Soybean mosaic virus-infected, BPMV-infected, and healthy soybean for up to 14 days. Our results indicated that Buchnera density was lower and ultimately suppressed in aphids feeding on virus-infected soybean. While the decreased Buchnera titre may be associated with reduced aphid fecundity, additional mechanisms are probably involved. The present report begins to describe how interactions among insects, plants, and plant pathogens influence endosymbiont population dynamics. PMID:25845267

  17. Review on the impact of pregnancy and obesity on influenza virus infection

    PubMed Central

    Karlsson, Erik A.; Marcelin, Glendie; Webby, Richard J.; Schultz‐Cherry, Stacey

    2012-01-01

    Please cite this paper as: Karlsson et al. (2012) Review on the impact of pregnancy and obesity on influenza virus infection. Influenza and Other Respiratory Viruses 6(6), 449–460. A myriad of risk factors have been linked to an increase in the severity of the pandemic H1N1 2009 influenza A virus [A(H1N1)pdm09] including pregnancy and obesity where death rates can be elevated as compared to the general population. The goal of this review is to provide an overview of the influence of pregnancy and obesity on the reported cases of A(H1N1)pdm09 virus infection and of how the concurrent presence of these factors may have an exacerbating effect on infection outcome. Also, the hypothesized immunologic mechanisms that contribute to A(H1N1)pdm09 virus severity during pregnant or obese states are outlined. Identifying the mechanisms underlying the increased disease severity in these populations may result in improved therapeutic approaches and future pandemic preparedness. PMID:22335790

  18. The use of FTIR microscopy for evaluation of herpes viruses infection development kinetics

    NASA Astrophysics Data System (ADS)

    Erukhimovitch, Vitaly; Mukmanov, Igor; Talyshinsky, Marina; Souprun, Yelena; Huleihel, Mahmoud

    2004-08-01

    The kinetics of Herpes simplex infection development was studied using an FTIR microscopy (FTIR-M) method. The family of herpes viruses includes several members like H. simplex types I and II (HSV I, II), Varicella zoster (VZV) viruses which are involved in various human and animal infections of different parts of the body. In our previous study, we found significant spectral differences between normal uninfected cells in cultures and cells infected with herpes viruses at early stages of the infection. In the present study, cells in cultures were infected with either HSV-I or VZV and at various times post-infection they were examined either by optical microscopy or by advanced FTIR-M. Spectroscopic measurements show a consistent decrease in the intensity of the carbohydrate peak in correlation with the viral infection development, observed by optical microscopy. This decrease in cellular carbohydrate level was used as indicator for herpes viruses infection kinetics. This parameter could be used as a basis for applying a spectroscopic method for the evaluation of herpes virus infection development. Our results show also that the development kinetics of viral infection has an exponential character for these viruses.

  19. Seroepidemiological Evidence of Subtype H3N8 Influenza Virus Infection among Pet Dogs in China

    PubMed Central

    Zhou, Pei; Huang, San; Zeng, Weijie; Zhang, Xin; Wang, Lifang; Fu, Xinliang; Li, Shoujun

    2016-01-01

    The H3N8 virus and the H3N2 virus are the main subtypes of canine influenza virus (CIV). H3N8 CIV mainly circulates in America, and H3N2 CIV mainly circulates in Asia. However, there was an outbreak of the Asian H3N2 virus in the United States (US) in 2015. Thus, it is important to evaluate the presence of subtype H3N8 virus in dogs in China. From May 2015 to November 2015, 600 sera from pet dogs were collected from Guangzhou, Shanghai, Beijing and Shenzhen for hemagglutination inhibition (HI) assays and microneutralization (MN) assays. Fifty-two (8.66%) of the 600 sera were positive for the subtype H3N2 virus, which matched the previous reports. Five (0.83%) of 600 sera were positive for the subtype H3N8 virus (H3N8 EIV or H3N8 AIV or H3N8 CIV), which is the first report of subtype H3N8 virus infection among dogs in China and remind us to play more attention to this subtype virus. Therefore, further serological and virological surveillance of influenza virus infection among dogs in China is imperative. PMID:27414031

  20. In vitro and in vivo inhibitory effects of disodium cromoglycate on influenza virus infection.

    PubMed

    Hidari, Kazuya I P J; Tsujii, Eisaku; Hiroi, Jun; Mano, Eriko; Miyatake, Akihiko; Miyamoto, Daisei; Suzuki, Takashi; Suzuki, Yasuo

    2004-06-01

    Disodium cromoglycate (DSCG) is one of the safest drugs for the prevention of bronchial asthma and allergic rhinitis attacks. The effect of DSCG on acute upper respiratory tract viral infection is still controversial. Here we investigated DSCG inhibition of influenza virus infection in vivo and in vitro. In vivo effects of DSCG on viral infection were assessed using a murine model of respiratory tract infection. Intranasal administration of DSCG protected mice from death induced by infection with influenza virus A/PR/8/34. We analyzed DSCG anti-viral effects in vitro by either (i) treating cells prior to viral adsorption, (ii) treating cells concurrently with viral adsorption, or (iii) treating cells after viral adsorption. DSCG treatment of cells during or after, but not before, viral adsorption significantly inhibited influenza viral infection, indicating DSCG acts on events late in viral infection. DSCG exerts anti-influenza effect both in vitro and in vivo at the doses compatible with treatment for asthma. DSCG marginally inhibited influenza viral neuraminidase and membrane fusion functions, suggesting that DSCG inhibition of viral neuraminidase and fusion activities may partially mediate this anti-influenza effect. Our results indicate that treatment of patients including children with DSCG may take advantages for prevention from influenza virus infection. PMID:15187427

  1. Micro-Raman spectroscopy study of ALVAC virus infected chicken embryo cells

    NASA Astrophysics Data System (ADS)

    Misra, Anupam K.; Kamemoto, Lori E.; Hu, Ningjie; Dykes, Ava C.; Yu, Qigui; Zinin, Pavel V.; Sharma, Shiv K.

    2011-05-01

    Micro- Raman spectroscopic investigation of ALVAC virus and of normal chicken embryo fibroblast cells and the cells infected with ALVAC virus labeled with green fluorescence protein (GFP) were performed with a 785 nm laser. Good quality Micro-Raman spectra of the Alvac II virus were obtained. These spectra show that the ALVAC II virus contains buried tyrosine residues and the coat protein of the virus has α-helical structure. A comparison of Raman spectra of normal and virus infected chicken embryo fibroblast cells revealed that the virus infected cells show additional bands at 535, 928, and 1091 cm-1, respectively, corresponding to δ(C-O-C) glycosidic ring, protein α-helix, and DNA (O-P-O) modes. In addition, the tyrosine resonance double (833 and 855 cm-1) shows reversal in the intensity of the higher-frequency band as compared to the normal cells that can be used to identify the infected cells. In the C-H stretching region, the infected cells show bands with higher intensity as compared to that of the corresponding bands in the normal cells. We also found that the presence of GFP does not affect the Raman spectra of samples when using a 785 nm micro-Raman system because the green fluorescence wavelength of GFP is well below the Stokes-Raman shifted spectral region.

  2. Serodiagnosis of La Crosse virus infections in humans by detection of immunoglobulin M class antibodies.

    PubMed Central

    Calisher, C H; Pretzman, C I; Muth, D J; Parsons, M A; Peterson, E D

    1986-01-01

    Sera from 92 humans with illnesses clinically compatible with those caused by California serogroup virus infections were tested for antibody to La Crosse (LAC) virus by using the immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC ELISA), the IgG ELISA, and the hemagglutination inhibition (HI), complement fixation and serum dilution-plaque reduction neutralization tests. On the reported day of onset of illness in 18 individuals, 94% had IgM antibody, 50% had neutralization antibody, 33% had HI antibody, and 11% had IgG antibody. Neutralization, HI, and IgG antibody prevalence rates increased thereafter, whereas IgM antibody prevalence remained high (92% 2 or more weeks after the onset of illness). It was concluded that the MAC ELISA is a sensitive test for the presence of antibody to LAC virus. The sensitivity of the MAC ELISA and the rapidity with which it can be performed appear to provide a powerful tool for the clinically relevant serodiagnosis of LAC virus infections in humans. PMID:3700625

  3. Variability in pathobiology of South Korean H5N1 high-pathogenicity avian influenza virus infection for 5 species of migratory waterfowl

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The biological outcome of H5N1 high pathogenicity avian influenza (HPAI) virus infection in wild waterfowl is poorly understood. This study examined infectivity and pathobiology of A/chicken/Korea/IS/06 (H5N1) HPAI virus infection in Mute swans (Cygnus olor), Greylag geese (Anser anser), Ruddy Sheld...

  4. Abortively Infected Astrocytes Appear To Represent the Main Source of Interferon Beta in the Virus-Infected Brain

    PubMed Central

    Pfefferkorn, Cathleen; Kallfass, Carsten; Lienenklaus, Stefan; Spanier, Julia; Kalinke, Ulrich; Rieder, Martina; Conzelmann, Karl-Klaus; Michiels, Thomas

    2015-01-01

    ABSTRACT Interferon beta (IFN-β) is a key component of cellular innate immunity in mammals, and it constitutes the first line of defense during viral infection. Studies with cultured cells previously showed that almost all nucleated cells are able to produce IFN-β to various extents, but information about the in vivo sources of IFN-β remains incomplete. By applying immunohistochemistry and employing conditional-reporter mice that express firefly luciferase under the control of the IFN-β promoter in either all or only distinct cell types, we found that astrocytes are the main producers of IFN-β after infection of the brain with diverse neurotropic viruses, including rabies virus, Theiler's murine encephalomyelitis virus, and vesicular stomatitis virus. Analysis of a panel of knockout mouse strains revealed that sensing of viral components via both RIG-I-like helicases and Toll-like receptors contributes to IFN induction in the infected brain. A genetic approach to permanently mark rabies virus-infected cells in the brain showed that a substantial number of astrocytes became labeled and, therefore, must have been infected by the virus at least transiently. Thus, our results strongly indicate that abortive viral infection of astrocytes can trigger pattern recognition receptor signaling events which result in secretion of IFN-β that confers antiviral protection. IMPORTANCE Previous work indicated that astrocytes are the main producers of IFN after viral infection of the central nervous system (CNS), but it remained unclear how astrocytes might sense those viruses which preferentially replicate in neurons. We have now shown that virus sensing by both RIG-I-like helicases and Toll-like receptors is involved. Our results further demonstrate that astrocytes get infected in a nonproductive manner under these conditions, indicating that abortive infection of astrocytes plays a previously unappreciated role in the innate antiviral defenses of the CNS. PMID:26656686

  5. Flying-Fox Species Density - A Spatial Risk Factor for Hendra Virus Infection in Horses in Eastern Australia

    PubMed Central

    Smith, Craig; Skelly, Chris; Kung, Nina; Roberts, Billie; Field, Hume

    2014-01-01

    Hendra virus causes sporadic but typically fatal infection in horses and humans in eastern Australia. Fruit-bats of the genus Pteropus (commonly known as flying-foxes) are the natural host of the virus, and the putative source of infection in horses; infected horses are the source of human infection. Effective treatment is lacking in both horses and humans, and notwithstanding the recent availability of a vaccine for horses, exposure risk mitigation remains an important infection control strategy. This study sought to inform risk mitigation by identifying spatial and environmental risk factors for equine infection using multiple analytical approaches to investigate the relationship between plausible variables and reported Hendra virus infection in horses. Spatial autocorrelation (Global Moran’s I) showed significant clustering of equine cases at a distance of 40 km, a distance consistent with the foraging ‘footprint’ of a flying-fox roost, suggesting the latter as a biologically plausible basis for the clustering. Getis-Ord Gi* analysis identified multiple equine infection hot spots along the eastern Australia coast from far north Queensland to central New South Wales, with the largest extending for nearly 300 km from southern Queensland to northern New South Wales. Geographically weighted regression (GWR) showed the density of P. alecto and P. conspicillatus to have the strongest positive correlation with equine case locations, suggesting these species are more likely a source of infection of Hendra virus for horses than P. poliocephalus or P. scapulatus. The density of horses, climate variables and vegetation variables were not found to be a significant risk factors, but the residuals from the GWR suggest that additional unidentified risk factors exist at the property level. Further investigations and comparisons between case and control properties are needed to identify these local risk factors. PMID:24936789

  6. Flying-fox species density--a spatial risk factor for Hendra virus infection in horses in eastern Australia.

    PubMed

    Smith, Craig; Skelly, Chris; Kung, Nina; Roberts, Billie; Field, Hume

    2014-01-01

    Hendra virus causes sporadic but typically fatal infection in horses and humans in eastern Australia. Fruit-bats of the genus Pteropus (commonly known as flying-foxes) are the natural host of the virus, and the putative source of infection in horses; infected horses are the source of human infection. Effective treatment is lacking in both horses and humans, and notwithstanding the recent availability of a vaccine for horses, exposure risk mitigation remains an important infection control strategy. This study sought to inform risk mitigation by identifying spatial and environmental risk factors for equine infection using multiple analytical approaches to investigate the relationship between plausible variables and reported Hendra virus infection in horses. Spatial autocorrelation (Global Moran's I) showed significant clustering of equine cases at a distance of 40 km, a distance consistent with the foraging 'footprint' of a flying-fox roost, suggesting the latter as a biologically plausible basis for the clustering. Getis-Ord Gi* analysis identified multiple equine infection hot spots along the eastern Australia coast from far north Queensland to central New South Wales, with the largest extending for nearly 300 km from southern Queensland to northern New South Wales. Geographically weighted regression (GWR) showed the density of P. alecto and P. conspicillatus to have the strongest positive correlation with equine case locations, suggesting these species are more likely a source of infection of Hendra virus for horses than P. poliocephalus or P. scapulatus. The density of horses, climate variables and vegetation variables were not found to be a significant risk factors, but the residuals from the GWR suggest that additional unidentified risk factors exist at the property level. Further investigations and comparisons between case and control properties are needed to identify these local risk factors. PMID:24936789

  7. Thoracic computerized tomographic (CT) findings in 2009 influenza A (H1N1) virus infection in Isfahan, Iran

    PubMed Central

    Rostami, Mojtaba; Javadi, Abbas-Ali; Khorvash, Farzin; Mostafavizadeh, Kamyar; Adibi, Atoosa; Babak, Anahita; Ataei, Behrooz; Meidani, Mohsen; Naeini, Alireza Emami; Salehi, Hasan; Avijgan, Majid; Yazdani, Mohammad Reza; Rezaei, Farshid

    2011-01-01

    BACKGROUND: Pandemic 2009 H1N1 influenza A virus arrived at Isfahan in August 2009. The virus is still circulating in the world. The abnormal thoracic computerized tomographic (CT) scan findings vary widely among the studies of 2009 H1N1 influenza. We evaluated the thoracic CT findings in patients with 2009 H1N1 virus infection to describe findings compared to previously reported findings, and to suggest patterns that may be suggestive for 2009 influenza A (H1N1) in an appropriate clinical setting. METHODS: Retrospectively, the archive of all patients with a diagnosis of 2009 H1N1 influenza A were reviewed, in Al-Zahra Hospital in Isfahan, central Iran, between September 23rd 2009 to February 20th 2010. Out of 216 patients with confirmed 2009 influenza A (H1N1) virus, 26 cases with abnormal CT were enrolled in the study. Radiologic findings were characterized by the type and pattern of opacities and zonal distribution. RESULTS: Patchy infiltration (34.6%), lobar consolidation (30.8%), and interstitial infiltration (26.9%) with airbronchogram (38.5%) were the predominant findings in our patients. Bilateral distribution was seen in 80.8% of the patients. Only one patient (3.8%) showed ground-glass opacity, predominant radiographic finding in the previous reports and severe acute respiratory syndrome (SARS). CONCLUSIONS: The most common thoracic CT findings in pandemic H1N1 were patchy infiltration, lobar consolidation, and interstitial infiltration with airbronchogram and bilateral distribution. While these findings can be associated with other infections; they may be suggestive to 2009 influenza A (H1N1) in the appropriate clinical setting. Various radiographic patterns can be seen in thoracic CT scans of the influenza patients. Imaging findings are nonspecific. PMID:22091280

  8. Hearing Loss in Infants with Microcephaly and Evidence of Congenital Zika Virus Infection - Brazil, November 2015-May 2016.

    PubMed

    Leal, Mariana C; Muniz, Lilian F; Ferreira, Tamires S A; Santos, Cristiane M; Almeida, Luciana C; Van Der Linden, Vanessa; Ramos, Regina C F; Rodrigues, Laura C; Neto, Silvio S Caldas

    2016-01-01

    Congenital infection with Zika virus causes microcephaly and other brain abnormalities (1). Hearing loss associated with other congenital viral infections is well described; however, little is known about hearing loss in infants with congenital Zika virus infection. A retrospective assessment of a series of 70 infants aged 0-10 months with microcephaly and laboratory evidence of Zika virus infection was conducted by the Hospital Agamenon Magalhães in Brazil and partners. The infants were enrolled during November 2015-May 2016 and had screening and diagnostic hearing tests. Five (7%) infants had sensorineural hearing loss, all of whom had severe microcephaly; however, one child was tested after receiving treatment with an ototoxic antibiotic. If this child is excluded, the prevalence of sensorineural hearing loss was 5.8% (four of 69), which is similar to that seen in association with other congenital viral infections. Additional information is needed to understand the prevalence and spectrum of hearing loss in children with congenital Zika virus infection; all infants born to women with evidence of Zika virus infection during pregnancy should have their hearing tested, including infants who appear normal at birth. PMID:27585248

  9. Chronic ethanol exposure selectively inhibits the influenza-specific CD8 T cell response during influenza A virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is well established that chronic ethanol (EtOH) consumption is associated with increases in the incidence and disease severity of respiratory infections. Our recent work as demonstrated that this increase in disease severity to influenza virus infections is due, in part, to a failure to mount a r...

  10. Simultaneous outbreaks of dengue, chikungunya and Zika virus infections: diagnosis challenge in a returning traveller with nonspecific febrile illness

    PubMed Central

    Moulin, E.; Selby, K.; Cherpillod, P.; Kaiser, L.; Boillat-Blanco, N.

    2016-01-01

    Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes-borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm. PMID:27006779

  11. IgA antibody response of swine to foot-and-mouth disease virus infection and vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-Mouth Disease Virus (FMDV) specific antibodies, specifically neutralizing antibodies, are known to protect against virus infection in vitro and are predictive of protection in vivo. Of interest is the role of antibodies against FMDV in mucosal secretions, in particular in the oropharyngeal ...

  12. Simultaneous outbreaks of dengue, chikungunya and Zika virus infections: diagnosis challenge in a returning traveller with nonspecific febrile illness.

    PubMed

    Moulin, E; Selby, K; Cherpillod, P; Kaiser, L; Boillat-Blanco, N

    2016-05-01

    Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes-borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm. PMID:27006779

  13. Contact tracing for influenza A(H1N1)pdm09 virus-infected passenger on international flight.

    PubMed

    Shankar, Ananda G; Janmohamed, Kulsum; Olowokure, Babatunde; Smith, Gillian E; Hogan, Angela H; De Souza, Valerie; Wallensten, Anders; Oliver, Isabel; Blatchford, Oliver; Cleary, Paul; Ibbotson, Sue

    2014-01-01

    In April 2009, influenza A(H1N1)pdm09 virus infection was confirmed in a person who had been symptomatic while traveling on a commercial flight from Mexico to the United Kingdom. Retrospective public health investigation and contact tracing led to the identification of 8 additional confirmed cases among passengers and community contacts of passengers. PMID:24377724

  14. A white spot syndrome virus microRNA promotes the virus infection by targeting the host STAT

    PubMed Central

    Ren, Qian; Huang, Ying; He, Yaodong; Wang, Wen; Zhang, Xiaobo

    2015-01-01

    JAK/STAT pathway plays an important role in invertebrates during virus infection. However the microRNA (miRNA)-mediated regulation of JAK/STAT is not intensively investigated. Viral miRNAs, encoded by virus genome, have emerged as important regulators in the virus-host interactions. In this study, a WSSV (white spot syndrome virus)-encoded miRNA (WSSV-miR-22) was characterized in shrimp during virus infection. The results showed that the viral miRNA could promote WSSV infection in shrimp by targeting the host STAT gene. When the expression of JAK or STAT was knocked down by sequence-specific siRNA, the WSSV copies in shrimp were significantly increased, indicating that the JAK/STAT played positive roles in the antiviral immunity of shrimp. The further findings revealed that TEP1 and TEP2 were the effectors of JAK-STAT signaling pathway. The silencing of TEP1 or TEP2 led to an increase of WSSV copies in shrimp, showing TEP1 and TEP2 were involved in the shrimp immune response against virus infection. Therefore our study presented a novel viral miRNA-mediated JAK/STAT-TEP1/TEP2 signaling pathway in virus infection. PMID:26671453

  15. A white spot syndrome virus microRNA promotes the virus infection by targeting the host STAT.

    PubMed

    Ren, Qian; Huang, Ying; He, Yaodong; Wang, Wen; Zhang, Xiaobo

    2015-01-01

    JAK/STAT pathway plays an important role in invertebrates during virus infection. However the microRNA (miRNA)-mediated regulation of JAK/STAT is not intensively investigated. Viral miRNAs, encoded by virus genome, have emerged as important regulators in the virus-host interactions. In this study, a WSSV (white spot syndrome virus)-encoded miRNA (WSSV-miR-22) was characterized in shrimp during virus infection. The results showed that the viral miRNA could promote WSSV infection in shrimp by targeting the host STAT gene. When the expression of JAK or STAT was knocked down by sequence-specific siRNA, the WSSV copies in shrimp were significantly increased, indicating that the JAK/STAT played positive roles in the antiviral immunity of shrimp. The further findings revealed that TEP1 and TEP2 were the effectors of JAK-STAT signaling pathway. The silencing of TEP1 or TEP2 led to an increase of WSSV copies in shrimp, showing TEP1 and TEP2 were involved in the shrimp immune response against virus infection. Therefore our study presented a novel viral miRNA-mediated JAK/STAT-TEP1/TEP2 signaling pathway in virus infection. PMID:26671453

  16. 78 FR 63218 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Chronic Hepatitis C Virus... availability of a draft guidance for industry entitled ``Chronic Hepatitis C Virus Infection: Developing Direct... of development of direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C....

  17. 75 FR 55797 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Chronic Hepatitis C Virus... availability of a draft guidance for industry entitled ``Chronic Hepatitis C Virus Infection: Developing Direct... specific steps in the hepatitis C virus (HCV) replication cycle. The guidance outlines the types...

  18. 78 FR 67175 - Proposed Collection; 60-Day Comment Request: Incident HIV/Hepatitis B Virus Infections in South...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    .../ Hepatitis B Virus Infections in South African Blood Donors: Behavioral Risk Factors, Genotypes and... collection projects, the National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health.../Hepatitis B virus (HBV) infections in South African blood donors: Behavioral risk factors, genotypes...

  19. Mycoplasma hominis-Associated Parapharyngeal Abscess following Acute Epstein-Barr Virus Infection in a Previously Immunocompetent Adult ▿

    PubMed Central

    Kennedy, Karina J.; Prince, Sam; Makeham, Timothy

    2009-01-01

    Mycoplasma hominis most frequently causes diseases of the genitourinary tract. Extragenital infections are uncommon, with almost all occurring in immunosuppressed persons or those predisposed due to trauma or surgery. We present the case of a previously well man who developed an M. hominis-associated parapharyngeal abscess following acute Epstein-Barr virus infection. PMID:19641070

  20. Mycoplasma hominis-associated parapharyngeal abscess following acute Epstein-Barr virus infection in a previously immunocompetent adult.

    PubMed

    Kennedy, Karina J; Prince, Sam; Makeham, Timothy

    2009-09-01

    Mycoplasma hominis most frequently causes diseases of the genitourinary tract. Extragenital infections are uncommon, with almost all occurring in immunosuppressed persons or those predisposed due to trauma or surgery. We present the case of a previously well man who developed an M. hominis-associated parapharyngeal abscess following acute Epstein-Barr virus infection. PMID:19641070

  1. Analysis of the interactions between host factor Sam68 and viral elements during foot-and-mouth disease virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The nuclear protein Src-associated protein of 68 kDa in mitosis (Sam68) is known to bind RNA and be involved in cellular processes triggered in response to environmental stresses, including virus infection. Interestingly, Sam68, is a multi-functional protein implicated in the life cycle of retroviru...

  2. Hemorrhagic Fever Occurs After Intravenous, But Not After Intragastric, Inoculation of Rhesus Macaques With Lymphocytic Choriomeningitis Virus

    PubMed Central

    Lukashevich, Igor S.; Djavani, Mahmoud; Rodas, Juan D.; Zapata, Juan C.; Usborne, Amy; Emerson, Carol; Mitchen, Jacque; Jahrling, Peter B.; Salvato, Maria S.

    2008-01-01

    Arenaviruses can cause hemorrhagic fever and death in primates and guinea pigs, but these viruses are not highly pathogenic for most rodent carriers. In the United States, arenaviruses precipitated outbreaks of hepatitis in captive monkeys, and they present an emerging health threat in the tropical areas of Africa and South America. We describe infection of rhesus macaques with the prototype arenavirus, lymphocytic choriome-ningitis virus (LCMV), using the WE strain that has been known to cause both encephalopathy and multifocal hemorrhage. Five macaques were inoculated: two by the intravenous (i.v.) and three by the intragastric (i.g.) route. Whereas the two i.v.-inoculated monkeys developed signs and lesions consistent with fatal hemorrhagic fever, the i.g.-inoculated monkeys had an attenuated infection with no disease. Pathological signs of the primate i.v. infection differ significantly from guinea pig arenavirus infections and make this a superior model for human viral hemorrhagic disease. PMID:11992578

  3. A genome-wide RNAi screening method to discover novel genes involved in virus infection.

    PubMed

    Panda, Debasis; Cherry, Sara

    2015-12-01

    Systematic and comprehensive analysis of host cell proteins involved in virus infection has been difficult in large part due to the lack of robust unbiased methods for their identification. Recent technological breakthroughs allowing development of cell-based genetic screens have greatly facilitated our understanding of virus-host interactions. These include instrumentation for processing in microtiter plates (e.g., 384 well), coupled with sensitive readers and off-the-shelf analysis and informatics pipelines. Because viruses are a significant threat to human health, a better understanding of the cellular factors that impact infection would pave the way for the development of new therapeutics. Here we describe the development and implementation of a genome-wide siRNA screen against a virus using human cells. PMID:26164699

  4. Endogenous Murine BST-2/Tetherin Is Not a Major Restriction Factor of Influenza A Virus Infection

    PubMed Central

    Job, Emma R.; Moffat, Jessica M.; Wakim, Linda M.; Gonelli, Christopher A.; Purcell, Damien F. J.; Brooks, Andrew G.; Villadangos, Jose A.; Reading, Patrick C.; Mintern, Justine D.

    2015-01-01

    BST-2 (tetherin, CD317, HM1.24) restricts virus growth by tethering enveloped viruses to the cell surface. The role of BST-2 during influenza A virus infection (IAV) is controversial. Here, we assessed the capacity of endogenous BST-2 to restrict IAV in primary murine cells. IAV infection increased BST-2 surface expression by primary macrophages, but not alveolar epithelial cells (AEC). BST-2-deficient AEC and macrophages displayed no difference in susceptibility to IAV infection relative to wild type cells. Furthermore, BST-2 played little role in infectious IAV release from either AEC or macrophages. To examine BST-2 during IAV infection in vivo, we infected BST-2-deficient mice. No difference in weight loss or in viral loads in the lungs and/or nasal tissues were detected between BST-2-deficient and wild type animals. This study rules out a major role for endogenous BST-2 in modulating IAV in the mouse model of infection. PMID:26566124

  5. Ionizing air affects influenza virus infectivity and prevents airborne-transmission.

    PubMed

    Hagbom, Marie; Nordgren, Johan; Nybom, Rolf; Hedlund, Kjell-Olof; Wigzell, Hans; Svensson, Lennart

    2015-01-01

    By the use of a modified ionizer device we describe effective prevention of airborne transmitted influenza A (strain Panama 99) virus infection between animals and inactivation of virus (>97%). Active ionizer prevented 100% (4/4) of guinea pigs from infection. Moreover, the device effectively captured airborne transmitted calicivirus, rotavirus and influenza virus, with recovery rates up to 21% after 40 min in a 19 m(3) room. The ionizer generates negative ions, rendering airborne particles/aerosol droplets negatively charged and electrostatically attracts them to a positively charged collector plate. Trapped viruses are then identified by reverse transcription quantitative real-time PCR. The device enables unique possibilities for rapid and simple removal of virus from air and offers possibilities to simultaneously identify and prevent airborne transmission of viruses. PMID:26101102

  6. Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro.

    PubMed

    Denisova, Oxana V; Söderholm, Sandra; Virtanen, Salla; Von Schantz, Carina; Bychkov, Dmitrii; Vashchinkina, Elena; Desloovere, Jens; Tynell, Janne; Ikonen, Niina; Theisen, Linda L; Nyman, Tuula A; Matikainen, Sampsa; Kallioniemi, Olli; Julkunen, Ilkka; Muller, Claude P; Saelens, Xavier; Verkhusha, Vladislav V; Kainov, Denis E

    2014-07-01

    The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infection in vitro. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus. PMID:24752266

  7. [Two types of NP-NP associations in influenza virus-infected cells].

    PubMed

    Semenova, N P; Chumakov, V M; Grigor'eva, T A; Rudneva, I A; Burov, V V; Prokudina, E N

    2007-01-01

    Two types of NP-NP associations are shown to form in the influenza virus-infected cells. Early NP synthesis gives rise to NP associations stabilized by relatively weak bonds. These structures are designed as NP multimers. The high protease- and heat-sensitivities allow NP-multimers to be regarded as incompletely folded proteins. Post-translationally, NP-multimers transform to compact NP associations (NP oligomers) that are relatively highly heat-and protease-resistant. The NP-multimers untransformed to the folded compact NP-oligomers accumulate in the cells and partially degraded. Whether both types of NP-NP associations may be of significance is under discussion. PMID:17601043

  8. [Gastric uptake of gallium67 in the human immunodeficiency virus infection].

    PubMed

    Escalera Temprado, T; Banzo Marraco, J; Abós Olivares, M D; Olave Rubio, M T; Prats Rivera, E; García López, F; Razola Alba, P

    2004-02-01

    Nowadays, the human immunodeficiency virus infection (HIV) is a chronic disease. In the frequent clinical situations with fever, lymph nodes and loss weight it is necessary to determine their etiology, for establishing a specific treatment. Gastrointestinal opportunistic infections or gastric lymphomatous or sarcomatous process, which can accumulate Ga67, may be present in the patient with acquired immunodeficiency syndrome. We report 2 cases with gastric uptake in which endoscopy and biopsy was obtained. In the first one, with previous treatment with omeprazol and almalgate for gastroesophagic reflux, endoscopy and biopsy were normal and in the second patient an Helicobacter pylori infection was diagnosed. We think that gastric uptake of Ga67 in HIV patients, must indicate to the clinician to rule out associated pathologies. PMID:14974895

  9. Rhizosphere mycoflora of healthy and yellow vein mosaic virus infected okra (Abelmoschus esculentus) plants.

    PubMed

    Singh, S J; Tewari, R P

    1979-01-01

    Investigations on the rhizosphere mycoflora of healthy and virus (YVMV) infected okra plants showed a higher fungal population in the rhizosphere of healthy plants at preflowering and post-flowering stages than in that of diseased ones. Maximum population was observed during flowering both in healthy and diseased plant rhizosphere as well as in non-rhizosphere soil. However, virus infected plants showed a higher population at the flowering stage than healthy ones. The quantitative differences in the rhizosphere of healthy and diseased plants during flowering seem to be due to a change in C/N ratio and amino acids. The drastic reduction in diseased plant rhizospheres during the post-flowering stage may be due to either change in C/N ratio unfavourable to mycoflora or production of some toxic substances inhibiting multiplication of the mycoflora. PMID:94749

  10. Akt Inhibitor MK2206 Prevents Influenza pH1N1 Virus Infection In Vitro

    PubMed Central

    Denisova, Oxana V.; Söderholm, Sandra; Virtanen, Salla; Von Schantz, Carina; Bychkov, Dmitrii; Vashchinkina, Elena; Desloovere, Jens; Tynell, Janne; Ikonen, Niina; Theisen, Linda L.; Nyman, Tuula A.; Matikainen, Sampsa; Kallioniemi, Olli; Julkunen, Ilkka; Muller, Claude P.; Saelens, Xavier; Verkhusha, Vladislav V.

    2014-01-01

    The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infection in vitro. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus. PMID:24752266

  11. Course of pandemic influenza A(H1N1) 2009 virus infection in Dutch patients

    PubMed Central

    Friesema, Ingrid H. M.; Meijer, Adam; van Gageldonk‐Lafeber, Arianne B.; van der Lubben, Mariken; van Beek, Janko; Donker, Gé A.; Prins, Jan M.; de Jong, Menno D.; Boskamp, Simone; Isken, Leslie D.; Koopmans, Marion P. G.; van der Sande, Marianne A. B.

    2012-01-01

    Please cite this paper as: Friesema et al. (2012). Course of pandemic influenza A(H1N1) 2009 virus infection in Dutch patients. Influenza and Other Respiratory Viruses 6(3), e16–e20. The clinical dynamics of influenza A(H1N1) 2009 infections in 61 laboratory‐confirmed Dutch cases were examined. An episode lasted a median of 7·5 days of which 2 days included fever. Respiratory symptoms resolved slowly, while systemic symptoms peaked early in the episode and disappeared quickly. Severity of each symptom was rated highest in the first few days. Furthermore, diarrhoea was negatively associated with viral load, but not with faecal excretion of influenza virus. Cases with comorbidities appeared to have higher viral loads than the cases without, suggesting a less effective immune response. These results complement information obtained through traditional surveillance. PMID:22372759

  12. Rabies virus infection of primary neuronal cultures and adult mice: failure to demonstrate evidence of excitotoxicity.

    PubMed

    Weli, Simon C; Scott, Courtney A; Ward, Christopher A; Jackson, Alan C

    2006-10-01

    Cultures derived from the cerebral cortices and hippocampi of 17-day-old mouse fetuses infected with the CVS strain of rabies virus showed loss of trypan blue exclusion, morphological apoptotic features, and activated caspase 3 expression, indicating apoptosis. The NMDA (N-methyl-D-aspartate acid) antagonists ketamine (125 microM) and MK-801 (60 microM) were found to have no significant neuroprotective effect on CVS-infected neurons, while the caspase inhibitor Ac-Asp-Glu-Val aspartic acid aldehyde (25 microM) exerted a marked neuroprotective effect. Glutamate-stimulated increases in levels of intracellular calcium were reduced in CVS-infected hippocampal neurons. Ketamine (120 mg/kg of body weight/day intraperitoneally) given to CVS-infected adult mice produced no beneficial effects. We have found no supportive evidence that excitotoxicity plays an important role in rabies virus infection. PMID:17005706

  13. [Hydrops of the gallbladder associated with Epstein-Barr virus infection].

    PubMed

    Gómez de la Torre, R; Claros González, I J; Rubio Barbón, S; Triviño López, A

    2000-01-01

    A 50-year-old male developed Hydrops of Gallbladder during the course of Epstein-Barr virus infection. The patient had a history of acute encephalitis one month prior to admission. Physical examination revealed jaundice and hepatomegaly. Liver function tests were abnormal and the white blood count was normal with 15% of atypical lymphocytes. Ultrasonography revealed a distended gall-bladder without wall thickening or cholelithiasis. The diagnoses of primary Epstein-Barr infection was made by positivity from EBV VCA IgM serological study. Two weeks later, total clinical, biochemical and ultrasonography resolution were observed. We comment this exceptionally presentation of EBV infection. The great variability of clinical pictures of Infectious Mononucleosis was emphasized. PMID:10730404

  14. Frequency and significance of feline leukemia virus infection in necropsied cats.

    PubMed

    Reinacher, M; Theilen, G

    1987-06-01

    Feline leukemia virus (FeLV) infection was diagnosed immunohistologically on paraffin-embedded tissues obtained from 1,095 necropsied cats. Significant association of FeLV infection was demonstrated by chi 2 and Fisher's tests with various conditions and diseases (ie, anemia, tumors of the leukemia/lymphoma complex, feline infectious peritonitis, bacterial infections, emaciation, FeLV-associated enteritis, lymphatic hyperplasia, and hemorrhage). Unexpected findings associated with FeLV infection were icterus, several types of hepatitis, and liver degeneration. A negative association with FeLV infection was found for most parasitic and viral infections, including feline panleukopenia. Neither positive nor negative associations were established for FeLV infection and most forms of nephritis, including severe glomerulonephritis. Feline leukemia virus-infected cats were significantly (Kruskal-Wallis test) older than were FeLV-negative cats with the same nonneoplastic FeLV-associated diseases. PMID:3037951

  15. Hepatitis C virus infection in Iceland: a recently introduced blood-borne disease.

    PubMed Central

    Löve, A.; Stanzeit, B.

    1994-01-01

    This study demonstrates a very high prevalence of antibodies to hepatitis C virus among Icelandic intravenous (i.v.) drug users. Of 152 identified i.v. drug users 95 (63%) were shown to have antibodies to the hepatitis C virus. In contrast the seroprevalence in the general Icelandic population is low, (0.2%). Almost all cases of hepatitis C virus infection in Iceland are due to i.v. drug use or to use of infected blood or blood products. Sporadic cases with unexplained modes of transmission, a significant portion of hepatitis C infections elsewhere, are virtually non-existent in Iceland. The results of this study are consistent with the hypothesis that the sporadic community-acquired cases could be caused by blood transfer due to bites from insect vectors such as mosquitoes which are not found in Iceland. PMID:7527781

  16. Antiviral effects of human fibroblast interferon from Escherichia coli against encephalomyocarditis virus infection of squirrel monkeys.

    PubMed

    Weck, P K; Harkins, R N; Stebbing, N

    1983-02-01

    Recombinant DNA methodology has allowed the production of human fibroblast interferon (IFN-beta) from Escherichia coli and this material, in highly purified form, has been shown to reduce viraemia and mortality in encephalomyocarditis (EMC) virus-infected squirrel monkeys. These effects are dose related: six treatments over 4 days at 10(6) U/kg and 3 x 10(3) U/kg have comparable efficacy, whereas treatments at 10(3) U/kg are ineffective. The recombinant DNA-derived IFN-beta appears to be as effective as natural fibroblast cell-derived IFN-beta and both materials are effective by the intramuscular or intravenous routes. Thus, even though previous studies have shown that low circulating concentrations of IFN-beta are observed after intramuscular injections, the present data indicate that this slow release from the muscle can still confer protection. PMID:6300291

  17. Nipah virus infection outbreak with nosocomial and corpse-to-human transmission, Bangladesh.

    PubMed

    Sazzad, Hossain M S; Hossain, M Jahangir; Gurley, Emily S; Ameen, Kazi M H; Parveen, Shahana; Islam, M Saiful; Faruque, Labib I; Podder, Goutam; Banu, Sultana S; Lo, Michael K; Rollin, Pierre E; Rota, Paul A; Daszak, Peter; Rahman, Mahmudur; Luby, Stephen P

    2013-02-01

    Active Nipah virus encephalitis surveillance identified an encephalitis cluster and sporadic cases in Faridpur, Bangladesh, in January 2010. We identified 16 case-patients; 14 of these patients died. For 1 case-patient, the only known exposure was hugging a deceased patient with a probable case, while another case-patient's exposure involved preparing the same corpse for burial by removing oral secretions and anogenital excreta with a cloth and bare hands. Among 7 persons with confirmed sporadic cases, 6 died, including a physician who had physically examined encephalitis patients without gloves or a mask. Nipah virus-infected patients were more likely than community-based controls to report drinking raw date palm sap and to have had physical contact with an encephalitis patient (29% vs. 4%, matched odds ratio undefined). Efforts to prevent transmission should focus on reducing caregivers' exposure to infected patients' bodily secretions during care and traditional burial practices. PMID:23347678

  18. How does the stressed out ER find relief during virus infection?

    PubMed

    Verchot, Jeanmarie

    2016-04-01

    The endoplasmic reticulum and Golgi network (ERGN) is vital to most cellular biosynthetic processes. Many positive strand RNA viruses depend upon the ERGN for replication, maturation, and egress. Viruses induce changes in ER architecture and stimulate fatty acid synthesis to create environments that can scaffold replication complexes, plant virus movement complexes, or virion maturation. Potato virus X (PVX) and Turnip mosaic virus (TuMV) each encode small membrane binding proteins that embed in the ERGN and activate the unfolded protein response (UPR). The UPR ensures ERGN homeostasis in the face of environmental assaults that could negatively impact the biosynthetic functions of the ERGN. This article explores the relationship between ER stress, the UPR, and membrane synthesis occurring during virus infection. PMID:26871502

  19. Endogenous changes in citokinin activity in systemically virus-infected plants.

    PubMed

    Pennazio, S; Roggero, P

    1998-10-01

    Viral diseases may alter cytokinin activity in plants, an effect associated with morphological and physiological changes. Experimental evidence indicates that the level of cytokinins may be both reduced or increased depending on different viral diseases. Circumstantial evidence suggests a change in virus-diseased plants showing specific alterations such as tumors and disorders in carbon partitioning and chlorophyll metabolism. The knowledge reached on cytokinin changes is not yet adequate to the importance of their role during viral pathogenesis. Furthermore, unclear results are available on the effect of cytokinins on virus replication. There is little information on how systemic virus infection alters cytokinin metabolism and no information on how this alteration can affect plant metabolism. Nevertheless, a possible control of some viral diseases by biomanipulation of plants to modify the endogenous levels of such hormone may be suggested, provided that higher levels of cytokinins do not increase the rate of virus replication. PMID:9812325

  20. Serological survey of hepatitis E virus infection in farmed and pet rabbits in Italy.

    PubMed

    Di Bartolo, Ilaria; De Sabato, L; Marata, A; Martinelli, N; Magistrali, C F; Monini, M; Ponterio, E; Ostanello, F; Ruggeri, F M

    2016-05-01

    The recent identification in rabbits of hepatitis E viruses (HEV) related to viruses infecting humans raises the question of the role of this species as possible HEV reservoir. A serological survey on rabbit HEV infection was conducted in Italy during 2013-2014, including both farmed and pet rabbits. We found an anti-HEV antibody seroprevalence of 3.40 % in 206 farmed rabbits (collected on 7 farms) and 6.56 % in 122 pets. RNA was extracted from IgG-positive sera and analyzed by HEV-specific real-time RT-PCR. None of the samples were positive, confirming that no viremia was present in the presence of IgG. Only one serum sample from a farmed rabbit was positive for IgM, but no HEV RNA was detected in it. Pet rabbit feces were also tested for HEV RNA, with negative results. This finding suggests that HEV is circulating in rabbits in Italy. PMID:26873813

  1. A systems approach to understanding human rhinovirus and influenza virus infection.

    PubMed

    Kim, Taek-Kyun; Bheda-Malge, Anjali; Lin, Yakang; Sreekrishna, Koti; Adams, Rachel; Robinson, Michael K; Bascom, Charles C; Tiesman, Jay P; Isfort, Robert J; Gelinas, Richard

    2015-12-01

    Human rhinovirus and influenza virus infections of the upper airway lead to colds and the flu and can trigger exacerbations of lower airway diseases including asthma and chronic obstructive pulmonary disease. Novel diagnostic and therapeutic targets are still needed to differentiate between the cold and the flu, since the clinical course of influenza can be severe while that of rhinovirus is usually more mild. In our investigation of influenza and rhinovirus infection of human respiratory epithelial cells, we used a systems approach to identify the temporally changing patterns of host gene expression from these viruses. After infection of human bronchial epithelial cells (BEAS-2B) with rhinovirus, influenza virus or co-infection with both viruses, we studied the time-course of host gene expression changes over three days. We modeled host responses to these viral infections with time and documented the qualitative and quantitative differences in innate immune activation and regulation. PMID:26437235

  2. Surveillance for persistent bovine viral diarrhea virus infection in four artificial insemination centers.

    PubMed

    Howard, T H; Bean, B; Hillman, R; Monke, D R

    1990-06-15

    Four large bovine artificial insemination centers implemented a program of surveillance of resident and newly acquired bulls for persistent bovine viral diarrhea virus infection. Infection was identified in 12 of 1,538 bulls. Several clinical abnormalities, including acute and chronic mucosal disease, were evident among the persistently infected bulls. Semen produced by such bulls consistently contained bovine viral diarrhea virus, and such contamination was not always accompanied by diminished seminal quality. Infected bulls were detected by means of virus isolation tests performed on blood specimens, but not by use of serologic testing. Ten of the 12 persistently infected bulls were results of embryo transfer. Virologic surveillance of breeding herds, artificial insemination and embryo transfer centers, and the cattle trade is necessary to prevent spread of this virus by modern cattle breeding practices. Attention is also necessary to prevent contamination by this virus of the fluids used for recovery, in vitro manipulation, and transfer of bovine embryos. PMID:2163996

  3. The role of T-cell-mediated mechanisms in virus infections of the nervous system.

    PubMed

    Dörries, R

    2001-01-01

    T lymphocytes play a decisive role in the course and clinical outcome of viral CNS infection. Summarizing the information presented in this review, the following sequence of events might occur during acute virus infection: After invasion of the host and a few initial rounds of replication, the virus reaches the CNS in most cases by hematogeneous spread. After passage through the BBB, CNS cells are infected and replication of virus in brain cells causes activation of the surrounding microglia population. Moreover, local production of IFN-alpha/beta induces expression of MHC antigens on CNS cells, and microglial cells start to phagocytose cellular debris, which accumulates as a result of virus-induced cytopathogenic effects. Upon phagocytosis, microglia becomes more activated; they up-regulate MHC molecules, acquire antigen presentation capabilities and secrete chemokines. This will initiate up-regulation of adhesion molecules on adjacent endothelial cells of the BBB. Transmigration of activated T lymphocytes through the BBB is followed by interaction with APC, presenting the appropriate peptides in the context of MHC antigens. It appears that CD8+ T lymphocytes are amongst the first mononuclear cells to arrive at the infected tissue. Without a doubt, their induction and attraction is deeply influenced by natural killer cells, which, after virus infection, secrete IFN-gamma, a cytokine that stimulates CD8+ T cells and diverts the immune response to a TH1-type CD4+ T cell-dominated response. Following the CD8+ T lymphocytes, tissue-penetrating, TH1 CD4+ T cells contact local APC. This results in a tremendous up-regulation of MHC molecules and secretion of more chemotactic and toxic substances. Consequently an increasing number of inflammatory cells, including macrophages/microglia and finally antibody-secreting plasma cells, are attracted to the site of virus infection. All trapped cells are mainly terminally differentiated cells that are going to enter apoptosis

  4. Adjoint equations and analysis of complex systems: Application to virus infection modelling

    NASA Astrophysics Data System (ADS)

    Marchuk, G. I.; Shutyaev, V.; Bocharov, G.

    2005-12-01

    Recent development of applied mathematics is characterized by ever increasing attempts to apply the modelling and computational approaches across various areas of the life sciences. The need for a rigorous analysis of the complex system dynamics in immunology has been recognized since more than three decades ago. The aim of the present paper is to draw attention to the method of adjoint equations. The methodology enables to obtain information about physical processes and examine the sensitivity of complex dynamical systems. This provides a basis for a better understanding of the causal relationships between the immune system's performance and its parameters and helps to improve the experimental design in the solution of applied problems. We show how the adjoint equations can be used to explain the changes in hepatitis B virus infection dynamics between individual patients.

  5. Ionizing air affects influenza virus infectivity and prevents airborne-transmission

    PubMed Central

    Hagbom, Marie; Nordgren, Johan; Nybom, Rolf; Hedlund, Kjell-Olof; Wigzell, Hans; Svensson, Lennart

    2015-01-01

    By the use of a modified ionizer device we describe effective prevention of airborne transmitted influenza A (strain Panama 99) virus infection between animals and inactivation of virus (>97%). Active ionizer prevented 100% (4/4) of guinea pigs from infection. Moreover, the device effectively captured airborne transmitted calicivirus, rotavirus and influenza virus, with recovery rates up to 21% after 40 min in a 19 m3 room. The ionizer generates negative ions, rendering airborne particles/aerosol droplets negatively charged and electrostatically attracts them to a positively charged collector plate. Trapped viruses are then identified by reverse transcription quantitative real-time PCR. The device enables unique possibilities for rapid and simple removal of virus from air and offers possibilities to simultaneously identify and prevent airborne transmission of viruses. PMID:26101102

  6. In ovo and in vitro susceptibility of American alligators (Alligator mississippiensis) to avian influenza virus infection.

    PubMed

    Temple, Bradley L; Finger, John W; Jones, Cheryl A; Gabbard, Jon D; Jelesijevic, Tomislav; Uhl, Elizabeth W; Hogan, Robert J; Glenn, Travis C; Tompkins, S Mark

    2015-01-01

    Avian influenza has emerged as one of the most ubiquitous viruses within our biosphere. Wild aquatic birds are believed to be the primary reservoir of all influenza viruses; however, the spillover of H5N1 highly pathogenic avian influenza (HPAI) and the recent swine-origin pandemic H1N1 viruses have sparked increased interest in identifying and understanding which and how many species can be infected. Moreover, novel influenza virus sequences were recently isolated from New World bats. Crocodilians have a slow rate of molecular evolution and are the sister group to birds; thus they are a logical reptilian group to explore susceptibility to influenza virus infection and they provide a link between birds and mammals. A primary American alligator (Alligator mississippiensis) cell line, and embryos, were infected with four, low pathogenic avian influenza (LPAI) strains to assess susceptibility to infection. Embryonated alligator eggs supported virus replication, as evidenced by the influenza virus M gene and infectious virus detected in allantoic fluid and by virus antigen staining in embryo tissues. Primary alligator cells were also inoculated with the LPAI viruses and showed susceptibility based upon antigen staining; however, the requirement for trypsin to support replication in cell culture limited replication. To assess influenza virus replication in culture, primary alligator cells were inoculated with H1N1 human influenza or H5N1 HPAI viruses that replicate independent of trypsin. Both viruses replicated efficiently in culture, even at the 30 C temperature preferred by the alligator cells. This research demonstrates the ability of wild-type influenza viruses to infect and replicate within two crocodilian substrates and suggests the need for further research to assess crocodilians as a species potentially susceptible to influenza virus infection. PMID:25380354

  7. Effect of nitrogen dioxide exposure on susceptibility to influenza A virus infection in healthy adults

    SciTech Connect

    Goings, S.A.; Kulle, T.J.; Bascom, R.; Sauder, L.R.; Green, D.J.; Hebel, J.R.; Clements, M.L.

    1989-05-01

    The effect of NO/sub 2/ exposure and human susceptibility to respiratory virus infection was investigated in a placebo-controlled, randomized, double-blind trial conducted in an environmentally controlled research chamber over 3 yr. Healthy, nonsmoking, young adult volunteers who were seronegative to influenza A/Korea/82 (H/sub 3/N/sub 2/) virus were randomly assigned to breathe either filtered clean air (control group) or NO/sub 2/ for 2 h/day for 3 consecutive days. The NO/sub 2/ concentrations were 2 ppm (Year 1), 3 ppm (Year 2), and 1 or 2 ppm (Year 3). Live, attenuated cold-adapted (ca) influenza A/Korea/82 reassortant virus was administered intranasally to all subjects immediately after the second exposure. Only one of the 152 volunteers had any symptoms; this person had a low grade fever. Pulmonary function measurements and nonspecific airway reactivity to methacholine were unchanged after NO/sub 2/ exposure, virus infection, or both. Infection was determined by virus recovery, a fourfold or greater increase in serum or nasal wash influenza-specific antibody titers, or both. The infection rates of the groups were 12/21 (2 ppm NO/sub 2/) versus 15/23 (clean air) in Year 1, 17/22 (3 ppm NO/sub 2/) versus 15/21 (clean air) in Year 2, and 20/22 (2 ppm) and 20/22 (1 ppm) versus 15/21 (clean air) in Year 3. Each group exposed to 1 or 2 ppm NO2 in the last year became infected more often (91%) than did the control group (71%), but the differences were not statistically significant.

  8. Antiviral responses of human Leydig cells to mumps virus infection or poly I:C stimulation

    PubMed Central

    Le Tortorec, A.; Denis, H.; Satie, A-P.; Patard, J-J.; Ruffault, A.; Jégou, B.; Dejucq-Rainsford, N.

    2008-01-01

    BACKGROUND The immuno-privileged status of the testis is essential to the maintenance of its functions, and innate immunity is likely to play a key role in limiting harmful viral infections, as demonstrated in the rat. In men mumps virus infects Leydig cells and has deleterious effects on testosterone production and spermatogenesis. The aim of this study was to test whether mumps virus infection of isolated human Leydig cells was associated with an inhibition of their innate antiviral defences. METHODS Leydig cell production of mRNA and protein for interferons (IFNs) and of three antiviral proteins—2′5′ oligoadenylate synthetase (2′5′OAS), double-stranded RNA-activated protein kinase (PKR) and MxA—was investigated, in the absence or presence of mumps virus or viral stimuli including poly I:C, a mimetic of RNA viruses replication product. RESULTS Stimulated or not, human Leydig cells appeared unable to produce routinely detectable IFNs α, β and γ. Although the level of PKR remained unchanged after stimulation, the expression of 2′5′OAS and MxA was enhanced following either mumps virus or poly I:C exposure (P < 0.05 versus control). CONCLUSIONS Overall, our results demonstrate that mumps virus replication in human Leydig cells is not associated with a specific inhibition of IFNs or 2′5′OAS, MxA and PKR production and that these cells display relatively weak endogenous antiviral abilities, as opposed to their rat counterparts. PMID:18567898

  9. Analysis of in vivo dynamics of influenza virus infection in mice using a GFP reporter virus

    PubMed Central

    Manicassamy, Balaji; Manicassamy, Santhakumar; Belicha-Villanueva, Alan; Pisanelli, Giuseppe; Pulendran, Bali; García-Sastre, Adolfo

    2010-01-01

    Influenza A virus is being extensively studied because of its major impact on human and animal health. However, the dynamics of influenza virus infection and the cell types infected in vivo are poorly understood. These characteristics are challenging to determine, partly because there is no efficient replication-competent virus expressing an easily traceable reporter gene. Here, we report the generation of a recombinant influenza virus carrying a GFP reporter gene in the NS segment (NS1-GFP virus). Although attenuated when compared with wild-type virus, the NS1-GFP virus replicates efficiently in murine lungs and shows pathogenicity in mice. Using whole-organ imaging and flow cytometry, we have tracked the dynamics of influenza virus infection progression in mice. Imaging of murine lungs shows that infection starts in the respiratory tract in areas close to large conducting airways and later spreads to deeper sections of the lungs. In addition to epithelial cells, we found GFP-positive antigen-presenting cells, such as CD11b+CD11c−, CD11b−CD11c+, and CD11b+CD11c+, as early as 24 h after intranasal infection. In addition, a significant proportion of NK and B cells were GFP positive, suggesting active infection of these cells. We next tested the effects of the influenza virus inhibitors oseltamivir and amantadine on the kinetics of in vivo infection progression. Treatment with oseltamivir dramatically reduced influenza infection in all cell types, whereas, surprisingly, amantadine treatment more efficiently blocked infection in B and NK cells. Our results demonstrate high levels of immune cells harboring influenza virus antigen during viral infection and cell-type–specific effects upon treatment with antiviral agents, opening additional avenues of research in the influenza virus field. PMID:20534532

  10. Role of oxidative stress in rabies virus infection of adult mouse dorsal root ganglion neurons.

    PubMed

    Jackson, Alan C; Kammouni, Wafa; Zherebitskaya, Elena; Fernyhough, Paul

    2010-05-01

    Rabies virus infection of dorsal root ganglia (DRG) was studied in vitro with cultured adult mouse DRG neurons. Recent in vivo studies of transgenic mice that express the yellow fluorescent protein indicate that neuronal process degeneration, involving both dendrites and axons, occurs in mice infected with the challenge virus standard (CVS) strain of rabies virus by footpad inoculation. Because of the similarities of the morphological changes in experimental rabies and in diabetic neuropathy and other diseases, we hypothesize that neuronal process degeneration occurs as a result of oxidative stress. DRG neurons were cultured from adult ICR mice. Two days after plating, they were infected with CVS. Immunostaining was evaluated with CVS- and mock-infected cultures for neuron specific beta-tubulin, rabies virus antigen, and amino acid adducts of 4-hydroxy-2-nonenal (4-HNE) (marker of lipid peroxidation and hence oxidative stress). Neuronal viability (by trypan blue exclusion), terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, and axonal growth were also assessed with the cultures. CVS infected 33 to 54% of cultured DRG neurons. Levels of neuronal viability and TUNEL staining were similar in CVS- and mock-infected DRG neurons. There were significantly more 4-HNE-labeled puncta at 2 and 3 days postinfection in CVS-infected cultures than in mock-infected cultures, and axonal outgrowth was reduced at these time points in CVS infection. Axonal swellings with 4-HNE-labeled puncta were also associated with aggregations of actively respiring mitochondria. We have found evidence that rabies virus infection in vitro causes axonal injury of DRG neurons through oxidative stress. Oxidative stress may be important in vivo in rabies and may explain previous observations of the degeneration of neuronal processes. PMID:20181692

  11. Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

    SciTech Connect

    Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R.

    2014-07-25

    Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.

  12. Evaluation of Diagnostic Markers for Measles Virus Infection in the Context of an Outbreak in Spain

    PubMed Central

    Mosquera, María M.; de Ory, Fernando; Gallardo, Virtudes; Cuenca, Loreto; Morales, Mercedes; Sánchez-Yedra, Waldo; Cabezas, Teresa; Hernández, Juan M.; Echevarría, Juan E.

    2005-01-01

    A measles outbreak occurred from January to July 2003 in Spain, despite the fact that the Plan of Eradication of Measles and its surveillance program had been set up in 2001. Different diagnostic markers for measles virus infection were compared for 246 patients in tests of serum, urine, and pharyngeal exudate specimens. Measles virus immunoglobulin M (IgM) and IgG and rubella virus and parvovirus IgM levels in serum were assayed. Multiplex PCR was done on urine, serum, and pharyngeal exudates, and isolation of measles virus in the B95a cell line from urine was attempted. At least one positive marker for measles virus was obtained from 165 patients (67.1%; total number of patients, 246). A total of 136 cases (82.4% of the patients showing positive markers) were diagnosed by PCR and/or isolation and IgM detection methods. The results for 27 patients (16.4%) were positive only by direct methods. The results for two patients (1.2%) were positive only by IgM detection. In the case of the first group (136 cases), the time elapsed from appearance of the rash was significantly longer than in the case of the group which was only positive by PCR. Besides, 8 out of 27 PCR-positive IgM-negative cases showed specific IgG results, suggesting either secondary vaccine failure or reinfection. Numbers resulting from PCR performed with pharyngeal exudates proved to be significantly higher than those obtained with other specimens. Phylogenetic analysis showed the presence of genotype B3. The results strongly back the World Health Organization recommendation that detection of IgM should be supplemented by PCR and isolation for the diagnosis of measles virus infection. PMID:16207972

  13. Cowpox virus infection in natural field vole Microtus agrestis populations: significant negative impacts on survival

    PubMed Central

    Burthe, Sarah; Telfer, Sandra; Begon, Michael; Bennett, Malcolm; Smith, Andrew; Lambin, Xavier

    2010-01-01

    Summary Cowpox virus is an endemic virus circulating in populations of wild rodents. It has been implicated as a potential cause of population cycles in field voles Microtus agrestis L., in Britain, owing to a delayed density-dependent pattern in prevalence, but its impact on field vole demographic parameters is unknown. This study tests the hypothesis that wild field voles infected with cowpox virus have a lower probability of survival than uninfected individuals. The effect of cowpox virus infection on the probability of an individual surviving to the next month was investigated using longitudinal data collected over 2 years from four grassland sites in Kielder Forest, UK. This effect was also investigated at the population level, by examining whether infection prevalence explained temporal variation in survival rates, once other factors influencing survival had been controlled for. Individuals with a probability of infection, P(I), of 1 at a time when base survival rate was at median levels had a 22·4% lower estimated probability of survival than uninfected individuals, whereas those with a P(I) of 0·5 had a 10·4% lower survival. At the population level, survival rates also decreased with increasing cowpox prevalence, with lower survival rates in months of higher cowpox prevalence. Simple matrix projection models with 28 day time steps and two stages, with 71% of voles experiencing cowpox infection in their second month of life (the average observed seroprevalence at the end of the breeding season) predict a reduction in 28-day population growth rate during the breeding season from λ = 1·62 to 1·53 for populations with no cowpox infection compared with infected populations. This negative correlation between cowpox virus infection and field vole survival, with its potentially significant effect on population growth rate, is the first for an endemic pathogen in a cyclic population of wild rodents. PMID:18177331

  14. [Novel treatments for hepatitis C virus infection in chronic kidney disease].

    PubMed

    Fabrizi, Fabrizio; Messa, Piergiorgio

    2016-01-01

    Recent evidence has been accumulated showing a negative impact of chronic hepatitis C virus infection on survival in patients with chronic kidney disease. Moreover, it appears that anti-HCV positive status has been associated with an increased risk of developing chronic kidney disease in the adult general population. These reports have emphasized the need for safe and effective therapies for hepatitis C virus infection in the chronic kidney disease population. Treatment of HCV has made considerable progress with the approval of interferon-free, direct-acting antiviral drug-based combination therapies among patients with intact kidneys; but a paucity of information exists regarding chronic kidney disease patients. The first published report on the antiviral treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 concerns the combination of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor); excellent safety and efficacy (sustained viral response, 94.3% 115/122) have been reached. In another study, the 3-D regimen (ombitasvir/ paritaprevir/ ritonavir/ dasabuvir with or without ribavirin) has been administered to CKD (stage 4-5) patients with genotype 1 (n=20); the rate of sustained viral response was excellent (90%, 18/20) and no patients discontinued treatment due to adverse events. Preliminary data on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89% (34/38), but the size of the study group (n=38 patients with end-stage renal disease) was small. Thus, the evidence in the medical literature concerning use of DAAs in CKD population is encouraging even if it has a preliminary nature. Also, several points need to be addressed regarding the use of DAAs in CKD population including their impact on survival, costs, and drug-drug interactions. PMID:27545640

  15. Modulation of flavonoid biosynthetic pathway genes and anthocyanins due to virus infection in grapevine (Vitis vinifera L.) leaves

    PubMed Central

    2010-01-01

    Background Symptoms of grapevine leafroll disease (GLRD) in red-fruited wine grape (Vitis vinifera L.) cultivars consist of green veins and red and reddish-purple discoloration of inter-veinal areas of leaves. The reddish-purple color of symptomatic leaves may be due to the accumulation of anthocyanins and could reflect an up-regulation of genes involved in their biosynthesis. Results We examined six putative constitutively expressed genes, Ubiquitin, Actin, GAPDH, EF1-a, SAND and NAD5, for their potential as references for normalization of gene expression in reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Using the geNorm program, a combination of two genes (Actin and NAD5) was identified as the stable set of reference genes for normalization of gene expression data obtained from grapevine leaves. By using gene-specific RT-qPCR in combination with a reliable normalization factor, we compared relative expression of the flavonoid biosynthetic pathway genes between leaves infected with Grapevine leafroll-associated virus 3 (GLRaV-3) and exhibiting GLRD symptoms and virus-free green leaves obtained from a red-fruited wine grape cultivar (cv. Merlot). The expression levels of these different genes ranged from two- to fifty-fold increase in virus-infected leaves. Among them, CHS3, F3'5'H, F3H1, LDOX, LAR1 and MybA1 showed greater than 10-fold increase suggesting that they were expressed at significantly higher levels in virus-infected symptomatic leaves. HPLC profiling of anthocyanins extracted from leaves indicated the presence of cyanidin-3-glucoside and malvidin-3-glucoside only in virus-infected symptomatic leaves. The results also showed 24% higher levels of flavonols in virus-infected symptomatic leaves than in virus-free green leaves, with quercetin followed by myricetin being the predominant compounds. Proanthocyanidins, estimated as total tannins by protein precipitation method, were 36% higher in virus-infected symptomatic

  16. The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java

    PubMed Central

    Kosasih, Herman; Alisjahbana, Bachti; Nurhayati; de Mast, Quirijn; Rudiman, Irani F.; Widjaja, Susana; Antonjaya, Ungke; Novriani, Harli; Susanto, Nugroho H.; Jusuf, Hadi; van der Ven, Andre; Beckett, Charmagne G.; Blair, Patrick J.; Burgess, Timothy H.; Williams, Maya; Porter, Kevin R.

    2016-01-01

    Background Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies. Methodology/Principal Findings Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000–2004 and 2006–2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%). The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case) and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections. Conclusions/Significance Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with

  17. CD8+ T cells control Ross River virus infection in musculoskeletal tissues of infected mice

    PubMed Central

    Burrack, Kristina S.; Montgomery, Stephanie A.; Homann, Dirk; Morrison, Thomas E.

    2014-01-01

    Ross River virus (RRV), chikungunya virus (CHIKV), and related alphaviruses cause debilitating polyarthralgia and myalgia. Mouse models of RRV and CHIKV have demonstrated a role for the adaptive immune response in the control of these infections. However, questions remain regarding the role for T cells in viral control, including the magnitude, location, and dynamics of CD8+ T cell responses. To address these questions, we generated a recombinant RRV expressing the H-2b-restricted gp33 determinant derived from the glycoprotein (gp) of lymphocytic choriomeningitis virus (LCMV) (“RRV-LCMV”). Utilizing tetramers, we tracked gp33-specific CD8+ T cells during RRV-LCMV infection. We found that acute RRV infection induces activation of CD8+ T cell responses in lymphoid and musculoskeletal tissues that peak from 10 to 14 days post-inoculation (dpi), suggesting that CD8+ T cells contribute to control of acute RRV infection. Mice genetically deficient for CD8+ T cells or wild-type mice depleted of CD8+ T cells had elevated RRV loads in skeletal muscle tissue, but not joint-associated tissues, at 14 dpi, suggesting that the ability of CD8+ T cells to control RRV infection is tissue-dependent. Finally, adoptively transferred T cells were capable of reducing RRV loads in skeletal muscle tissue of Rag1−/− mice, indicating that T cells can contribute to the control of RRV infection in the absence of B cells and antibody. Collectively, these data demonstrate a role for T cells in the control of RRV infection and suggest that the antiviral capacity of T cells is controlled in a tissue-specific manner. PMID:25488988

  18. Virus Infections Incite Pain Hypersensitivity by Inducing Indoleamine 2,3 Dioxygenase

    PubMed Central

    Huang, Lei; Ou, Rong; Rabelo de Souza, Guilherme; Cunha, Thiago M.; Lemos, Henrique; Mohamed, Eslam; Li, Lingqian; Pacholczyk, Gabriela; Randall, Janice; Munn, David H.; Mellor, Andrew L.

    2016-01-01

    expressing IDO in host responses to MuLV infection that enhance pain hypersensitivity and cause immune pathology. Collectively, our findings support the hypothesis elevated IDO activity in non-CNS due to virus infections causes pain hypersensitivity mediated by Kyn. Previously unappreciated links between host immune responses to virus infections and pain sensitivity suggest that IDO inhibitors may alleviate heightened pain sensitivity during infections. PMID:27168185

  19. Occult Hepatitis C Virus Infection in Hemodialysis Patients; Single Center Study

    PubMed Central

    El-shishtawy, Samya; Sherif, Nevine; Abdallh, Emad; Kamel, Laila; Shemis, Mohamed; Saleem, Abdel Aziz Ali; Abdalla, Haitham; el Din, Hesham Gamal

    2015-01-01

    Introduction A new form of hepatitis C virus infection, known as occult hepatitis C virus (HCV) infection, is characterized by the presence of HCV_RNA in the liver or peripheral blood mononuclear cells (PBMCs). However, no serological markers of infection occur and there is not as much damage to the liver damage as is produced by chronic hepatitis C. There is a high incidence of HCV infection among hemodialysis patients, there is significant concern about viral transmission. HCV infection is a major problem in hemodialysis (HD) units even though blood products are screened for anti-HCV antibodies and other precautions are taken. The aim of this study was to determine the prevalence of occult HCV infection in PBMC in chronic hemodialysis (CHD) patients in the dialysis unit at Theodor Bilharz Research Institute (TBRI) with HCV antibodies and HCV RNA negativity irrespective of their liver function tests. Methods Fifty-three patients who were repeatedly were anti-HCV negative and serum HCV-RNA negative and on regular hemodialysis for > six months were enrolled in the study, which was conducted in the dialysis unit of Nephrology Department at TBRI; there were 10 healthy matched controls. The patients were classified into two groups according to the result HCV RNA in their PBMCs. Serological markers of HCV infection, including anti-HCV antibody and serum HCV-RNA, were repeatedly negative for all patients included in the study. We collected serum and PBMC samples from the patients on the day they entered the study. The test of all serum samples for anti-HCV antibodies and HCV-RNA was repeated by RT-PCR to ensure that the patients did not have these HCV serologic markers, We also measured their ALT and GGT levels. Results Occult hepatitis C virus infection (OCI) was detected in 15.1% of our CHD patients without any evidence of chronic liver disease. Conclusion Occult HCV infection was present among the hemodialysis patients irrespective of whether they had persistent

  20. Virus Infections Incite Pain Hypersensitivity by Inducing Indoleamine 2,3 Dioxygenase.

    PubMed

    Huang, Lei; Ou, Rong; Rabelo de Souza, Guilherme; Cunha, Thiago M; Lemos, Henrique; Mohamed, Eslam; Li, Lingqian; Pacholczyk, Gabriela; Randall, Janice; Munn, David H; Mellor, Andrew L

    2016-05-01

    expressing IDO in host responses to MuLV infection that enhance pain hypersensitivity and cause immune pathology. Collectively, our findings support the hypothesis elevated IDO activity in non-CNS due to virus infections causes pain hypersensitivity mediated by Kyn. Previously unappreciated links between host immune responses to virus infections and pain sensitivity suggest that IDO inhibitors may alleviate heightened pain sensitivity during infections. PMID:27168185

  1. Clinical aspects and cytokine response in severe H1N1 influenza A virus infection

    PubMed Central

    2010-01-01

    Introduction The immune responses in patients with novel A(H1N1) virus infection (nvA(H1N1)) are incompletely characterized. We investigated the profile of Th1 and Th17 mediators and interferon-inducible protein-10 (IP-10) in groups with severe and mild nvA(H1N1) disease and correlated them with clinical aspects. Methods Thirty-two patients hospitalized with confirmed nvA(H1N1) infection were enrolled in the study: 21 patients with nvA(H1N1)-acute respiratory distress syndrome (ARDS) and 11 patients with mild disease. One group of 20 patients with bacterial sepsis-ARDS and another group of 15 healthy volunteers were added to compare their cytokine levels with pandemic influenza groups. In the nvA(H1N1)-ARDS group, the serum cytokine samples were obtained on admission and 3 days later. The clinical aspects were recorded prospectively. Results In the nvA(H1N1)-ARDS group, obesity and lymphocytopenia were more common and IP-10, interleukin (IL)-12, IL-15, tumor necrosis factor (TNF)α, IL-6, IL-8 and IL-9 were significantly increased versus control. When comparing mild with severe nvA(H1N1) groups, IL-6, IL-8, IL-15 and TNFα were significantly higher in the severe group. In nonsurvivors versus survivors, IL-6 and IL-15 were increased on admission and remained higher 3 days later. A positive correlation of IL-6, IL-8 and IL-15 levels with C-reactive protein and with > 5-day interval between symptom onset and admission, and a negative correlation with the PaO2:FiO2 ratio, were found in nvA(H1N1) groups. In obese patients with influenza disease, a significant increased level of IL-8 was found. When comparing viral ARDS with bacterial ARDS, the level of IL-8, IL-17 and TNFα was significantly higher in bacterial ARDS and IL-12 was increased only in viral ARDS. Conclusions In our critically ill patients with novel influenza A(H1N1) virus infection, the hallmarks of the severity of disease were IL-6, IL-15, IL-8 and TNFα. These cytokines, except TNFα, had a positive

  2. Little Evidence of Subclinical Avian Influenza Virus Infections among Rural Villagers in Cambodia

    PubMed Central

    Gray, Gregory C.; Krueger, Whitney S.; Chum, Channimol; Putnam, Shannon D.; Wierzba, Thomas F.; Heil, Gary L.; Anderson, Benjamin D.; Yasuda, Chadwick Y.; Williams, Maya; Kasper, Matthew R.; Saphonn, Vonthanak; Blair, Patrick J.

    2014-01-01

    In 2008, 800 adults living within rural Kampong Cham Province, Cambodia were enrolled in a prospective cohort study of zoonotic influenza transmission. After enrollment, participants were contacted weekly for 24 months to identify acute influenza-like illnesses (ILI). Follow-up sera were collected at 12 and 24 months. A transmission substudy was also conducted among the family contacts of cohort members reporting ILI who were influenza A positive. Samples were assessed using serological or molecular techniques looking for evidence of infection with human and avian influenza viruses. Over 24 months, 438 ILI investigations among 284 cohort members were conducted. One cohort member was hospitalized with a H5N1 highly pathogenic avian influenza (HPAI) virus infection and withdrew from the study. Ninety-seven ILI cases (22.1%) were identified as influenza A virus infections by real-time RT-PCR; none yielded evidence for AIV. During the 2 years of follow-up, 21 participants (3.0%) had detectable antibody titers (≥1∶10) against the studied AIVs: 1 against an avian-like A/Migratory duck/Hong Kong/MPS180/2003(H4N6), 3 against an avian-like A/Teal/Hong Kong/w312/97(H6N1), 9 (3 of which had detectible antibody titers at both 12- and 24-month follow-up) against an avian-like A/Hong Kong/1073/1999(H9N2), 6 (1 detected at both 12- and 24-month follow-up) against an avian-like A/Duck/Memphis/546/74(H11N9), and 2 against an avian-like A/Duck/Alberta/60/76(H12N5). With the exception of the one hospitalized cohort member with H5N1 infection, no other symptomatic avian influenza infections were detected among the cohort. Serological evidence for subclinical infections was sparse with only one subject showing a 4-fold rise in microneutralization titer over time against AvH12N5. In summary, despite conducting this closely monitored cohort study in a region enzootic for H5N1 HPAI, we were unable to detect subclinical avian influenza infections, suggesting either that these

  3. Losartan and enalapril decrease viral absorption and interleukin 1 beta production by macrophages in an experimental dengue virus infection.

    PubMed

    Hernández-Fonseca, Juan Pablo; Durán, Anyelo; Valero, Nereida; Mosquera, Jesús

    2015-11-01

    The role of angiotensin II (Ang II) in dengue virus infection remains unknown. The aim of this study was to determine the effect of losartan, an antagonist of the angiotensin II type 1 receptor (AT1 receptor), and enalapril, an inhibitor of angiotensin I-converting enzyme (ACE), on viral antigen expression and IL-1β production in peritoneal macrophages infected with dengue virus type 2. Mice treated with losartan or enalapril and untreated controls were infected intraperitoneally with the virus, and macrophages were analyzed. Infection resulted in increased IL-1β production and a high percentage of cells expressing viral antigen, and this was decreased by treatment with anti-Ang II drugs, suggesting a role for Ang II in dengue virus infection. PMID:26321474

  4. Risk factors for hepatitis B virus infection in black female attendees of a sexually transmitted disease clinic.

    PubMed

    Baddour, L M; Bucak, V A; Somes, G; Hudson, R

    1988-01-01

    Although recent data have supported the role of heterosexual activity in the transmission of hepatitis B virus infection in women, studies generating these data have enrolled few black women. We therefore examined black female participants attending our local health department's sexually transmitted disease clinic for the treatment of presumed uncomplicated gonorrhea in serologic and risk-factor surveys of hepatitis B virus infection. Twenty-four (17.6%) of 136 subjects tested had evidence of prior hepatitis B infection. Serologic evidence of hepatitis B infection was significantly associated with three different barometers of sexual activity that included: (1) years of sexual activity (P less than 0.005); (2) history of sexually transmitted disease (P less than 0.02); and (3) number of lifetime heterosexual partners (P less than 0.001). These data provide further support that the quantity of sexual exposure seems to be an important risk factor for hepatitis B infection in heterosexually active females. PMID:3227474

  5. Outbreak of hepatitis C virus infections at an outpatient hemodialysis facility: the importance of infection control competencies.

    PubMed

    Rao, Agam K; Luckman, Emily; Wise, Matthew E; MacCannell, Taranisia; Blythe, David; Lin, Yulin; Xia, Guoliang; Drobeniuc, Jan; Noble-Wang, Judith; Arduino, Matthew J; Thompson, Nicola D; Patel, Priti R; Wilson, Lucy E

    2013-01-01

    In the United States, the prevalence of hepatitis C virus infection among patients treated in hemodialysis facilities is five times higher than among the general population. This study investigated eight new hepatitis C virus infections among patients treated at an outpatient hemodialysis facility. Epidemiologic investigation and viral sequencing demonstrated that transmission likely occurred between patients typically treated during the same or consecutive shifts at the same or a nearby station. Several infection control breaches were observed including lapses involving the preparation, handling, and administration of parenteral medications. Improved infection control education and training for all hemodialysis facility staff is an important component of assuring adherence to appropriate procedures and preventing future outbreaks. PMID:23785746

  6. The Role of Plasmacytoid Dendritic Cells in Innate and Adaptive Immune Responses against Alpha Herpes Virus Infections

    PubMed Central

    Schuster, Philipp; Boscheinen, Jan Bernardin; Tennert, Karin; Schmidt, Barbara

    2011-01-01

    In 1999, two independent groups identified plasmacytoid dendritic cells (PDC) as major type I interferon- (IFN-) producing cells in the blood. Since then, evidence is accumulating that PDC are a multifunctional cell population effectively coordinating innate and adaptive immune responses. This paper focuses on the role of different immune cells and their interactions in the surveillance of alpha herpes virus infections, summarizes current knowledge on PDC surface receptors and their role in direct cell-cell contacts, and develops a risk factor model for the clinical implications of herpes simplex and varicella zoster virus reactivation. Data from studies involving knockout mice and cell-depletion experiments as well as human studies converge into a “spider web”, in which the direct and indirect crosstalk between many cell populations tightly controls acute, latent, and recurrent alpha herpes virus infections. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses more extensively than previously thought. PMID:22312349

  7. Mitogen responsiveness after exposure of influenza virus-infected human mononuclear leukocytes to continuous or pulse-modulated radiofrequency radiation

    SciTech Connect

    Roberts, N.J. Jr.; Michaelson, S.M.; Lu, S.T.

    1987-06-01

    Data are available regarding interactions of radiofrequency radiation (RFR) with normal human mononuclear leukocytes. However, no data have emerged regarding effects of RFR on human leukocytes already challenged by a commonly encountered alternate agent, such as a virus. Therefore, in these studies, uninfected (control) and in vitro influenza virus-infected human mononuclear leukocytes were exposed to 2450 MHz RFR as continuous waves or pulse-modulated at 60 or 16 Hz, at a specific absorption rate of 4 mW/ml. Such exposures produced no significant effects on leukocyte viability or on mitogen-stimulated DNA synthesis by either uninfected or influenza virus-infected leukocytes when compared to sham-RFR-exposed of cells.

  8. Genetic changes in grapevine genomes after stress induced by in vitro cultivation, thermotherapy and virus infection, as revealed by AFLP

    PubMed Central

    2009-01-01

    The Amplification Fragment Length Polymorphism (AFLP) technique was employed to study genetic variations which can be induced in vines by the stress occurring during different aspects of viticulture (in vitro cultivation, in vitro thermotherapy and virus infection). Analysis of AFLP banding patterns, generated by using 15 primer combinations, pointed to negligible genetic variation among plants exposed to individual stress. The average of similarity coefficients between differently stressed plants of the cultivars Müller Thurgau and Riesling were 0.984 and 0.991, respectively, as revealed by AFLP analysis. The low incidence of observed polymorphism demonstrates the high level of genome uniformity in plants reproduced by in vitro micropropagation via nodes, those subjected to in vitro thermotherapy and virus-infected plants. PMID:21637461

  9. Avian Influenza A(H7N9) Virus Infection in 2 Travelers Returning from China to Canada, January 20151

    PubMed Central

    Chambers, Catharine; Gustafson, Reka; Purych, Dale B.; Tang, Patrick; Bastien, Nathalie; Krajden, Mel; Li, Yan

    2016-01-01

    In January 2015, British Columbia, Canada, reported avian influenza A(H7N9) virus infection in 2 travelers returning from China who sought outpatient care for typical influenza-like illness. There was no further spread, but serosurvey findings showed broad population susceptibility to H7N9 virus. Travel history and timely notification are critical to emerging pathogen detection and response. PMID:26689320

  10. Exacerbation of Influenza Virus Infections in Mice by Intranasal Treatments and Implications for Evaluation of Antiviral Drugs

    PubMed Central

    von Itzstein, Mark; Bhatt, Beenu; Tarbet, E. Bart

    2012-01-01

    Compounds lacking oral activity may be delivered intranasally to treat influenza virus infections in mice. However, intranasal treatments greatly enhance the virulence of such virus infections. This can be partially compensated for by giving reduced virus challenge doses. These can be 100- to 1,000-fold lower than infections without such treatment and still cause equivalent mortality. We found that intranasal liquid treatments facilitate virus production (probably through enhanced virus spread) and that lung pneumonia was delayed by only 2 days relative to a 1,000-fold higher virus challenge dose not accompanied by intranasal treatments. In one study, zanamivir was 90 to 100% effective at 10 mg/kg/day by oral, intraperitoneal, and intramuscular routes against influenza A/California/04/2009 (H1N1) virus in mice. However, the same compound administered intranasally at 20 mg/kg/day for 5 days gave no protection from death although the time to death was significantly delayed. A related compound, Neu5Ac2en (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid), was ineffective at 100 mg/kg/day. Intranasal zanamivir and Neu5Ac2en were 70 to 100% protective against influenza A/NWS/33 (H1N1) virus infections at 0.1 to 10 and 30 to 100 mg/kg/day, respectively. Somewhat more difficult to treat was A/Victoria/3/75 virus that required 10 mg/kg/day of zanamivir to achieve full protection. These results illustrate that treatment of influenza virus infections by the intranasal route requires consideration of both virus challenge dose and virus strain in order to avoid compromising the effectiveness of a potentially useful antiviral agent. In addition, the intranasal treatments were shown to facilitate virus replication and promote lung pathology. PMID:23027194

  11. Zika virus infections in three travellers returning from South America and the Caribbean respectively, to Montpellier, France, December 2015 to January 2016.

    PubMed

    Maria, Alexandre Thibault; Maquart, Marianne; Makinson, Alain; Flusin, Olivier; Segondy, Michel; Leparc-Goffart, Isabelle; Le Moing, Vincent; Foulongne, Vincent

    2016-01-01

    We report three unrelated cases of Zika virus infection in patients returning from Martinique, Brazil and Colombia respectively, to Montpellier, France. They developed symptoms compatible with a mosquito-borne disease, and serological and molecular investigations indicated a recent Zika virus infection. Considering the recent warning for the likely teratogenicity of Zika virus and the presence of competent mosquito vectors in southern France, these cases highlight the need for awareness of physicians and laboratories in Europe. PMID:26898198

  12. Antiviral Responses by Swine Primary Bronchoepithelial Cells Are Limited Compared to Human Bronchoepithelial Cells Following Influenza Virus Infection

    PubMed Central

    Hauser, Mary J.; Dlugolenski, Daniel; Culhane, Marie R.; Wentworth, David E.; Tompkins, S. Mark; Tripp, Ralph A.

    2013-01-01

    Swine generate reassortant influenza viruses because they can be simultaneously infected with avian and human influenza; however, the features that restrict influenza reassortment in swine and human hosts are not fully understood. Type I and III interferons (IFNs) act as the first line of defense against influenza virus infection of respiratory epithelium. To determine if human and swine have different capacities to mount an antiviral response the expression of IFN and IFN-stimulated genes (ISG) in normal human bronchial epithelial (NHBE) cells and normal swine bronchial epithelial (NSBE) cells was evaluated following infection with human (H3N2), swine (H1N1), and avian (H5N3, H5N2, H5N1) influenza A viruses. Expression of IFNλ and ISGs were substantially higher in NHBE cells compared to NSBE cells following H5 avian influenza virus infection compared to human or swine influenza virus infection. This effect was associated with reduced H5 avian influenza virus replication in human cells at late times post infection. Further, RIG-I expression was lower in NSBE cells compared to NHBE cells suggesting reduced virus sensing. Together, these studies identify key differences in the antiviral response between human and swine respiratory epithelium alluding to differences that may govern influenza reassortment. PMID:23875024

  13. Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection - United States, 2016.

    PubMed

    Staples, J Erin; Dziuban, Eric J; Fischer, Marc; Cragan, Janet D; Rasmussen, Sonja A; Cannon, Michael J; Frey, Meghan T; Renquist, Christina M; Lanciotti, Robert S; Muñoz, Jorge L; Powers, Ann M; Honein, Margaret A; Moore, Cynthia A

    2016-01-01

    CDC has developed interim guidelines for health care providers in the United States who are caring for infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy. These guidelines include recommendations for the testing and management of these infants. Guidance is subject to change as more information becomes available; the latest information, including answers to commonly asked questions, can be found online (http://www.cdc.gov/zika). Pediatric health care providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (based on travel to or residence in an area with Zika virus transmission [http://wwwnc.cdc.gov/travel/notices]), and review fetal ultrasounds and maternal testing for Zika virus infection (see Interim Guidelines for Pregnant Women During a Zika Virus Outbreak*) (1). Zika virus testing is recommended for 1) infants with microcephaly or intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant; or 2) infants born to mothers with positive or inconclusive test results for Zika virus infection. For infants with laboratory evidence of a possible congenital Zika virus infection, additional clinical evaluation and follow-up is recommended. Health care providers should contact their state or territorial health department to facilitate testing. As an arboviral disease, Zika virus disease is a nationally notifiable condition. PMID:26820387

  14. E3 Ubiquitin Ligase NEDD4 Promotes Influenza Virus Infection by Decreasing Levels of the Antiviral Protein IFITM3

    PubMed Central

    Chesarino, Nicholas M.; McMichael, Temet M.; Yount, Jacob S.

    2015-01-01

    Interferon (IFN)-induced transmembrane protein 3 (IFITM3) is a cell-intrinsic factor that limits influenza virus infections. We previously showed that IFITM3 degradation is increased by its ubiquitination, though the ubiquitin ligase responsible for this modification remained elusive. Here, we demonstrate that the E3 ubiquitin ligase NEDD4 ubiquitinates IFITM3 in cells and in vitro. This IFITM3 ubiquitination is dependent upon the presence of a PPxY motif within IFITM3 and the WW domain-containing region of NEDD4. In NEDD4 knockout mouse embryonic fibroblasts, we observed defective IFITM3 ubiquitination and accumulation of high levels of basal IFITM3 as compared to wild type cells. Heightened IFITM3 levels significantly protected NEDD4 knockout cells from infection by influenza A and B viruses. Similarly, knockdown of NEDD4 in human lung cells resulted in an increase in steady state IFITM3 and a decrease in influenza virus infection, demonstrating a conservation of this NEDD4-dependent IFITM3 regulatory mechanism in mouse and human cells. Consistent with the known association of NEDD4 with lysosomes, we demonstrate for the first time that steady state turnover of IFITM3 occurs through the lysosomal degradation pathway. Overall, this work identifies the enzyme NEDD4 as a new therapeutic target for the prevention of influenza virus infections, and introduces a new paradigm for up-regulating cellular levels of IFITM3 independently of IFN or infection. PMID:26263374

  15. Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells

    PubMed Central

    Li, Hong; Xiang, Zheng; Feng, Ting; Li, Jinrong; Liu, Yinping; Fan, Yingying; Lu, Qiao; Yin, Zhongwei; Yu, Meixing; Shen, Chongyang; Tu, Wenwei

    2013-01-01

    γδ-T cells play an indispensable role in host defense against different viruses, including influenza A virus. However, whether these cells have cytotoxic activity against influenza virus-infected lung alveolar epithelial cells and subsequently contribute to virus clearance remains unknown. Using influenza virus-infected A549 cells, human lung alveolar epithelial cells, we investigated the cytotoxic activity of aminobisphosphonate pamidronate (PAM)-expanded human Vγ9Vδ2-T cells and their underlying mechanisms. We found that PAM could selectively activate and expand human Vγ9Vδ2-T cells. PAM-expanded human Vγ9Vδ2-T cells efficiently killed influenza virus-infected lung alveolar epithelial cells and inhibited virus replication. The cytotoxic activity of PAM-expanded Vγ9Vδ2-T cells was dependent on cell-to-cell contact and required NKG2D activation. Perforin–granzyme B, tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas–Fas ligand (FasL) pathways were involved in their cytotoxicity. Our study suggests that targeting γδ-T cells by PAM can potentially offer an alternative option for the treatment of influenza virus. PMID:23353835

  16. Molecular Signatures Associated with Mx1-Mediated Resistance to Highly Pathogenic Influenza Virus Infection: Mechanisms of Survival

    PubMed Central

    Cilloniz, Cristian; Pantin-Jackwood, Mary J.; Ni, Chester; Carter, Victoria S.; Korth, Marcus J.; Swayne, David E.; Tumpey, Terrence M.

    2012-01-01

    Understanding the role of host factors during lethal influenza virus infection is critical to deciphering the events that determine the fate of the host. One such factor is encoded by the Mx1 gene, which confers resistance to influenza virus infection. Here, we compared pathology and global gene expression profiles in lung tissue from BALB/c (Mx1−) and BALB · A2G-Mx1 mice (Mx1+/+) infected with the fully reconstructed 1918 pandemic influenza virus. Mx1+/+ mice showed less tissue damage than Mx− animals, and pathology and mortality were further reduced by treating the mice with interferon prior to infection. Using global transcriptional profiling, we identified distinct molecular signatures associated with partial protection, complete protection, and the contribution of interferon to the host response. In the absence of interferon treatment, partial protection was characterized by the generation of an acute response with the upregulation of genes associated with apoptosis, reactive oxygen species, and cell migration. Complete protection was characterized by the downregulation of cytokine and chemokine genes previously associated with influenza virus pathogenesis. The contribution of interferon treatment to total protection in virus-infected Mx1+/+ mice was characterized by the altered regulation of cell cycle genes. These genes were upregulated in Mx1+/+ mice treated with interferon but downregulated in the absence of interferon treatment. Our results suggest that Mx1+/+ mice generate a protective antiviral response by controlling the expression of key modulator molecules associated with influenza virus lethality. PMID:22190720

  17. Changes in the metabolome and histopathology of Amaranthus hypochondriacus L. in response to Ageratum enation virus infection.

    PubMed

    Srivastava, Shatakshi; Bisht, Hema; Sidhu, O P; Srivastava, Ashish; Singh, P C; Pandey, R M; Raj, S K; Roy, Raja; Nautiyal, C S

    2012-08-01

    Amaranthus hypochondriacus L. infected with Ageratum enation virus (AEV) was investigated for identifying alteration in the anatomical structures, sap translocation and metabolomic variations using light microscopy, magnetic resonance imaging, NMR spectroscopy and GC-MS, respectively. Combination of GC-MS and NMR spectroscopy identified 68 polar and non-polar metabolites that were present in different levels in healthy and virus-infected A. hypochondriacus. Contrast of T₁ and T₂ weighted MR images showed significant differences in the spatial distribution of water, lipids and macromolecules indicating alterations in the cortical region and disruption of vascular bundles in virus-infected stem tissues. MRI observations are supported by light microscopic examination. Microscopic examination of AEV infected stem revealed severe hyperplasia with a considerable reduction in size of stem cells. The NMR spectroscopy and GC-MS analysis indicated that viral infection significantly affected the plant primary and secondary metabolism resulting in decreased glucose and sucrose content and increase in the concentration of β-sitosterol and stigmasterol. Higher accumulation of TCA cycle intermediates such as citric acid and malic acid in AEV infected plants indicated enhanced rate of respiratory metabolism. The viral stress significantly increases the concentration of erythritol and myo-inositol as compared to healthy ones. Lower concentration of glucose and sucrose in viral-infected stem tissues suggests decreased translocation of photosynthates in the plants. The results demonstrated potential of MRI, NMR spectroscopy and GC-MS for studying anatomical and metabolic variations in virus-infected plants. PMID:22683210

  18. Ecologic risk factor investigation of clusters of avian influenza A (H5N1) virus infection in Thailand.

    PubMed

    Tiensin, Thanawat; Ahmed, Syed Sayeem Uddin; Rojanasthien, Suvichai; Songserm, Thaweesak; Ratanakorn, Parntep; Chaichoun, Kridsada; Kalpravidh, Wantanee; Wongkasemjit, Surapong; Patchimasiri, Tuangthong; Chanachai, Karoon; Thanapongtham, Weerapong; Chotinan, Suwit; Stegeman, Arjan; Nielen, Mirjam

    2009-06-15

    This study was conducted to investigate space and time clusters of highly pathogenic avian influenza A (H5N1) virus infection and to determine risk factors at the subdistrict level in Thailand. Highly pathogenic avian influenza A (H5N1) was diagnosed in 1890 poultry flocks located in 953 subdistricts during 2004-2007. The ecologic risk for H5N1 virus infection was assessed on the basis of a spatial-based case-control study involving 824 case subdistricts and 3296 control subdistricts from 6 study periods. Risk factors investigated in clustered areas of H5N1 included human and animal demographic characteristics, poultry production systems, and wild birds and their habitats. Six variables remained statistically significant in the final model: flock density of backyard chickens (odds ratio [OR], 0.98), flock density of fighting cocks (OR, 1.02), low and high human density (OR, 0.60), presence of quail flocks (OR, 1.21), free-grazing duck flocks (OR, 2.17), and a poultry slaughterhouse (OR, 1.33). We observed a strong association between subdistricts with H5N1 virus-infected poultry flocks and evidence of prior and concomitant H5N1 infection in wild birds in the same subdistrict. PMID:19416075

  19. Polymer-attached zanamivir inhibits synergistically both early and late stages of influenza virus infection.

    PubMed

    Lee, Chia Min; Weight, Alisha K; Haldar, Jayanta; Wang, Ling; Klibanov, Alexander M; Chen, Jianzhu

    2012-12-11

    Covalently conjugating multiple copies of the drug zanamivir (ZA; the active ingredient in Relenza) via a flexible linker to poly-l-glutamine (PGN) enhances the anti-influenza virus activity by orders of magnitude. In this study, we investigated the mechanisms of this phenomenon. Like ZA itself, the PGN-attached drug (PGN-ZA) binds specifically to viral neuraminidase and inhibits both its enzymatic activity and the release of newly synthesized virions from infected cells. Unlike monomeric ZA, however, PGN-ZA also synergistically inhibits early stages of influenza virus infection, thus contributing to the markedly increased antiviral potency. This inhibition is not caused by a direct virucidal effect, aggregation of viruses, or inhibition of viral attachment to target cells and the subsequent endocytosis; rather, it is a result of interference with intracellular trafficking of the endocytosed viruses and the subsequent virus-endosome fusion. These findings both rationalize the great anti-influenza potency of PGN-ZA and reveal that attaching ZA to a polymeric chain confers a unique mechanism of antiviral action potentially useful for minimizing drug resistance. PMID:23185023

  20. Reproducible selection of high avidity CD8+ T-cell clones following secondary acute virus infection

    PubMed Central

    Cukalac, Tania; Chadderton, Jesseka; Handel, Andreas; Doherty, Peter C.; Turner, Stephen J.; Thomas, Paul G.; La Gruta, Nicole L.

    2014-01-01

    The recall of memory CD8+ cytotoxic T lymphocytes (CTLs), elicited by prior virus infection or vaccination, is critical for immune protection. The extent to which this arises as a consequence of stochastic clonal expansion vs. active selection of particular clones remains unclear. Using a parallel adoptive transfer protocol in combination with single cell analysis to define the complementarity determining region (CDR) 3α and CDR3β regions of individual T-cell receptor (TCR) heterodimers, we characterized the antigen-driven recall of the same memory CTL population in three individual recipients. This high-resolution analysis showed reproducible enrichment (or diminution) of particular TCR clonotypes across all challenged animals. These changes in clonal composition were TCRα− and β chain–dependent and were directly related to the avidity of the TCR for the virus-derived peptide (p) + major histocompatibility complex class I molecule. Despite this shift in clonotype representation indicative of differential selection, there was no evidence of overall repertoire narrowing, suggesting a strategy to optimize CTL responses while safeguarding TCR diversity. PMID:24474775

  1. Characterisation of three novel giant viruses reveals huge diversity among viruses infecting Prymnesiales (Haptophyta).

    PubMed

    Johannessen, Torill Vik; Bratbak, Gunnar; Larsen, Aud; Ogata, Hiroyuki; Egge, Elianne S; Edvardsen, Bente; Eikrem, Wenche; Sandaa, Ruth-Anne

    2015-02-01

    We have isolated three novel lytic dsDNA-viruses from Raunefjorden (Norway) that are putative members of the Mimiviridae family, namely Haptolina ericina virus RF02 (HeV RF02), Prymnesium kappa virus RF01 (PkV RF01), and Prymnesium kappa virus RF02 (PkV RF02). Each of the novel haptophyte viruses challenges the common conceptions of algal viruses with respect to host range, phylogenetic affiliation and size. PkV RF01 has a capsid of ~310 nm and is the largest algal virus particle ever reported while PkV RF01 and HeV RF02 were able to infect different species, even belonging to different genera. Moreover, PkV RF01 and HeV RF02 infected the same hosts, but phylogenetic analysis placed them in different groups. Our results reveal large variation among viruses infecting closely related microalgae, and challenge the common conception that algal viruses have narrow host range, and phylogeny reflecting their host affiliation. PMID:25546253

  2. Propagation of viruses infecting waterfowl on continuous cell lines of Muscovy duck (Cairina moschata) origin.

    PubMed

    Mészáros, István; Tóth, Renáta; Bálint, Adám; Dán, Adám; Jordan, Ingo; Zádori, Zoltán

    2014-01-01

    Duck circovirus, duck hepatitis A virus 1, goose parvovirus and goose haemorrhagic polyomavirus are economically damaging pathogens of waterfowl, and replicate poorly or not at all in established cell lines. AGE1.CR, AGE1.CR.pIX and AGE1.CS cell lines, originating from the Muscovy duck, were tested for their suitability to isolate and identify these viruses. Immunofluorescence (IF) and quantitative polymerase chain reaction investigations verified that all cell lines are permissive for all four viruses; however, AGE1.CR.pIX proved to be the most productive and most sensitive for viral infection. IF experiments revealed that the time of one infectious cycle is approximately 12 to 14 h in the AGE1.CR.pIX cells in the case of the three DNA viruses, while it is 10 to 12 h for DHAV-1. Specific viral infectivity and the limit of detection by IF varied between 55 and 1484 copies, depending on the viruses and cell lines. Despite the high sensitivity of the cell lines for viruses, their viral productivity remained relatively low for the investigated field isolates. However, optimization of virus infection and/or the adaptation of the viruses to the cells can raise viral productivity and can make these cell lines suitable for vaccine development and production. PMID:24992264

  3. IL-21-producer CD4+ T cell kinetics during primary simian immunodeficiency virus infection.

    PubMed

    Shi, Shoi; Seki, Sayuri; Matano, Tetsuro; Yamamoto, Hiroyuki

    2013-01-01

    IL-21 signaling is important for T cell and B cell-mediated clearance of chronic viral infections. While non-cognate follicular helper CD4+ T cells (TFH) are indicated to be pivotal in providing IL-21-mediated help to activated B cells within germinal centers, how this signaling may be disrupted in early AIDS virus infection is not clear. In this study, we assessed the lineage and kinetics of peripheral blood IL-21-producing CD4+ T cells in primary simian immunodeficiency virus (SIV) infection of rhesus macaques. After SIV challenge, antigen-nonspecific IL-21 production was observed in Th1, Th2 and Th17 cells with Th1 dominance. While IL-21+ Th2 and IL-21+ Th17 showed variable kinetics, an increase in total IL-21+ CD4+ T cells and IL-21+ Th1 from week 3 to week 8 was observed, preceding plasma SIV-specific IgG development from week 5 to week 12. SIV Gag-specific IL-21+ CD4+ T cells detectable at week 2 were decreased in frequencies at week 5. Results imply that kinetics of IL-21+ CD4+ T cells comprised of multiple lineages, potentially targeted by SIV with a bias of existing frequencies during their precursor stage, associate with availability of cooperative B-cell help provided through a proportionate precursor pool developing into TFH and subsequent anti-SIV antibody responses. PMID:23791954

  4. Update on emerging antivirals for the management of herpes simplex virus infections: a patenting perspective.

    PubMed

    Vadlapudi, Aswani D; Vadlapatla, Ramya K; Mitra, Ashim K

    2013-04-01

    Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections. PMID:23331181

  5. Reproducible selection of high avidity CD8+ T-cell clones following secondary acute virus infection.

    PubMed

    Cukalac, Tania; Chadderton, Jesseka; Handel, Andreas; Doherty, Peter C; Turner, Stephen J; Thomas, Paul G; La Gruta, Nicole L

    2014-01-28

    The recall of memory CD8(+) cytotoxic T lymphocytes (CTLs), elicited by prior virus infection or vaccination, is critical for immune protection. The extent to which this arises as a consequence of stochastic clonal expansion vs. active selection of particular clones remains unclear. Using a parallel adoptive transfer protocol in combination with single cell analysis to define the complementarity determining region (CDR) 3α and CDR3β regions of individual T-cell receptor (TCR) heterodimers, we characterized the antigen-driven recall of the same memory CTL population in three individual recipients. This high-resolution analysis showed reproducible enrichment (or diminution) of particular TCR clonotypes across all challenged animals. These changes in clonal composition were TCRα- and β chain-dependent and were directly related to the avidity of the TCR for the virus-derived peptide (p) + major histocompatibility complex class I molecule. Despite this shift in clonotype representation indicative of differential selection, there was no evidence of overall repertoire narrowing, suggesting a strategy to optimize CTL responses while safeguarding TCR diversity. PMID:24474775

  6. Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection

    PubMed Central

    Martínez-Romero, Carles; Barrado-Gil, Lucía; Galindo, Inmaculada; García-Sastre, Adolfo; Alonso, Covadonga

    2016-01-01

    The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. While IFITMs are widely known to inhibit several single-stranded RNA viruses, there are limited reports available regarding their effect in double-stranded DNA viruses. In this work, we have analyzed a possible antiviral function of IFITMs against a double stranded DNA virus, the African swine fever virus (ASFV). Infection with cell-adapted ASFV isolate Ba71V is IFN sensitive and it induces IFITMs expression. Interestingly, high levels of IFITMs caused a collapse of the endosomal pathway to the perinuclear area. Given that ASFV entry is strongly dependent on endocytosis, we investigated whether IFITM expression could impair viral infection. Expression of IFITM1, 2 and 3 reduced virus infectivity in Vero cells, with IFITM2 and IFITM3 having an impact on viral entry/uncoating. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV. PMID:27116236

  7. Newcastle disease virus infection induces activation of the NLRP3 inflammasome.

    PubMed

    Wang, Binbin; Zhu, Jie; Li, Dandan; Wang, Yang; Zhan, Yuan; Tan, Lei; Qiu, Xusheng; Sun, Yingjie; Song, Cuiping; Meng, Chunchun; Ying, Liao; Xiang, Mao; Meng, Guangxun; Ding, Chan

    2016-09-01

    Inflammatory responses are important aspects of the innate immune system during virus infection. We found that Newcastle disease virus can induce inflammasome activation in the human macrophage-like cell line THP-1. Viral replication was required for inflammasome activation, and small hairpin RNA knockdown experiments indicated that IL-1β secretion was mediated by the NLRP3 inflammasome. We also verified the results in LPS-primed bone marrow-derived macrophages (BMDMs) from NLRP3-deficient and wild type mice. NDV is considered to be a promising oncolytic virus. Stimulating the immune system has been proposed as a key mechanism of oncolytic specificity, and the inflammasome appears to be an important mechanism by which NDV is controlled. Knockdown of inflammasome components or chemical inhibition of caspase-1 activity shows that cell survival was augmented and benefited NDV replication. This study shows that NLRP3 inflammasome activation is an innate cellular response to NDV infection and offers insights into the oncolytic specificity of NDV. PMID:27269659

  8. Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein

    PubMed Central

    Londono-Renteria, Berlin; Troupin, Andrea; Conway, Michael J; Vesely, Diana; Ledizet, Michael; Roundy, Christopher M.; Cloherty, Erin; Jameson, Samuel; Vanlandingham, Dana; Higgs, Stephen; Fikrig, Erol; Colpitts, Tonya M.

    2015-01-01

    Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious human disease and mortality worldwide. There is no specific antiviral therapy or vaccine for DENV infection. Alterations in gene expression during DENV infection of the mosquito and the impact of these changes on virus infection are important events to investigate in hopes of creating new treatments and vaccines. We previously identified 203 genes that were ≥5-fold differentially upregulated during flavivirus infection of the mosquito. Here, we examined the impact of silencing 100 of the most highly upregulated gene targets on DENV infection in its mosquito vector. We identified 20 genes that reduced DENV infection by at least 60% when silenced. We focused on one gene, a putative cysteine rich venom protein (SeqID AAEL000379; CRVP379), whose silencing significantly reduced DENV infection in Aedes aegypti cells. Here, we examine the requirement for CRVP379 during DENV infection of the mosquito and investigate the mechanisms surrounding this phenomenon. We also show that blocking CRVP379 protein with either RNAi or specific antisera inhibits DENV infection in Aedes aegypti. This work identifies a novel mosquito gene target for controlling DENV infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses. PMID:26491875

  9. Inhibition of Japanese encephalitis virus infection by the sulfated polysaccharide extracts from Ulva lactuca.

    PubMed

    Chiu, Ya-Huang; Chan, Yi-Lin; Li, Tsung-Lin; Wu, Chang-Jer

    2012-08-01

    Japanese encephalitis virus (JEV), a neurotropic flavivirus, is one of the major causes of acute encephalitis in humans. After infection, inflammatory reactions and neurological diseases often develop. Still there are no effective drugs available against virus infection. Recently, extracts of algae have been shown to possess a broad range of biological activities including antivirus activity. In this study, we identified that the sulfated polysaccharide extracts from Ulva lactuca can inhibit JEV infection in Vero cells. Mechanistic studies further revealed that the Ulva sulfated polysaccharide extracts can block virus adsorption and thus make the virus unable to enter cells. The Ulva sulfated polysaccharide extracts also effectively decrease the production of pro-inflammatory cytokines in the JEV-infected primary mixed glia cells. In an animal study, the JEV-infected C3H/HeN mice appeared to have neurobehavioral abnormalities on the fifth day and died on the seventh day post infection. However, the JEV-infected mice pretreated with the Ulva sulfated polysaccharide extracts can delay the onset of hind limb paralysis and thereby prevent mice from death. PMID:22193590

  10. Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection

    NASA Astrophysics Data System (ADS)

    Yin, Lu; Xu, Shuoyu; Cheng, Jierong; Zheng, Dahai; Limmon, Gino V.; Leung, Nicola H. N.; Rajapakse, Jagath C.; Chow, Vincent T. K.; Chen, Jianzhu; Yu, Hanry

    2013-04-01

    Lung injury caused by influenza virus infection is widespread. Understanding lung damage and repair progression post infection requires quantitative spatiotemporal information on various cell types mapping into the tissue structure. Based on high content images acquired from an automatic slide scanner, we have developed algorithms to quantify cell infiltration in the lung, loss and recovery of Clara cells in the damaged bronchioles and alveolar type II cells (AT2s) in the damaged alveolar areas, and induction of pro-surfactant protein C (pro-SPC)-expressing bronchiolar epithelial cells (SBECs). These quantitative analyses reveal: prolonged immune cell infiltration into the lung that persisted long after the influenza virus was cleared and paralleled with Clara cell recovery; more rapid loss and recovery of Clara cells as compared to AT2s; and two stages of SBECs from Scgb1a1+ to Scgb1a1-. These results provide evidence supporting a new mechanism of alveolar repair where Clara cells give rise to AT2s through the SBEC intermediates and shed light on the understanding of the lung damage and repair process. The approach and algorithms in quantifying cell-level changes in the tissue context (cell-based tissue informatics) to gain mechanistic insights into the damage and repair process can be expanded and adapted in studying other disease models.

  11. Autochthonous Hepatitis E Virus Infection in Europe: A Matter of Concern for Public Health?

    PubMed Central

    2014-01-01

    Human hepatitis E virus (HHEV) is the proposed name for a diverse group of RNA viruses from the family Hepeviridae that cause acute hepatitis among humans. Waterborne strains are regularly imported into Europe by international travelers, and virus transmission of zoonotic strains via contaminated aliments is involved in autochthonous cases. Therefore, in Europe, hepatitis E displays a unique dual character, having features of both imported and autochthonous infections. Environmental involvement of waterborne and zoonotic diseases puts alimentary safety at risk. In addition, it may lead to serious health problems derived from persistent infection among patients with immune impairment due to organ transplant, cancer, or human immunodeficiency virus infection. Although the European health authorities know at present that HHEV represents a problem worthy of consideration, the actual incidence of the disease in Europe is unknown, and attempts to ascertain the prevalence of the infection is hampered by unresolved technical issues. In order to determine the burden of hepatitis E in Europe, the World Health Organization Regional Office and the European Centre for Disease Prevention and Control should pay specific attention to hepatitis E, and research efforts in the continent should be transnational and collaborative. Development of a specific European network for hepatitis E would help to achieve these goals. PMID:26357613

  12. Development of a Hamster Model for Chikungunya Virus Infection and Pathogenesis

    PubMed Central

    Bosco-Lauth, Angela M.; Han, Sushan; Hartwig, Airn; Bowen, Richard A.

    2015-01-01

    Chikungunya virus is transmitted by mosquitoes and causes severe, debilitating infectious arthritis in humans. The need for an animal model to study the disease process and evaluate potential treatments is imminent as the virus continues its spread into novel geographic locations. Golden hamsters (Mesocricetus auratus) are often used as outbred laboratory animal models for arboviral diseases. Here we demonstrate that hamsters inoculated with chikungunya virus developed viremia and histopathologic lesions in their limbs and joints similar to those seen in human patients. The virus disseminated rapidly and was found in every major organ, including brain, within a few days of infection. Hamsters did not manifest overt clinical signs, and the virus was generally cleared within 4 days, followed by a strong neutralizing antibody response. These results indicate that hamsters are highly susceptible to chikungunya virus infection and develop myositis and tenosynovitis similar to human patients followed by a complete recovery. This animal model may be useful for testing antiviral drugs and vaccines. PMID:26070211

  13. Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection

    PubMed Central

    Liu, Kuan-Ting; Liu, Yao-Hua; Chen, Yen-Hsu; Lin, Chun-Yu; Huang, Chung-Hao; Yen, Meng-Chi; Kuo, Po-Lin

    2016-01-01

    Dengue fever is a serious threat for public health and induces various inflammatory cytokines and mediators, including galectins and glycoproteins. Diverse immune responses and immunological pathways are induced in different phases of dengue fever progression. However, the status of serum galectins and glycoproteins is not fully determined. The aim of this study was to investigate the serum concentration and potential interaction of soluble galectin-1, galectin-3, galectin-9, galectin-3 binding protein (galectin-3BP), glycoprotein 130 (gp130), and E-, L-, and P-selectin in patients with dengue fever in acute febrile phase. In this study, 317 febrile patients (187 dengue patients, 150 non-dengue patients that included 48 patients with bacterial infection and 102 patients with other febrile illness) who presented to the emergency department and 20 healthy controls were enrolled. Our results showed the levels of galectin-9 and galectin-3BP were significantly higher in dengue patients than those in healthy controls. Lower serum levels of galectin-1, galectin-3, and E-, L-, and P-selectin in dengue patients were detected compared to bacteria-infected patients, but not to healthy controls. In addition, strong correlation between galectin-9 and galectin-3BP was observed in dengue patients. In summary, our study suggested galectin-9 and galectin-3BP might be critical inflammatory mediators in acute dengue virus infection. PMID:27240351

  14. Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

    PubMed Central

    Vadlapudi, Aswani D.; Vadlapatla, Ramya K.; Mitra, Ashim K.

    2015-01-01

    Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections. PMID:23331181

  15. Zika Virus Infection and Stillbirths: A Case of Hydrops Fetalis, Hydranencephaly and Fetal Demise

    PubMed Central

    Sarno, Manoel; Sacramento, Gielson A.; Khouri, Ricardo; do Rosário, Mateus S.; Costa, Federico; Archanjo, Gracinda; Santos, Luciane A.; Nery, Nivison; Vasilakis, Nikos; Ko, Albert I.; de Almeida, Antonio R. P.

    2016-01-01

    Background The rapid spread of Zika virus in the Americas and current outbreak of microcephaly in Brazil has raised attention to the possible deleterious effects that the virus may have on fetuses. Methodology/Principal Findings We report a case of a 20-year-old pregnant woman who was referred to our service after a large Zika virus outbreak in the city of Salvador, Brazil with an ultrasound examination that showed intrauterine growth retardation of the fetus at the 18th gestational week. Ultrasound examinations in the 2nd and 3rd trimesters demonstrated severe microcephaly, hydranencephaly, intracranial calcifications and destructive lesions of posterior fossa, in addition to hydrothorax, ascites and subcutaneous edema. An induced labor was performed at the 32nd gestational week due to fetal demise and delivered a female fetus. ZIKV-specific real-time polymerase chain reaction amplification products were obtained from extracts of cerebral cortex, medulla oblongata and cerebrospinal and amniotic fluid, while extracts of heart, lung, liver, vitreous body of the eye and placenta did not yield detectable products. Conclusions/Significance This case report provides evidence that in addition to microcephaly, there may be a link between Zika virus infection and hydrops fetalis and fetal demise. Given the recent spread of the virus, systematic investigation of spontaneous abortions and stillbirths may be warranted to evaluate the risk that ZIKV infection imparts on these outcomes. PMID:26914330

  16. Virus enrichment for single virus infection by using 3D insulator based dielectrophoresis.

    PubMed

    Masuda, Taisuke; Maruyama, Hisataka; Honda, Ayae; Arai, Fumihito

    2014-01-01

    We developed an active virus filter (AVF) that enables virus enrichment for single virus infection, by using insulator-based dielectrophoresis (iDEP). A 3D-constricted flow channel design enabled the production of an iDEP force in the microfluidic chip. iDEP using a chip with multiple active virus filters (AVFs) was more accurate and faster than using a chip with a single AVF, and improved the efficiency of virus trapping. We utilized maskless photolithography to achieve the precise 3D gray-scale exposure required for fabrication of constricted flow channel. Influenza virus (A PR/8) was enriched by a negative DEP force when sinusoidal wave was applied to the electrodes within an amplitude range of 20 Vp-p and a frequency of 10 MHz. AVF-mediated virus enrichment can be repeated simply by turning the current ON or OFF. Furthermore, the negative AVF can inhibit virus adhesion onto the glass substrate. We then trapped and transported one of the enriched viruses by using optical tweezers. This microfluidic chip facilitated the effective transport of a single virus from AVFs towards the cell-containing chamber without crossing an electrode. We successfully transported the virus to the cell chamber (v = 10 µm/s) and brought it infected with a selected single H292 cell. PMID:24918921

  17. The antiviral activity of ribosomal polynucleotides against encephalomyocarditis virus infection of mice.

    PubMed

    Stewart, A G; Grantham, C A; Dawson, K M; Stebbing, N

    1980-01-01

    Intraperitoneal administration of ribosomal RNA (rRNA) was found to protect mice against subsequent lethal infection by encephalomyocarditis (EMC) virus without induction of detectable amounts of circulating interferon. The nature of this effect was examined in terms of the types of natural polyribonucleotides which could afford such protection. rRNA prepared from E. coli was slightly more effective than chicken liver rRNA which was, in turn, more effective than yeast rRNA. 5S ribosomal RNA was not effective, whereas the slightly smaller 4S transfer RNA was as good as E. coli rRNA, suggesting that molecular size is not the sole criterion for the protective effect. The separated 16S and 23S E. coli rRNAs where each as effective as the unfractionated RNA. Anti-viral activity was lost after complete hydrolysis with alkali and nucleoside monophosphates were also inactive. Digestion of rRNA with pancreatic ribonuclease greatly decreased its antiviral activity whereas digestion with T1 ribonuclease had no effect indicating that fairly short oligonucleotides, but not of random nucleotide sequence, are active components in the protection of mice against infection by EMC virus. In vitro, no antiviral effect against EMC virus infection was observed in treatment of L cells under various conditions. PMID:6160832

  18. Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection.

    PubMed

    Chan, Kuan Rong; Zhang, Summer Li-Xin; Tan, Hwee Cheng; Chan, Ying Kai; Chow, Angelia; Lim, Angeline Pei Chiew; Vasudevan, Subhash G; Hanson, Brendon J; Ooi, Eng Eong

    2011-07-26

    The interaction of antibodies, dengue virus (DENV), and monocytes can result in either immunity or enhanced virus infection. These opposing outcomes of dengue antibodies have hampered dengue vaccine development. Recent studies have shown that antibodies neutralize DENV by either preventing virus attachment to cellular receptors or inhibiting viral fusion intracellularly. However, whether the antibody blocks attachment or fusion, the resulting immune complexes are expected to be phagocytosed by Fc gamma receptor (FcγR)-bearing cells and cleared from circulation. This suggests that only antibodies that are able to block fusion intracellularly would be able to neutralize DENV upon FcγR-mediated uptake by monocytes whereas other antibodies would have resulted in enhancement of DENV replication. Using convalescent sera from dengue patients, we observed that neutralization of the homologous serotypes occurred despite FcγR-mediated uptake. However, FcγR-mediated uptake appeared to be inhibited when neutralized heterologous DENV serotypes were used instead. We demonstrate that this inhibition occurred through the formation of viral aggregates by antibodies in a concentration-dependent manner. Aggregation of viruses enabled antibodies to cross-link the inhibitory FcγRIIB, which is expressed at low levels but which inhibits FcγR-mediated phagocytosis and hence prevents antibody-dependent enhancement of DENV infection in monocytes. PMID:21746897

  19. Differentially expressed genes after viral haemorrhagic septicaemia virus infection in olive flounder (Paralichthys olivaceus).

    PubMed

    Hwang, Jee Youn; Kwon, Mun-Gyeong; Seo, Jung Soo; Do, Jung Wan; Park, Myoung-Ae; Jung, Sung-Hee; Ahn, Sang Jung

    2016-09-25

    A strain of viral haemorrhagic septicaemia virus (VHSV) was isolated from cultured olive flounder (Paralichthys olivaceus) during epizootics in South Korean. This strain showed high mortality to olive flounder in in vivo challenge experiment. The complete genomic RNA sequences were determined and phylogenetic analysis of the amino acid sequences of glycoprotein revealed that this isolate was grouped into genotype IVa of genus Novirhabdovirus. Expression profile of genes in olive flounder was analyzed at day 1 and day3 after infection with this VHSV isolate by using cDNA microarray containing olive flounder 13K cDNA clones. Microarray analysis revealed 785 up-regulated genes and 641 down-regulated genes by at least two-fold in virus-infected fish compared to healthy control groups. Among 785 up-regulated genes, we identified seven immune response-associated genes, including the interferon (IFN)-induced 56-kDa protein (IFI56), suppressor of cytokine signaling 1 (SOCS1), interleukin 8 (IL-8), cluster of differentiation 83 (CD83), α-globin (HBA), VHSV-induced protein-6 (VHSV6), and cluster of differentiation antigen 9 (CD9). Our results confirm previous reports that even virulent strain of VHSV induces expression of genes involved in protective immunity against VHSV. PMID:27599933

  20. Venezuelan equine encephalitis virus infection causes modulation of inflammatory and immune response genes in mouse brain

    PubMed Central

    Sharma, Anuj; Bhattacharya, Bhaskar; Puri, Raj K; Maheshwari, Radha K

    2008-01-01

    Background Neurovirulent Venezuelan equine encephalitis virus (VEEV) causes lethal encephalitis in equines and is transmitted to humans by mosquitoes. VEEV is highly infectious when transmitted by aerosol and has been developed as a bio-warfare agent, making it an important pathogen to study from a military and civilian standpoint. Molecular mechanisms of VEE pathogenesis are poorly understood. To study these, the gene expression profile of VEEV infected mouse brains was investigated. Changes in gene expression were correlated with histological changes in the brain. In addition, a molecular framework of changes in gene expression associated with progression of the disease was studied. Results Our results demonstrate that genes related to important immune pathways such as antigen presentation, inflammation, apoptosis and response to virus (Cxcl10, CxCl11, Ccl5, Ifr7, Ifi27 Oas1b, Fcerg1,Mif, Clusterin and MHC class II) were upregulated as a result of virus infection. The number of over-expressed genes (>1.5-fold level) increased as the disease progressed (from 197, 296, 400, to 1086 at 24, 48, 72 and 96 hours post infection, respectively). Conclusion Identification of differentially expressed genes in brain will help in the understanding of VEEV-induced pathogenesis and selection of biomarkers for diagnosis and targeted therapy of VEEV-induced neurodegeneration. PMID:18558011

  1. Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections

    PubMed Central

    Srivastava, Barkha; Błażejewska, Paulina; Heßmann, Manuela; Bruder, Dunja; Geffers, Robert; Mauel, Susanne; Gruber, Achim D.; Schughart, Klaus

    2009-01-01

    The genetic make-up of the host has a major influence on its response to combat pathogens. For influenza A virus, several single gene mutations have been described which contribute to survival, the immune response and clearance of the pathogen by the host organism. Here, we have studied the influence of the genetic background to influenza A H1N1 (PR8) and H7N7 (SC35M) viruses. The seven inbred laboratory strains of mice analyzed exhibited different weight loss kinetics and survival rates after infection with PR8. Two strains in particular, DBA/2J and A/J, showed very high susceptibility to viral infections compared to all other strains. The LD50 to the influenza virus PR8 in DBA/2J mice was more than 1000-fold lower than in C57BL/6J mice. High susceptibility in DBA/2J mice was also observed after infection with influenza strain SC35M. In addition, infected DBA/2J mice showed a higher viral load in their lungs, elevated expression of cytokines and chemokines, and a more severe and extended lung pathology compared to infected C57BL/6J mice. These findings indicate a major contribution of the genetic background of the host to influenza A virus infections. The overall response in highly susceptible DBA/2J mice resembled the pathology described for infections with the highly virulent influenza H1N1-1918 and newly emerged H5N1 viruses. PMID:19293935

  2. The Cationic Cytokine IL-26 Differentially Modulates Virus Infection in Culture

    PubMed Central

    Braum, Oliver; Klages, Michael; Fickenscher, Helmut

    2013-01-01

    Interleukin-26 (IL-26) belongs to the IL-10 cytokine family, is produced by activated T cells, and targets epithelial target cells for signal transduction. Here, we describe the IL-26 effects on the infection of culture cells with recombinant vesicular stomatitis virus (VSV), human cytomegalovirus (HCMV), and herpes simplex virus type 1 (HSV-1) expressing green fluorescent protein. After pre-incubation with recombinant IL-26 and at low multiplicity of infection, VSV showed strongly enhanced infection and replication rates as measured for infectivity, for transcript levels, and for protein expression. Control proteins did not affect VSV infection. The IL-26 effect was independent of the IL-26 receptor and neutralized by anti-IL-26 serum. Pre-incubation of VSV was much more efficient than pre-incubation of the target cells to enhance virus infection. IL-26 increased virus adsorption to target cells as shown by quantitative reverse-transcription PCR. In contrast, the infection of IL-26-treated human fibroblasts with HCMV was inhibited and the infection by HSV-1 was not altered by IL-26. Thus, IL-26 differentially modulates the infection by different enveloped viruses. PMID:23875025

  3. Poly(A) Polymerase from Vaccinia Virus-Infected Cells I. Partial Purification and Characterization

    PubMed Central

    Brakel, Christine; Kates, Joseph R.

    1974-01-01

    Poly(A) polymerase activity is induced during vaccinia virus infection of HeLa cells. The enzyme is maximally induced at 3.5 h postinfection. Partial purification frees the preparation of RNase activity and RNA polymerase activity. ATP is the substrate for poly(A) synthesis. A small amount of poly(A) is produced from added adenosine diphosphate due to the production of ATP by an adenylate kinase present in the preparation. The incorporation of ATP into poly(A) is dependent on divalent cations (Mg2+ or Mn2+) and is not inhibited by UTP, CTP, or GTP. Poly(U) stimulates ATP incorporation; poly(A) and poly(C) have little effect on ATP incorporation, and poly(dT) is extremely inhibitory. RNA prepared from HeLa cells and from the partially purified poly(A) polymerase (the enzyme preparation contains endogenous RNA [Brakel and Kates]) stimulates ATP incorporation by poly(A) polymerase which was subjected to DEAE-cellulose chromatography. RNase's, pancreatic and T1, inhibit the production of poly(A). DNase has little effect. Poly(U) is able to stimulate poly(A) production in the presence of T1 RNase. PMID:4417406

  4. The detection of hydrogen peroxide involved in plant virus infection by fluorescence spectroscopy.

    PubMed

    Lei, Rong; Du, Zhixin; Qiu, Yanhong; Zhu, Shuifang

    2016-08-01

    The production of reactive oxygen species (ROS) forms part of the defense reaction of plants against invading pathogens. ROS have multifaceted signaling functions in mediating the establishment of multiple responses. To verify whether hydrogen peroxide (H2 O2 ) contributes to plant virus infection and the development of induced symptoms, we used fluorescence to monitor the generation of H2 O2 and confocal laser scanning microscopy (CLSM) to investigate the subcellular distribution of H2 O2 in leaves. In this study, the M strain of Cucumber mosaic virus (M-CMV) induced heavy chlorotic symptoms in Nicotiana tabacum cv. white burley during systemic infection. Compared with mock-inoculated leaves, H2 O2 accumulation in inoculated leaves increased after inoculation, then decreased after 4 days. For systemically infected leaves that showed chlorotic symptoms, H2 O2 accumulation was always higher than in healthy leaves. Subcellular H2 O2 localization observed using CLSM showed that H2 O2 in inoculated leaves was generated mainly in the chloroplasts and cell wall, whereas in systemically infected leaves H2 O2 was generated mainly in the cytosol. The levels of coat protein in inoculated and systemically infected leaves might be associated with changes in the level of H2 O2 and symptom development. Further research is needed to elucidate the generation mechanism and the relationship between coat protein and oxidative stress during infection and symptom development. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27373455

  5. Transcriptional silencing of geminiviral promoter-driven transgenes following homologous virus infection.

    PubMed

    Seemanpillai, Mark; Dry, Ian; Randles, John; Rezaian, Ali

    2003-05-01

    Promoters isolated from the Tomato leaf curl virus (TLCV) drive both constitutive and tissue-specific expression in transgenic tobacco. Following systemic TLCV infection of plants stably expressing TLCV promoter:GUS transgenes, transgene expression driven by all six TLCV promoters was silenced. Silencing in the TLCV coat protein promoter:GUS plants (V2:GUSdeltaC) was characterized in more detail. Transgene silencing observed in leaf, stem, and pre-anthesis floral tissue occurred with the continued replication of TLCV in host tissues. Infection of the V2:GUSdeltaC plants with heterologous geminiviruses did not result in transgene silencing, indicating that silencing was specifically associated with TLCV infection. Nuclear run-on assays indicated that silencing was due to the abolition of transcription from the V2:GUSdeltaC transgene. Bisulfite sequencing showed that silencing was associated with cytosine hypermethylation of the TLCV-derived promoter sequences of the V2:GUSdeltaC transgene. Progeny derived from V2:GUSdeltaC plants silenced by TLCV infection were analyzed. Transgene expression was silenced in progeny seedlings but was partially reactivated in the majority of plants by 75 days postgermination. Progeny seedlings treated with the nonmethylatable cytosine analog 5-azacytidine or the histone deacetylase inhibitor sodium butyrate exhibited partial reactivation of expression. This is the first report of the hypermethylation of a virus-derived transgene associated with a DNA virus infection. PMID:12744514

  6. Regulation of influenza virus infection by long non-coding RNAs.

    PubMed

    Landeras-Bueno, Sara; Ortín, Juan

    2016-01-01

    Influenza A viruses generate annual epidemics and occasional pandemics of respiratory disease with important consequences for human health and economy. To establish a productive infection, influenza viruses interact with cellular factors to favour their own replication and to suppress antiviral cell responses. Although most virus-host interaction studies have been centred on cell protein factors, most of the human transcriptome comprises non-coding RNAs, as miRNAs and lncRNAs. The latter are key cellular regulators in many cellular processes, including transcriptional and post-transcriptional regulation. Influenza virus infection induces the differential expression of hundreds of potential lncRNAs, some of which are related to the antiviral pathways activated by the cell while others may be deregulated by the infection to allow efficient virus multiplication. Although our knowledge on the role of cellular lncRNAs for influenza virus replication and pathogenesis is still at its infancy, several lncRNAs have been described to influence the cell innate response to the virus by altering the histone modification at specific sites, by interaction with specific transcription factors or directly stimulating in cis the expression of specific IFN-induced genes. In addition, at least one lncRNA appears to be required for virus multiplication in an IFN-independent way. PMID:26321158

  7. ELEVATED LEVELS OF SOLUBLE ST2 PROTEIN IN DENGUE VIRUS INFECTED PATIENTS

    PubMed Central

    Becerra, Aniuska; Warke, Rajas V.; de Bosch, Norma; Rothman, Alan L.; Bosch, Irene

    2008-01-01

    Levels of the soluble form of the interleukin-1 receptor like 1 protein (IL-1RL-1 / ST2) are elevated in the serum of patients with diseases characterized by an inflammatory response. The objective of this study was to determine the concentration of soluble ST2 (sST2) in dengue infected patients during the course of the disease. Twenty four patients with confirmed dengue infection, classified as dengue fever, and eleven patients with other febrile illness (OFI) were evaluated. Levels of sST2 in serum and laboratory variables usually altered during dengue infections were measured. Dengue infected patients had higher serum sST2 levels than OFI at the end of the febrile stage and at defervescence (p=0.0088 and p=0.0004 respectively). Patients with secondary dengue infections had higher serum sST2 levels compared with patients with primary dengue infections (p=0.047 at last day of fever and p=0.030 at defervescence). Furthermore, in dengue infected patients, we found a significant negative correlation of sST2 with platelet and WBC counts, and positive correlation with thrombin time and transaminases activity. We suggest that sST2 could be a potential marker of dengue infection, could be associated with severity or could play a role in the immune response in secondary dengue virus infection. PMID:18226917

  8. Considerations in the Use of Nonhuman Primate Models of Ebola Virus and Marburg Virus Infection.

    PubMed

    Geisbert, Thomas W; Strong, James E; Feldmann, Heinz

    2015-10-01

    The filoviruses, Ebola virus and Marburg virus, are zoonotic pathogens that cause severe hemorrhagic fever in humans and nonhuman primates (NHPs), with case-fatality rates ranging from 23% to 90%. The current outbreak of Ebola virus infection in West Africa, with >26 000 cases, demonstrates the long-underestimated public health danger that filoviruses pose as natural human pathogens. Currently, there are no vaccines or treatments licensed for human use. Licensure of any medical countermeasure may require demonstration of efficacy in the gold standard cynomolgus or rhesus macaque models of filovirus infection. Substantial progress has been made over the last decade in characterizing the filovirus NHP models. However, there is considerable debate over a variety of experimental conditions, including differences among filovirus isolates used, routes and doses of exposure, and euthanasia criteria, all of which may contribute to variability of results among different laboratories. As an example of the importance of understanding these differences, recent data with Ebola virus shows that an addition of a single uridine residue in the glycoprotein gene at the editing site attenuates the virus. Here, we draw on decades of experience working with filovirus-infected NHPs to provide a perspective on the importance of various experimental conditions. PMID:26063223

  9. Prophylactic Efficacy of Quercetin 3-β-O-d-Glucoside against Ebola Virus Infection.

    PubMed

    Qiu, Xiangguo; Kroeker, Andrea; He, Shihua; Kozak, Robert; Audet, Jonathan; Mbikay, Majambu; Chrétien, Michel

    2016-09-01

    Ebola outbreaks occur on a frequent basis, with the 2014-2015 outbreak in West Africa being the largest one ever recorded. This outbreak has resulted in over 11,000 deaths in four African countries and has received international attention and intervention. Although there are currently no approved therapies or vaccines, many promising candidates are undergoing clinical trials, and several have had success in promoting recovery from Ebola. However, these prophylactics and therapeutics have been designed and tested only against the same species of Ebola virus as the one causing the current outbreak. Future outbreaks involving other species would require reformulation and possibly redevelopment. Therefore, a broad-spectrum alternative is highly desirable. We have found that a flavonoid derivative called quercetin 3-β-O-d-glucoside (Q3G) has the ability to protect mice from Ebola even when given as little as 30 min prior to infection. Furthermore, we have demonstrated that this compound targets the early steps of viral entry. Most promisingly, antiviral activity against two distinct species of Ebola virus was seen. This study serves as a proof of principle that Q3G has potential as a prophylactic against Ebola virus infection. PMID:27297486

  10. Parainfluenza virus infection associated with posterior reversible encephalopathy syndrome: a case report

    PubMed Central

    2012-01-01

    Introduction Posterior reversible encephalopathy syndrome is a clinical and radiological entity. The most accepted theory of posterior reversible encephalopathy syndrome is a loss of autoregulation in cerebral blood flow with a subsequent increase in vascular permeability and leakage of blood plasma and erythrocytes, producing vasogenic edema. In infection-associated posterior reversible encephalopathy syndrome, a clinical pattern consistent with systemic inflammatory response syndrome develops. Parainfluenza virus has not been reported in the medical literature to be associated with posterior reversible encephalopathy syndrome. Case presentation We report herein the case of a 54-year-old Caucasian woman with posterior reversible encephalopathy syndrome associated with parainfluenza virus infection who presented with generalized headache, blurring of vision, new-onset seizure and flu-like symptoms. Conclusion Infection-associated posterior reversible encephalopathy syndrome as well as hypertension-associated posterior reversible encephalopathy syndrome favor the contribution of endothelial dysfunction to the pathophysiology of this clinicoradiological syndrome. In view of the reversible nature of this clinical entity, it is important that all physicians are well aware of posterior reversible encephalopathy syndrome in patients presenting with headache and seizure activity. A detailed clinical assessment leading to the recognition of precipitant factors in posterior reversible encephalopathy syndrome is paramount. PMID:22448715

  11. Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection.

    PubMed

    Liu, Kuan-Ting; Liu, Yao-Hua; Chen, Yen-Hsu; Lin, Chun-Yu; Huang, Chung-Hao; Yen, Meng-Chi; Kuo, Po-Lin

    2016-01-01

    Dengue fever is a serious threat for public health and induces various inflammatory cytokines and mediators, including galectins and glycoproteins. Diverse immune responses and immunological pathways are induced in different phases of dengue fever progression. However, the status of serum galectins and glycoproteins is not fully determined. The aim of this study was to investigate the serum concentration and potential interaction of soluble galectin-1, galectin-3, galectin-9, galectin-3 binding protein (galectin-3BP), glycoprotein 130 (gp130), and E-, L-, and P-selectin in patients with dengue fever in acute febrile phase. In this study, 317 febrile patients (187 dengue patients, 150 non-dengue patients that included 48 patients with bacterial infection and 102 patients with other febrile illness) who presented to the emergency department and 20 healthy controls were enrolled. Our results showed the levels of galectin-9 and galectin-3BP were significantly higher in dengue patients than those in healthy controls. Lower serum levels of galectin-1, galectin-3, and E-, L-, and P-selectin in dengue patients were detected compared to bacteria-infected patients, but not to healthy controls. In addition, strong correlation between galectin-9 and galectin-3BP was observed in dengue patients. In summary, our study suggested galectin-9 and galectin-3BP might be critical inflammatory mediators in acute dengue virus infection. PMID:27240351

  12. A rabbit model for mucosal immunity in the bowel. II. Local cellular reactivity to virus infection.

    PubMed Central

    Ramsay, A J; Holmes, M J

    1990-01-01

    An animal model was used to examine local and systemic cellular reactivity against virus infection of bowel mucosa. Firstly, existing techniques for extracting lymphoid cells from the dispersed populations of the bowel mucosa were adapted for use in rabbits and viable lymphocytes were isolated from the lapine ileal mucosa in numbers suitable for assay. Lamina propria lymphocytes (LPL) showed a strong blastogenic response to T-cell mitogens but intra-epithelial lymphocytes (IEL) responded poorly, even in the presence of splenic accessory cells. Next, chronically isolated ileal loops in rabbits were infected with parainfluenzavirus type 3 (PI-3) and isolates from the organized and dispersed lymphoid tissues associated with infected ileal mucosae and those from systemic lymphoid sites were used in in vitro assays of virus-specific lympho-proliferation. A T-cell-mediated immune response against PI-3 was mounted in lymphoid tissues associated with the infected loops, appearing first in loop Peyer's patches (PP) at Day 4 and in mesenteric lymph nodes (MLN) and lamina propriae at Day 7 after infection. The response in PP had waned by 21 days but was sustained in the other sites for at least 42 days. Epithelial lymphocytes were consistently anergic and there was no evidence of specific reactivity at systemic lymphoid sites or elsewhere in the bowel. Thus, a highly localized T-cell-mediated response was sustained, not only in organized lymphoid tissues but also in the bowel wall itself, following infection with a novel antigen. PMID:2155872

  13. Host Responses in Life-History Traits and Tolerance to Virus Infection in Arabidopsis thaliana

    PubMed Central

    Pagán, Israel; Alonso-Blanco, Carlos; García-Arenal, Fernando

    2008-01-01

    Knowing how hosts respond to parasite infection is paramount in understanding the effects of parasites on host populations and hence host–parasite co-evolution. Modification of life-history traits in response to parasitism has received less attention than other defence strategies. Life-history theory predicts that parasitised hosts will increase reproductive effort and accelerate reproduction. However, empirical analyses of these predictions are few and mostly limited to animal-parasite systems. We have analysed life-history trait responses in 18 accessions of Arabidopsis thaliana infected at two different developmental stages with three strains of Cucumber mosaic virus (CMV). Accessions were divided into two groups according to allometric relationships; these groups differed also in their tolerance to CMV infection. Life-history trait modification upon virus infection depended on the host genotype and the stage at infection. While all accessions delayed flowering, only the more tolerant allometric group modified resource allocation to increase the production of reproductive structures and progeny, and reduced the length of reproductive period. Our results are in agreement with modifications of life-history traits reported for parasitised animals and with predictions from life-history theory. Thus, we provide empirical support for the general validity of theoretical predictions. In addition, this experimental approach allowed us to quantitatively estimate the genetic determinism of life-history trait plasticity and to evaluate the role of life-history trait modification in defence against parasites, two largely unexplored issues. PMID:18704166

  14. [Hepatitis A virus infection in Amerindian area in the east Brazilian Amazon].

    PubMed

    Nunes, Heloisa Marceliano; Soares, Manoel do Carmo Pereira; Silva, Helena Maria Ribeiro

    2004-01-01

    The hepatitis A virus infection represents an important problem of public health all over the world, being related to the socioeconomic and hygienic conditions of the population. In Brazilian Amazon, seroepidemiological studies in amerindians populations have been demonstrating high endemicity related to the infection. With the objective of evaluate the prevalence of the hepatitis virus A infection in xicrin village, in the municipality district of Altamira-Pará-Brazil, whose investigation was unchained by indigenous child's obit, that clinical developed in nine days with a picture icterus-hemorrhagic, without confirmation by serologic exams, 352 samples of blood were analyzed by serologic tests of the markers of the hepatitis A, B, C and D virus, for immunoenzymatic technic, that indicated a prevalence of 98% of antibodies against the hepatitis A virus, which 30.5% with recent infection, characterizing in laboratorial basis, the outbreak of infection for the virus of the hepatitis A and raising the possibility to be associated with the obit happened in the village. PMID:15586897

  15. Inhibition of the Type I Interferon Response by the Nucleoprotein of the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus

    PubMed Central

    Martínez-Sobrido, Luis; Zúñiga, Elina I.; Rosario, Debralee; García-Sastre, Adolfo; de la Torre, Juan Carlos

    2006-01-01

    The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a formidable battle horse for the study of viral immunology, as well as viral persistence and associated diseases. Investigations with LCMV have uncovered basic mechanisms by which viruses avoid elimination by the host adaptive immune response. In this study we show that LCMV also disables the host innate defense by interfering with beta interferon (IFN-β) production in response to different stimuli, including infection with Sendai virus and liposome-mediated DNA transfection. Inhibition of IFN production in LCMV-infected cells was caused by an early block in the IFN regulatory factor 3 (IRF-3) activation pathway. This defect was restored in cells cured of LCMV, indicating that one or more LCMV products are responsible for the inhibition of IRF-3 activation. Using expression plasmids encoding individual LCMV proteins, we found that expression of the LCMV nucleoprotein (NP) was sufficient to inhibit both IFN production and nuclear translocation of IRF-3. To our knowledge, this is the first evidence of an IFN-counteracting viral protein in the Arenaviridae family. Inhibition of IFN production by the arenavirus NP is likely to be a determinant of virulence in vivo. PMID:16940530

  16. Virus Infection of Plants Alters Pollinator Preference: A Payback for Susceptible Hosts?

    PubMed Central

    Davey, Matthew P.; Bruce, Toby J. A.; Caulfield, John C.; Furzer, Oliver J.; Reed, Alison; Robinson, Sophie I.; Miller, Elizabeth; Davis, Christopher N.; Pickett, John A.; Whitney, Heather M.; Glover, Beverley J.; Carr, John P.

    2016-01-01

    Plant volatiles play important roles in attraction of certain pollinators and in host location by herbivorous insects. Virus infection induces changes in plant volatile emission profiles, and this can make plants more attractive to insect herbivores, such as aphids, that act as viral vectors. However, it is unknown if virus-induced alterations in volatile production affect plant-pollinator interactions. We found that volatiles emitted by cucumber mosaic virus (CMV)-infected tomato (Solanum lycopersicum) and Arabidopsis thaliana plants altered the foraging behaviour of bumblebees (Bombus terrestris). Virus-induced quantitative and qualitative changes in blends of volatile organic compounds emitted by tomato plants were identified by gas chromatography-coupled mass spectrometry. Experiments with a CMV mutant unable to express the 2b RNA silencing suppressor protein and with Arabidopsis silencing mutants implicate microRNAs in regulating emission of pollinator-perceivable volatiles. In tomato, CMV infection made plants emit volatiles attractive to bumblebees. Bumblebees pollinate tomato by ‘buzzing’ (sonicating) the flowers, which releases pollen and enhances self-fertilization and seed production as well as pollen export. Without buzz-pollination, CMV infection decreased seed yield, but when flowers of mock-inoculated and CMV-infected plants were buzz-pollinated, the increased seed yield for CMV-infected plants was similar to that for mock-inoculated plants. Increased pollinator preference can potentially increase plant reproductive success in two ways: i) as female parents, by increasing the probability that ovules are fertilized; ii) as male parents, by increasing pollen export. Mathematical modeling suggested that over a wide range of conditions in the wild, these increases to the number of offspring of infected susceptible plants resulting from increased pollinator preference could outweigh underlying strong selection pressures favoring pathogen resistance

  17. Successful Interferon-Free Therapy of Chronic Hepatitis C Virus Infection Normalizes Natural Killer Cell Function

    PubMed Central

    Serti, Elisavet; Chepa-Lotrea, Xenia; Kim, Yun Ju; Keane, Meghan; Fryzek, Nancy; Liang, T. Jake; Ghany, Marc; Rehermann, Barbara

    2015-01-01

    BACKGROUND & AIMS Chronic hepatitis C virus infection activates an intrahepatic immune response, leading to increased expression of interferon (IFN)-stimulated genes and activation of natural killer (NK) cells—the most prevalent innate immune cell in the liver. We investigated whether the elimination of HCV with direct-acting antiviral agents normalizes expression of IFN-stimulated genes and NK cell function. METHODS We used multicolor flow cytometry to analyze NK cells from liver and blood of 13 HCV-infected patients who did not respond to treatment with pegylated interferon and ribavirin. Samples were collected before and during IFN-free treatment with daclatasvir and asunaprevir therapy and compared with those from blood of 13 healthy individuals (controls). Serum levels of CXCL10 and CXCL11 were measured by ELISA. RESULTS Before treatment, all patients had increased levels of CXCL10 or CXCL11 and a different NK cell phenotype from controls, characterized by increased expression of HLA-DR, NKp46, NKG2A, CD85j, pSTAT1, STAT1, and TNF-related apoptosis-inducing ligand (TRAIL). NK cells from patients also had increased degranulation and decreased production of IFNγ and TNFα compared with NK cells from controls. Nine patients had an end-of-treatment response (undetectable virus) and 4 had virologic breakthrough between weeks 4 and 12 of therapy. A rapid decrease in viremia and level of inflammatory cytokines in all patients was associated with decreased activation of intrahepatic and blood NK cells; it was followed by restoration of a normal NK cell phenotype and function by week 8 in patients with undetectable viremia. This normalized NK cell phenotype was maintained until week 24 (EOT). CONCLUSIONS DAA-mediated clearance of HCV is associated with loss of intrahepatic immune activation by IFNα, indicated by decreased levels of CXCL10 and CXCL11 and normalization of NK cell phenotype and function. PMID:25754160

  18. Ecological Dynamics of Two Distinct Viruses Infecting Marine Eukaryotic Decomposer Thraustochytrids (Labyrinthulomycetes, Stramenopiles).

    PubMed

    Takao, Yoshitake; Tomaru, Yuji; Nagasaki, Keizo; Honda, Daiske

    2015-01-01

    Thraustochytrids are cosmopolitan osmotrophic or heterotrophic microorganisms that are considered as important decomposers in coastal ecosystems. However, because of a lack of estimation method for each genus or systematic group of them, relatively little is known about their ecology in situ. Previously, we reported two distinct types of virus infecting thraustochytrids (AuRNAV: reported as SssRNAV, and SmDNAV) suggesting they have wide distributions in the host-virus systems of coastal environments. Here we conducted a field survey from 2004 through 2005 to show the fluctuation pattern of thraustochytrids and their viruses in Hiroshima Bay, Japan. During the field survey, we monitored the dynamics of the two types of thraustochytrid-infecting virus: small viruses causing lysis of Aurantiochytrium sp. NIBH N1-27 (identified as AuRNAV) and the large viruses of Sicyoidochytrium minutum NBRC 102975 (similar to SmDNAV in physiology and morphology). Fluctuation patterns of the two distinct types of virus were different from each other. This may reflect the difference in the preference of organic substrates; i.e., it may be likely the host of AuRNAV (Aurantiochytrium sp.) increases utilizing algal dead bodies or feeble cells as the virus shows a large increase in abundance following raphidophyte blooms; whereas, the trophic nutrient supply for S. minutum may primarily depend on other constantly-supplied organic compounds because it did not show any significant change in abundance throughout the survey. Further study concerning the population composition of thraustochytrids and their viruses may demonstrate the microbial ecology (especially concerning the detrital food web) of marine environments. PMID:26203654

  19. Ecological Dynamics of Two Distinct Viruses Infecting Marine Eukaryotic Decomposer Thraustochytrids (Labyrinthulomycetes, Stramenopiles)

    PubMed Central

    Takao, Yoshitake; Tomaru, Yuji; Nagasaki, Keizo; Honda, Daiske

    2015-01-01

    Thraustochytrids are cosmopolitan osmotrophic or heterotrophic microorganisms that are considered as important decomposers in coastal ecosystems. However, because of a lack of estimation method for each genus or systematic group of them, relatively little is known about their ecology in situ. Previously, we reported two distinct types of virus infecting thraustochytrids (AuRNAV: reported as SssRNAV, and SmDNAV) suggesting they have wide distributions in the host-virus systems of coastal environments. Here we conducted a field survey from 2004 through 2005 to show the fluctuation pattern of thraustochytrids and their viruses in Hiroshima Bay, Japan. During the field survey, we monitored the dynamics of the two types of thraustochytrid-infecting virus: small viruses causing lysis of Aurantiochytrium sp. NIBH N1-27 (identified as AuRNAV) and the large viruses of Sicyoidochytrium minutum NBRC 102975 (similar to SmDNAV in physiology and morphology). Fluctuation patterns of the two distinct types of virus were different from each other. This may reflect the difference in the preference of organic substrates; i.e., it may be likely the host of AuRNAV (Aurantiochytrium sp.) increases utilizing algal dead bodies or feeble cells as the virus shows a large increase in abundance following raphidophyte blooms; whereas, the trophic nutrient supply for S. minutum may primarily depend on other constantly-supplied organic compounds because it did not show any significant change in abundance throughout the survey. Further study concerning the population composition of thraustochytrids and their viruses may demonstrate the microbial ecology (especially concerning the detrital food web) of marine environments. PMID:26203654

  20. The Enterovirus 71 Procapsid Binds Neutralizing Antibodies and Rescues Virus Infection In Vitro

    PubMed Central

    Shingler, Kristin L.; Cifuente, Javier O.; Ashley, Robert E.; Makhov, Alexander M.; Conway, James F.

    2014-01-01

    ABSTRACT Enterovirus 71 (EV71) is responsible for seasonal outbreaks of hand, foot, and mouth disease in the Asia-Pacific region. The virus has the capability to cause severe disease and death, especially in young children. Although several vaccines are currently in clinical trials, no vaccines or therapeutics have been approved for use. Previous structural studies have revealed that two antigenically distinct capsid forms are produced in EV71-infected cells: an expanded empty capsid, sometimes called a procapsid, and the infectious virus. Specifically, an immunodominant epitope of EV71 that maps to the virus canyon is structurally different in the procapsid and virus. This structure-function study shows that the procapsid can sequester antibodies, thus enhancing EV71 infection in vitro. The results presented here suggest that, due to conformational differences between the EV71 procapsid and virus, the presence of the procapsid in natural virus infections should be considered in the future design of vaccines or therapeutics. IMPORTANCE In a picornavirus infection, both an infectious and a noninfectious empty capsid, sometimes referred to as a procapsid, are produced. It was novel to discover that the procapsid form of EV71 was expanded and antigenically distinct from the infectious virus. Previously, it had been supposed that this empty capsid was an off-pathway dead end or at best served for storage of pentameric subunits, which was later shown to be unlikely. It remains unexplained why picornaviruses evolutionarily conserve the wasteful production of so much noninfectious capsid. Here, we demonstrate that the EV71 procapsid has different antigenic properties than the infectious virus. Thus, the procapsid has the capacity to sequester neutralizing antibody and protect the virus, promoting or restoring a successful infection in vitro. This important observation should be considered in the future design and development of vaccines and therapeutics. PMID:25428877

  1. Inhibition of hepatitis C virus infection by DNA aptamer against envelope protein.

    PubMed

    Yang, Darong; Meng, Xianghe; Yu, Qinqin; Xu, Li; Long, Ying; Liu, Bin; Fang, Xiaohong; Zhu, Haizhen

    2013-10-01

    Hepatitis C virus (HCV) envelope protein (E1E2) is essential for virus binding to host cells. Aptamers have been demonstrated to have strong promising applications in drug development. In the current study, a cDNA fragment encoding the entire E1E2 gene of HCV was cloned. E1E2 protein was expressed and purified. Aptamers for E1E2 were selected by the method of selective evolution of ligands by exponential enrichment (SELEX), and the antiviral actions of the aptamers were examined. The mechanism of their antiviral activity was investigated. The data show that selected aptamers for E1E2 specifically recognize the recombinant E1E2 protein and E1E2 protein from HCV-infected cells. CD81 protein blocks the binding of aptamer E1E2-6 to E1E2 protein. Aptamers against E1E2 inhibit HCV infection in an infectious cell culture system although they have no effect on HCV replication in a replicon cell line. Beta interferon (IFN-β) and IFN-stimulated genes (ISGs) are not induced in virus-infected hepatocytes with aptamer treatment, suggesting that E1E2-specific aptamers do not induce innate immunity. E2 protein is essential for the inhibition of HCV infection by aptamer E1E2-6, and the aptamer binding sites are located in E2. Q412R within E1E2 is the major resistance substitution identified. The data indicate that an aptamer against E1E2 exerts its antiviral effects through inhibition of virus binding to host cells. Aptamers against E1E2 can be used with envelope protein to understand the mechanisms of HCV entry and fusion. The aptamers may hold promise for development as therapeutic drugs for hepatitis C patients. PMID:23877701

  2. Zika virus infection during pregnancy and microcephaly occurrence: a review of literature and Brazilian data.

    PubMed

    De Carvalho, Newton Sérgio; De Carvalho, Beatriz Freitas; Fugaça, Cyllian Arias; Dóris, Bruna; Biscaia, Evellyn Silverio

    2016-01-01

    In November of 2015, the Ministry of Health of Brazil published an announcement confirming the relationship between Zika virus and the microcephaly outbreak in the Northeast, suggesting that infected pregnant women might have transmitted the virus to their fetuses. The objectives of this study were to conduct a literature review about Zika virus infection and microcephaly, evaluate national and international epidemiological data, as well as the current recommendations for the health teams. Zika virus is an arbovirus, whose main vector is the Aedes sp. The main symptoms of the infection are maculopapular rash, fever, non-purulent conjunctivitis, and arthralgia. Transmission of this pathogen occurs mainly by mosquito bite, but there are also reports via the placenta. Microcephaly is defined as a measure of occipto-frontal circumference being more than two standard deviations below the mean for age and gender. The presence of microcephaly demands evaluation of the patient, in order to diagnose the etiology. Health authorities issued protocols, reports and notes concerning the management of microcephaly caused by Zika virus, but there is still controversy about managing the cases. The Ministry of Health advises notifying any suspected or confirmed cases of children with microcephaly related to the pathogen, which is confirmed by a positive specific laboratory test for the virus. The first choice for imaging exam in children with this malformation is transfontanellar ultrasound. The most effective way to control this outbreak of microcephaly probably caused by this virus is to combat the vector. Since there is still uncertainty about the period of vulnerability of transmission via placenta, the use of repellents is crucial throughout pregnancy. More investigations studying the consequences of this viral infection on the body of newborns and in their development are required. PMID:27102780

  3. Virus Infection of Plants Alters Pollinator Preference: A Payback for Susceptible Hosts?

    PubMed

    Groen, Simon C; Jiang, Sanjie; Murphy, Alex M; Cunniffe, Nik J; Westwood, Jack H; Davey, Matthew P; Bruce, Toby J A; Caulfield, John C; Furzer, Oliver J; Reed, Alison; Robinson, Sophie I; Miller, Elizabeth; Davis, Christopher N; Pickett, John A; Whitney, Heather M; Glover, Beverley J; Carr, John P

    2016-08-01

    Plant volatiles play important roles in attraction of certain pollinators and in host location by herbivorous insects. Virus infection induces changes in plant volatile emission profiles, and this can make plants more attractive to insect herbivores, such as aphids, that act as viral vectors. However, it is unknown if virus-induced alterations in volatile production affect plant-pollinator interactions. We found that volatiles emitted by cucumber mosaic virus (CMV)-infected tomato (Solanum lycopersicum) and Arabidopsis thaliana plants altered the foraging behaviour of bumblebees (Bombus terrestris). Virus-induced quantitative and qualitative changes in blends of volatile organic compounds emitted by tomato plants were identified by gas chromatography-coupled mass spectrometry. Experiments with a CMV mutant unable to express the 2b RNA silencing suppressor protein and with Arabidopsis silencing mutants implicate microRNAs in regulating emission of pollinator-perceivable volatiles. In tomato, CMV infection made plants emit volatiles attractive to bumblebees. Bumblebees pollinate tomato by 'buzzing' (sonicating) the flowers, which releases pollen and enhances self-fertilization and seed production as well as pollen export. Without buzz-pollination, CMV infection decreased seed yield, but when flowers of mock-inoculated and CMV-infected plants were buzz-pollinated, the increased seed yield for CMV-infected plants was similar to that for mock-inoculated plants. Increased pollinator preference can potentially increase plant reproductive success in two ways: i) as female parents, by increasing the probability that ovules are fertilized; ii) as male parents, by increasing pollen export. Mathematical modeling suggested that over a wide range of conditions in the wild, these increases to the number of offspring of infected susceptible plants resulting from increased pollinator preference could outweigh underlying strong selection pressures favoring pathogen resistance

  4. Multiple regulatory domains control IRF-7 activity in response to virus infection.

    PubMed

    Lin, R; Mamane, Y; Hiscott, J

    2000-11-01

    Recent studies implicate the interferon regulatory factors (IRF), IRF-3 and IRF-7, as key activators of Type 1 interferon genes, as well as the RANTES (regulated on activation normal T cell expressed) chemokine gene. Both IRF-3 and IRF-7 are regulated in part by virus-induced C-terminal phosphorylation, leading to nuclear translocation, stimulation of DNA binding, and transcriptional activities. Structure-function studies with IRF-7 suggested a complex organization of the C-terminal region, with a constitutive activation domain located between amino acids 150-246, an accessory inducibility region at the very end of IRF-7 between amino acids 467 and 503, and an inhibitory region (amino acids 341-467) adjacent to the C-terminal end that interferes with transactivation. Furthermore, an element that increases basal and virus-inducible activity is located between amino acids 278 and 305. A transcriptionally active form of IRF-7 was also generated by substitution of Ser-477 and Ser-479 residues with the phosphomimetic Asp. IRF-7, particularly IRF-7(S477D/S479D), was a strong transactivator of type I interferon and RANTES chemokine gene expression. Unlike wild type IRF-3, IRF-7 overexpression was able to stimulate inteferon gene expression in the absence of virus infection. Using tagged versions of IRF-7 and IRF-3, the formation of homo- and heterodimers was detected by co-immunoprecipitation. These results demonstrate that IRF-3 and IRF-7 transcription factors possess distinct structural characteristics that impart complementary rather than redundant functional roles in cytokine gene activation. PMID:10893229

  5. Plant Growth Retardation and Conserved miRNAs Are Correlated to Hibiscus Chlorotic Ringspot Virus Infection

    PubMed Central

    Gao, Ruimin; Wan, Zi Yi; Wong, Sek-Man

    2013-01-01

    Virus infection may cause a multiplicity of symptoms in their host including discoloration, distortion and growth retardation. Hibiscus chlorotic ringspot virus (HCRSV) infection was studied using kenaf (Hibiscus cannabinus L.), a non-wood fiber-producing crop in this study. Infection by HCRSV reduced the fiber yield and concomitant economic value of kenaf. We investigated kenaf growth retardation and fluctuations of four selected miRNAs after HCRSV infection. Vegetative growth (including plant height, leaf size and root development) was severely retarded. From the transverse and radial sections of the mock and HCRSV-infected kenaf stem, the vascular bundles of HCRSV-infected plants were severely disrupted. In addition, four conserved plant developmental and defence related microRNAs (miRNAs) (miR165, miR167, miR168 and miR171) and their respective target genes phabulosa (PHB), auxin response factor 8 (ARF8), argonaute 1 (AGO1) and scarecrow-like protein 1 (SCL1) displayed variation in expression levels after HCRSV infection. Compared with the mock inoculated kenaf plants, miR171 and miR168 and their targets SCL1 and AGO1 showed greater fluctuations after HCRSV infection. As HCRSV upregulates plant SO transcript in kenaf and upregulated AGO1 in HCRSV-infected plants, the expression level of AGO1 transcript was further investigated under sulfite oxidase (SO) overexpression or silencing condition. Interestingly, the four selected miRNAs were also up- or down-regulated upon overexpression or silencing of SO. Plant growth retardation and fluctuation of four conserved miRNAs are correlated to HCRSV infection. PMID:24386476

  6. Model-based projections of Zika virus infections in childbearing women in the Americas.

    PubMed

    Alex Perkins, T; Siraj, Amir S; Ruktanonchai, Corrine W; Kraemer, Moritz U G; Tatem, Andrew J

    2016-01-01

    Zika virus is a mosquito-borne pathogen that is rapidly spreading across the Americas. Due to associations between Zika virus infection and a range of fetal maladies(1,2), the epidemic trajectory of this viral infection poses a significant concern for the nearly 15 million children born in the Americas each year. Ascertaining the portion of this population that is truly at risk is an important priority. One recent estimate(3) suggested that 5.42 million childbearing women live in areas of the Americas that are suitable for Zika occurrence. To improve on that estimate, which did not take into account the protective effects of herd immunity, we developed a new approach that combines classic results from epidemiological theory with seroprevalence data and highly spatially resolved data about drivers of transmission to make location-specific projections of epidemic attack rates. Our results suggest that 1.65 (1.45-2.06) million childbearing women and 93.4 (81.6-117.1) million people in total could become infected before the first wave of the epidemic concludes. Based on current estimates of rates of adverse fetal outcomes among infected women(2,4,5), these results suggest that tens of thousands of pregnancies could be negatively impacted by the first wave of the epidemic. These projections constitute a revised upper limit of populations at risk in the current Zika epidemic, and our approach offers a new way to make rapid assessments of the threat posed by emerging infectious diseases more generally. PMID:27562260

  7. Pulmonary ultrasonographic abnormalities associated with naturally occurring equine influenza virus infection in standardbred racehorses.

    PubMed

    Gross, Diane K; Morley, Paul S; Hinchcliff, Kenneth W; Reichle, Jean K; Slemons, Richard D

    2004-01-01

    The purpose of this investigation was to determine if naturally occurring acute infectious upper respiratory disease (IRD) caused by equine influenza virus is associated with ultrasonographically detectable pleural and pulmonary abnormalities in horses. Standardbred racehorses were evaluated for signs of IRD, defined as acute coughing or mucopurulent nasal discharge. For every horse with IRD (n = 16), 1 or 2 horses with no signs of IRD and the same owner or trainer (n = 30) were included. Thoracic ultrasonography was performed within 5-10 days of the onset of clinical disease in horses with IRD. Horses without IRD were examined at the same time as the horses with IRD with which they were enrolled. The rank of the ultrasound scores of horses with IRD was compared to that of horses without IRD. Equine influenza virus was identified as the primary etiologic agent associated with IRD in this study. Mild lung consolidation and peripheral pulmonary irregularities were found in 11 (69%) of 16 of the horses with IRD and 11 (37%) of 30 of control horses. Lung consolidation (median score = 1) and peripheral irregularities scores (median score = 1) were greater in horses with IRD compared to horses without IRD (median score = 0; P < .05). Pleural effusion was not observed. Equine influenza virus infection can result in abnormalities of the equine lower respiratory tract. Despite the mild nature of IRD observed in this study, lung consolidation and peripheral pulmonary irregularities were more commonly observed in horses with clinical signs of IRD. Further work is needed to determine the clinical significance of these ultrasonographic abnormalities. PMID:15515590

  8. Coregulation mapping based on individual phenotypic variation in response to virus infection

    PubMed Central

    2010-01-01

    Background Gene coregulation across a population is an important aspect of the considerable variability of the human immune response to virus infection. Methodology to investigate it must rely on a number of ingredients ranging from gene clustering to transcription factor enrichment analysis. Results We have developed a methodology to investigate the gene to gene correlations for the expression of 34 genes linked to the immune response of Newcastle Disease Virus (NDV) infected conventional dendritic cells (DCs) from 145 human donors. The levels of gene expression showed a large variation across individuals. We generated a map of gene co-expression using pairwise correlation and multidimensional scaling (MDS). The analysis of these data showed that among the 13 genes left after filtering for statistically significant variations, two clusters are formed. We investigated to what extent the observed correlation patterns can be explained by the sharing of transcription factors (TFs) controlling these genes. Our analysis showed that there was a significant positive correlation between MDS distances and TF sharing across all pairs of genes. We applied enrichment analysis to the TFs having binding sites in the promoter regions of those genes. This analysis, after Gene Ontology filtering, indicated the existence of two clusters of genes (CCL5, IFNA1, IFNA2, IFNB1) and (IKBKE, IL6, IRF7, MX1) that were transcriptionally co-regulated. In order to facilitate the use of our methodology by other researchers, we have also developed an interactive coregulation explorer web-based tool called CorEx. It permits the study of MDS and hierarchical clustering of data combined with TF enrichment analysis. We also offer web services that provide programmatic access to MDS, hierarchical clustering and TF enrichment analysis. Conclusions MDS mapping based on correlation in conjunction with TF enrichment analysis represents a useful computational method to generate predictions underlying gene

  9. The Effects of Plant Virus Infection on Polarization Reflection from Leaves

    PubMed Central

    Maxwell, Daniel J.; Partridge, Julian C.; Roberts, Nicholas W.; Boonham, Neil; Foster, Gary D.

    2016-01-01

    Alteration of leaf surface phenotypes due to virus infection has the potential to affect the likelihood of colonisation by insect vectors, or to affect their feeding activities. The aim of this study was to investigate whether viruses that rely on insects for their transmission, and which can be sensitive to the polarization of light, affect the percentage polarization of light reflected from leaves. We also set out to discover whether a correlation exists between the expression of ECERIFERUM (CER) genes involved in cuticular wax synthesis and the polarization of the light reflected from the leaf surfaces. It was found that the aphid-vectored viruses Potato virus Y and Cucumber mosaic virus (CMV) caused significant reductions in the percentage polarization of light reflected from the abaxial surfaces of leaves of Nicotiana tabacum, whereas the non-insect-vectored viruses Tobacco mosaic virus and Pepino mosaic virus did not induce this effect. In Arabidopsis thaliana, there was little difference in the impacts of CMV and the non-insect-vectored Turnip vein clearing virus on polarization reflection, with both viruses increasing the percentage polarization of light reflected from the abaxial surfaces of leaves. There was a trend towards increased accumulation of CER6 transcripts in N. tabacum and A. thaliana when infected with aphid-vectored viruses. No significant effect of infection on trichome densities was found in A. thaliana, suggesting that alterations to the formation of cuticular waxes may be the more likely phenotypic change on the leaf surface contributing to the changes in polarization reflection. The possible impacts and adaptive significance of these effects with regard to viral transmission by insects are discussed. PMID:27100188

  10. Inhibitory effects of recombinant manganese superoxide dismutase on influenza virus infections in mice.

    PubMed Central

    Sidwell, R W; Huffman, J H; Bailey, K W; Wong, M H; Nimrod, A; Panet, A

    1996-01-01

    The oxygen free-radical scavenger recombinant human manganese superoxide dismutase (MnSOD) was studied for its effects on influenza virus infections in mice when used alone and in combination with ribavirin. Mice challenged with influenza A/NWS/33 (H1N1) virus were treated parenterally in doses of 25, 50, and 100 mg/kg of body weight per day every 8 h for 5 days beginning at 48 h post-virus exposure. An increase in mean day to death, lessened decline in arterial oxygen saturation, and reduced lung consolidation and lung virus titers occurred in the treated animals. To determine the influence of viral challenge, experiments were run in which mice were infected with a 100 or 75% lethal dose of virus and were treated intravenously once daily for 5 days beginning 96 h after virus exposure. Weak inhibition of the mortality rate was seen in mice receiving the high viral challenge, whereas significant inhibition occurred in the animals infected with the lower viral challenge, indicating that MnSOD effects are virus dose dependent. To determine if treatment with small-particle aerosol would render an antiviral effect, infected mice were treated by this route for 1 h daily for 5 days beginning 72 h after virus exposure. A dose-responsive disease inhibition was seen. An infection induced by influenza B/Hong Kong/5/72 virus in mice was mildly inhibited by intravenous MnSOD treatment as seen by increased mean day to death, lessened arterial oxygen saturation decline, and lowered lung consolidation. MnSOD was well tolerated in all experiments. A combination of MnSOD and ribavirin, each administered with small-particle aerosol, resulted in a generally mild improvement of the disease induced by the influenza A virus compared with use of either material alone. PMID:8913477

  11. Serological evidence for avian H9N2 influenza virus infections among Romanian agriculture workers.

    PubMed

    Coman, Alexandru; Maftei, Daniel N; Krueger, Whitney S; Heil, Gary L; Friary, John A; Chereches, Razvan M; Sirlincan, Emanuela; Bria, Paul; Dragnea, Claudiu; Kasler, Iosif; Gray, Gregory C

    2013-12-01

    In recent years, wild birds have introduced multiple highly pathogenic avian influenza (HPAI) H5N1 virus infections in Romanian poultry. In 2005 HPAI infections were widespread among domestic poultry and anecdotal reports suggested domestic pigs may also have been exposed. We sought to examine evidence for zoonotic influenza infections among Romanian agriculture workers. Between 2009 and 2010, 363 adult participants were enrolled in a cross-sectional, seroepidemiological study. Confined animal feeding operation (CAFO) swine workers in Tulcea and small, traditional backyard farmers in Cluj-Napoca were enrolled, as well as a non-animal exposed control group from Cluj-Napoca. Enrollment sera were examined for serological evidence of previous infection with 9 avian and 3 human influenza virus strains. Serologic assays showed no evidence of previous infection with 7 low pathogenic avian influenza viruses or with HPAI H5N1. However, 33 participants (9.1%) had elevated microneutralization antibody titers against avian-like A/Hong Kong/1073/1999(H9N2), 5 with titers ≥ 1:80 whom all reported exposure to poultry. Moderate poultry exposure was significantly associated with elevated titers after controlling for the subjects' age (adjusted OR = 3.6; 95% CI, 1.1-12.1). There was no evidence that previous infection with human H3N2 or H2N2 viruses were confounding the H9N2 seroreactivity. These data suggest that H9N2 virus may have circulated in Romanian poultry and occasionally infected man. PMID:23999337

  12. Clinical evaluation and outcomes of naturally acquired West Nile virus infection in raptors.

    PubMed

    Nemeth, Nicole M; Kratz, Gail E; Bates, Rebecca; Scherpelz, Judy A; Bowen, Richard A; Komar, Nicholas

    2009-03-01

    West Nile virus (WNV) infection and associated disease and mortality have been documented in numerous North American raptor species. Information regarding clinical presentations and long-term outcomes of WNV-infected raptors is important in the clinic for the diagnosis, treatment, and assessment of prognosis, as well as for understanding potential population level effects on raptor species. Raptors of 22 species admitted to a rehabilitation clinic were tested, from 2002 to 2005, for previous and acute WNV infection, while comparing clinical syndromes, trauma, and rehabilitation outcomes. Forty-two percent of admitted raptors (132/314) had been infected with WNV, and these presented with a WNV-attributed clinical disease rate of 67.4% (89/132). West Nile virus-infected raptors were less likely to be released (79/132 [59.8%]) than negative raptors (138/182 [75.8%]) and more likely to die or be euthanized (47/132 [35.6%] for WNV-infected vs. 32/182 [17.6%] for WNV-negative). However, WNV-infected raptors with neurologic disease were no less likely to be released (29/53 [54.7%]) than those without neurologic disease (50/79 [63.3%]). Clinical WNV-associated syndromes varied among species. Great horned owls (Bubo virginianus) were more likely to have neurologic signs, whereas American kestrels (Falco sparverius) and Swainson's hawks (Buteo swainsonii) were less likely to have neurologic signs. These results suggest that free-ranging raptors are frequently infected with WNV and that clinical syndromes differ among species. WNV has potentially devastating effects on raptors; however, rehabilitation of WNV-infected raptors can lead to positive outcomes, even for those having had severe neurologic disease. PMID:19368240

  13. Blockade of immunosuppressive cytokines restores NK cell antiviral function in chronic hepatitis B virus infection.

    PubMed

    Peppa, Dimitra; Micco, Lorenzo; Javaid, Alia; Kennedy, Patrick T F; Schurich, Anna; Dunn, Claire; Pallant, Celeste; Ellis, Gidon; Khanna, Pooja; Dusheiko, Geoffrey; Gilson, Richard J; Maini, Mala K

    2010-01-01

    NK cells are enriched in the liver, constituting around a third of intrahepatic lymphocytes. We have previously demonstrated that they upregulate the death ligand TRAIL in patients with chronic hepatitis B virus infection (CHB), allowing them to kill hepatocytes bearing TRAIL receptors. In this study we investigated whether, in addition to their pathogenic role, NK cells have antiviral potential in CHB. We characterised NK cell subsets and effector function in 64 patients with CHB compared to 31 healthy controls. We found that, in contrast to their upregulated TRAIL expression and maintenance of cytolytic function, NK cells had a markedly impaired capacity to produce IFN-γ in CHB. This functional dichotomy of NK cells could be recapitulated in vitro by exposure to the immunosuppressive cytokine IL-10, which was induced in patients with active CHB. IL-10 selectively suppressed NK cell IFN-γ production without altering cytotoxicity or death ligand expression. Potent antiviral therapy reduced TRAIL-expressing CD56(bright) NK cells, consistent with the reduction in liver inflammation it induced; however, it was not able to normalise IL-10 levels or the capacity of NK cells to produce the antiviral cytokine IFN-γ. Blockade of IL-10 +/- TGF-β restored the capacity of NK cells from both the periphery and liver of patients with CHB to produce IFN-γ, thereby enhancing their non-cytolytic antiviral capacity. In conclusion, NK cells may be driven to a state of partial functional tolerance by the immunosuppressive cytokine environment in CHB. Their defective capacity to produce the antiviral cytokine IFN-γ persists in patients on antiviral therapy but can be corrected in vitro by IL-10+/- TGF-β blockade. PMID:21187913

  14. Small RNA Analysis in Sindbis Virus Infected Human HEK293 Cells

    PubMed Central

    Dalmay, Tamas; Powell, Penny P.

    2013-01-01

    Introduction In contrast to the defence mechanism of RNA interference (RNAi) in plants and invertebrates, its role in the innate response to virus infection of mammals is a matter of debate. Since RNAi has a well-established role in controlling infection of the alphavirus Sindbis virus (SINV) in insects, we have used this virus to investigate the role of RNAi in SINV infection of human cells. Results SINV AR339 and TR339-GFP were adapted to grow in HEK293 cells. Deep sequencing of small RNAs (sRNAs) early in SINV infection (4 and 6 hpi) showed low abundance (0.8%) of viral sRNAs (vsRNAs), with no size, sequence or location specific patterns characteristic of Dicer products nor did they possess any discernible pattern to ascribe to a specific RNAi biogenesis pathway. This was supported by multiple variants for each sequence, and lack of hot spots along the viral genome sequence. The abundance of the best defined vsRNAs was below the limit of Northern blot detection. The adaptation of the virus to HEK293 cells showed little sequence changes compared to the reference; however, a SNP in E1 gene with a preference from G to C was found. Deep sequencing results showed little variation of expression of cellular microRNAs (miRNAs) at 4 and 6 hpi compared to uninfected cells. Twelve miRNAs exhibiting some minor differential expression by sequencing, showed no difference in expression by Northern blot analysis. Conclusions We show that, unlike SINV infection of invertebrates, generation of Dicer-dependent svRNAs and change in expression of cellular miRNAs were not detected as part of the Human response to SINV. PMID:24391886

  15. Neuropathology of JC virus infection in progressive multifocal leukoencephalopathy in remission

    PubMed Central

    SantaCruz, Karen S; Roy, Gulmohor; Spigel, James; Bearer, Elaine L

    2016-01-01

    AIM: To investigate the neuropathology of the brain in a rare case of remission following diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: Consent from the family for an autopsy was obtained, clinical records and radiograms were retrieved. A complete autopsy was performed, with brain examination after fixation and coronal sectioning at 1 cm intervals. Fourteen regions were collected for paraffin embedding and staining for microscopic analysis. Histologic sections were stained with Luxol blue, hematoxylin/eosin, and immunostained for myelin basic protein, neurofilament, SV40 T antigen and p53. The biopsy material was also retrieved and sections were stained with hematoxylin/eosin and immunostained for SV40 and p53. Sections were examined by American Board of Pathology certified pathologists and images captured digitally. RESULTS: Review of the clinical records was notable for a history of ulcerative colitis resulting in total colectomy in 1977 and a liver transplant in 1998 followed by immune-suppressive therapy. Neurological symptoms presented immediately, therefore a biopsy was obtained which was diagnosed as PML. Immunotherapy was adjusted and clinical improvement was noted. No subsequent progression was reported. Review of the biopsy demonstrated atypical astrocytes and enlarged hyperchromatic oligodendroglial cells consistent with JC virus infection. Strong SV40 and p53 staining was found in glial cells and regions of dense macrophage infiltration were present. On gross examination of the post-mortem brain, a lesion in the same site as the original biopsy in the cerebellum was identified but no other lesions in the brain were found. Microscopic analysis of this cerebellar lesion revealed a loss of myelin and axons, and evidence of axonal damage. This single burned-out lesion was equivocally positive for SV40 antigen with little p53 staining. Examination of thirteen other brain regions found no other occult sites. CONCLUSION: Our study

  16. Zooplankton may serve as transmission vectors for viruses infecting algal blooms in the ocean.

    PubMed

    Frada, Miguel José; Schatz, Daniella; Farstey, Viviana; Ossolinski, Justin E; Sabanay, Helena; Ben-Dor, Shifra; Koren, Ilan; Vardi, Assaf

    2014-11-01

    Marine viruses are recognized as a major driving force regulating phytoplankton community composition and nutrient cycling in the oceans. Yet, little is known about mechanisms that influence viral dispersal in aquatic systems, other than physical processes, and that lead to the rapid demise of large-scale algal blooms in the oceans. Here, we show that copepods, abundant migrating crustaceans that graze on phytoplankton, as well as other zooplankton can accumulate and mediate the transmission of viruses infecting Emiliania huxleyi, a bloom-forming coccolithophore that plays an important role in the carbon cycle. We detected by PCR that >80% of copepods collected during a North Atlantic E. huxleyi bloom carried E. huxleyi virus (EhV) DNA. We demonstrated by isolating a new infectious EhV strain from a copepod microbiome that these viruses are infectious. We further showed that EhVs can accumulate in high titers within zooplankton guts during feeding or can be adsorbed to their surface. Subsequently, EhV can be dispersed by detachment or via viral-dense fecal pellets over a period of 1 day postfeeding on EhV-infected algal cells, readily infecting new host populations. Intriguingly, the passage through zooplankton guts prolonged EhV's half-life of infectivity by 35%, relative to free virions in seawater, potentially enhancing viral transmission. We propose that zooplankton, swimming through topographically adjacent phytoplankton micropatches and migrating daily over large areas across physically separated water masses, can serve as viral vectors, boosting host-virus contact rates and potentially accelerating the demise of large-scale phytoplankton blooms. PMID:25438947

  17. Systems Analysis of a RIG-I Agonist Inducing Broad Spectrum Inhibition of Virus Infectivity

    PubMed Central

    Goulet, Marie-Line; Olagnier, David; Xu, Zhengyun; Paz, Suzanne; Belgnaoui, S. Mehdi; Lafferty, Erin I.; Janelle, Valérie; Arguello, Meztli; Paquet, Marilene; Ghneim, Khader; Richards, Stephanie; Smith, Andrew; Wilkinson, Peter; Cameron, Mark; Kalinke, Ulrich; Qureshi, Salman; Lamarre, Alain; Haddad, Elias K.; Sekaly, Rafick Pierre; Peri, Suraj; Balachandran, Siddharth; Lin, Rongtuan; Hiscott, John

    2013-01-01

    The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5′ triphosphate (5′ppp) terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5′pppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, and induction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN) signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5′pppRNA, and not by IFNα-2b, that included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5′pppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5′pppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach provides transcriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5′pppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents. PMID:23633948

  18. Isolation and Characterization of a Single-Stranded DNA Virus Infecting Chaetoceros lorenzianus Grunow▿

    PubMed Central

    Tomaru, Yuji; Takao, Yoshitake; Suzuki, Hidekazu; Nagumo, Tamotsu; Koike, Kanae; Nagasaki, Keizo

    2011-01-01

    Diatoms are one of the most significant primary producers in the ocean, and the importance of viruses as a potential source of mortality for diatoms has recently been recognized. Thus far, eight different diatom viruses infecting the genera Rhizosolenia and Chaetoceros have been isolated and characterized to different extents. We report the isolation of a novel diatom virus (ClorDNAV), which causes the lysis of the bloom-forming species Chaetoceros lorenzianus, and show its physiological, morphological, and genomic characteristics. The free virion was estimated to be ∼34 nm in diameter. The arrangement of virus particles appearing in cross-section was basically a random aggregation in the nucleus. Occasionally, distinctive formations such as a ring-like array composed of 9 or 10 spherical virions or a centipede-like array composed of rod-shaped particles were also observed. The latent period and the burst size were estimated to be <48 h and 2.2 × 104 infectious units per host cell, respectively. ClorDNAV harbors a covalently closed circular single-stranded DNA (ssDNA) genome (5,813 nucleotides [nt]) that includes a partially double-stranded DNA region (979 nt). At least three major open reading frames were identified; one showed a high similarity to putative replicase-related proteins of the other ssDNA diatom viruses, Chaetoceros salsugineum DNA virus (previously reported as CsNIV) and Chaetoceros tenuissimus DNA virus. ClorDNAV is the third member of the closed circular ssDNA diatom virus group, the genus Bacilladnavirus. PMID:21666026

  19. Prevalence of rabies virus and Hantaan virus infections in commensal rodents and shrews trapped in Bangkok.

    PubMed

    Kantakamalakul, Wannee; Siritantikorn, Sontana; Thongcharoen, Prasert; Singchai, Chantra; Puthavathana, Pilaipan

    2003-11-01

    Five hundred rodents and shrews (Rattus norvegicus: 458, Rattus rattus: 28, Rattus exulans: 5, Mus musculus: 4 and Suncus murine: 5) trapped from the fresh food markets around Bangkok area were investigated for rabies virus and Hantaan virus infections. No rabies viral antigens in the animals' brains were detected by direct immunofluorescence. On the other hand, antibodies to Hantaan virus were demonstrated in the sera of 7 (1.53%) R. norvegicus caught in various markets using a particle agglutination technique. Further determination of the viral genome in rat lung tissue was performed by reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR, 3 (0.66%) out of 7 were positive. HindIII and HifI restriction enzyme analyses showed the pattern of the Hantaan virus genome in 2 samples and that of the Seoul virus genome in the other. The results of the present study suggest that rodents from Bangkok's fresh food markets did not carry rabies. Thus, getting rid of rabies in dogs or cats in the Bangkok area may be easier than anticipated because there are no sources of asymptomatic reservoirs. This may result in the low incidence of rabies patients observed in Bangkok. On the contrary, the presence of antibodies and the Hantaan virus genome and Seoul virus genome in R. norvegicus will definitely provide evidence for physicians to be aware of hemorrhagic fever with renal syndrome (HFRS) and other clinical settings of Hantaan/Seoul virus disease in patients with a history of having contact with rats or their excreta. PMID:14696782

  20. A Systems Immunology Approach to Plasmacytoid Dendritic Cell Function in Cytopathic Virus Infections

    PubMed Central

    Bocharov, Gennady; Züst, Roland; Cervantes-Barragan, Luisa; Luzyanina, Tatyana; Chiglintsev, Egor; Chereshnev, Valery A.; Thiel, Volker; Ludewig, Burkhard

    2010-01-01

    Plasmacytoid dendritic cell (pDC)-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analysis of the structure, dynamics and operating principles of virus-host interactions which constrain the initial spread of the pathogen. Using high-resolution experimental data sets coming from the well-described mouse hepatitis virus (MHV) model, we first calibrated basic modules including MHV infection of its primary target cells, i.e. pDCs and macrophages (Mφs). These basic building blocks were used to generate and validate an integrative mathematical model for in vivo infection dynamics. Parameter estimation for the system indicated that on a per capita basis, one infected pDC secretes sufficient type I IFN to protect 103 to 104 Mφs from cytopathic viral infection. This extremely high protective capacity of pDCs secures the spleen's capability to function as a ‘sink’ for the virus produced in peripheral organs such as the liver. Furthermore, our results suggest that the pDC population in spleen ensures a robust protection against virus variants which substantially down-modulate IFN secretion. However, the ability of pDCs to protect against severe disease caused by virus variants exhibiting an enhanced liver tropism and higher replication rates appears to be rather limited. Taken together, this systems immunology analysis suggests that antiviral therapy against cytopathic viruses should primarily limit viral replication within peripheral target organs. PMID:20661432

  1. Protection of mice against encephalomyocarditis virus infection by preparations of transfer RNA.

    PubMed

    Stebbing, N; Grantham, C A; Kaminski, F; Lindley, I J

    1977-01-01

    Preparations of bacterial transfer RNA (tRNA), give dose-dependent protection of mice against encephalomyocarditis (EMC) virus infection at up to I mg tRNA per mouse with maximum response when the tRNA is administered around 6 h before infection. Protection occurs with intraperitoneally and intravenously administered tRNA against infections by both these routes. In some experiments significant protection occurs by single treatments of tRNA up to 24 h after infection with virus doses of I X LD100. Some tRNA preparations of eukaryotic origin do not give significant protection. Protection is not a feature of all species of bacterial tRNA; partially purified valine, tyrosine and phenylalanine tRNAs from Escherichia coli are not protective. tRNA treatment does not induce circulating interferon nor does it 'hypo-reactivate' the protective effect of poly (I).poly (C) treatment of mice. Humoral and cell mediated immune responses do not seem to be involved in tRNA mediated protection since first, cytosine arabinoside treatment does not affect protection by tRNA; second, serum from mice treated with tRNA and an EMC vaccine does not protect other mice against infection, and third, mice that survive normally lethal infections as a result of tRNA treatment are generally just as susceptible to re-infection as previously untreated, uninfected mice. Silica treatment abolishes protection of mice by tRNA implying that macrophages are necessary. However, tRNA does not seem to act by clearance of virus particles since vaccination of mice by inactivated EMC virus is not affected by tRNA treatment. These results are considered in relation to the presence of a tRNA-like structure in EMC virus RNA and protection of mice by other single stranded polynucleotides. PMID:188982

  2. Suppression of in vivo cell-mediated immunity during experimental influenza A virus infection of adults.

    PubMed

    Skoner, D P; Angelini, B L; Jones, A; Seroky, J; Doyle, W J; Fireman, P

    1996-12-20

    A variety of recent evidence documents that otitis media is a frequent complication of upper respiratory tract viral infections. This relationship has been attributed to the interaction of a number of virus-provoked host responses, including eustachian tube dysfunction, changes in nasopharyngeal bacterial flora and suppressed immune function. The present study examined the effect of experimental influenza A virus infection on immune function as assessed by delayed skin test reactivity to candida, tetanus, and diphtheria/tetanus antigens in healthy adults with (n = 12) and without (n = 15) allergic rhinitis. All subjects became infected with the challenge virus as evidenced by viral shedding into nasal secretions and/or a four-fold rise in convalescent serum antibody titers compared to baseline. Intradermal skin tests were placed at baseline and 2, 4, 17, and 24 days after intranasal influenza A inoculation, the reactions were imaged and recorded 48 h after placement, and response areas were calculated by computerized digitization. The average combined areas for the three antigens (+/- S.T.D.) on each of the 5 study days were 1.4 +/- 1.4, 0.7 +/- 0.7, 0.6 +/- 0.6, 1.4 +/- 1.4, and 1.2 +/- 1.2 cm2, respectively. The responses to candida, but not tetanus and diphtheria/tetanus, returned to baseline levels by day 17. Repeated measures ANOVA documented significant effects of study day and antigen, but not allergy status. These results show that experimental influenza A infection suppressed delayed hypersensitivity skin tests in both allergic and non-allergic subjects, and suggest that alterations in immune function may contribute to otitis media. PMID:9119602

  3. A Patient Presenting with Tuberculous Encephalopathy and Human Immunodeficiency Virus Infection

    PubMed Central

    Li, Jason; Afroz, Suraiya; French, Eric; Mehta, Anuj

    2016-01-01

    Patient: Male, 33 Final Diagnosis: Tuberculous meningitis, human immunodeficiency virus infection Symptoms: — Medication: — Clinical Procedure: Lumbar puncture Specialty: Infectious Diseases Objective: Rare disease Background: In the USA, Mycobacterium tuberculosis infection is more likely to be found in foreign-born individuals, and those co-infected with human immunodeficiency virus (HIV) are more likely to have tuberculous meningitis. The literature is lacking in details about the clinical workup of patients presenting with tuberculous meningitis with encephalopathic features who are co-infected with HIV. This report demonstrates a clinical approach to diagnosis and management of tuberculous meningitis. Case Report: A 33-year-old Ecuadorean man presented with altered consciousness and constitutional symptoms. During the workup he was found to have tuberculous meningitis with encephalopathic features and concurrent HIV infection. Early evidence for tuberculosis meningitis included lymphocytic pleocytosis and a positive interferon gamma release assay. A confirmatory diagnosis of systemic infection was made based on lymph node biopsy. Imaging studies of the neck showed scrofula and adenopathy, and brain imaging showed infarctions, exudates, and communicating hydrocephalus. Treatment was started for tuberculous meningitis, while antiretroviral therapy for HIV was started 5 days later in combination with prednisone, given the risk of immune reconstitution inflammatory syndrome (IRIS). Conclusions: A clinical picture consistent with tuberculous meningitis includes constitutional symptoms, foreign birth, lymphocytic pleocytosis, specific radiographic findings, and immunodeficiency. Workup for tuberculous meningitis should include MRI, HIV screening, and cerebral spinal fluid analysis. It is essential to treat co-infection with HIV and to assess for IRIS. PMID:27302013

  4. Antibodies Targeting Novel Neutralizing Epitopes of Hepatitis C Virus Glycoprotein Preclude Genotype 2 Virus Infection.

    PubMed

    Deng, Kai; Liu, Ruyu; Rao, Huiying; Jiang, Dong; Wang, Jianghua; Xie, Xingwang; Wei, Lai

    2015-01-01

    Currently, there is no effective vaccine to prevent hepatitis C virus (HCV) infection, partly due to our insufficient understanding of the virus glycoprotein immunology. Most neutralizing antibodies (nAbs) were identified using glycoprotein immunogens, such as recombinant E1E2, HCV pseudoparticles or cell culture derived HCV. However, the fact that in the HCV acute infection phase, only a small proportion of patients are self-resolved accompanied with the emergence of nAbs, indicates the limited immunogenicity of glycoprotein itself to induce effective antibodies against a highly evolved virus. Secondly, in previous reports, the immunogen sequence was mostly the genotype of the 1a H77 strain. Rarely, other genotypes/subtypes have been studied, although theoretically one genotype/subtype immunogen is able to induce cross-genotype neutralizing antibodies. To overcome these drawbacks and find potential novel neutralizing epitopes, 57 overlapping peptides encompassing the full-length glycoprotein E1E2 of subtype 1b were synthesized to immunize BALB/c mice, and the neutralizing reactive of the induced antisera against HCVpp genotypes 1-6 was determined. We defined a domain comprising amino acids (aa) 192-221, 232-251, 262-281 and 292-331 of E1, and 421-543, 564-583, 594-618 and 634-673 of E2, as the neutralizing regions of HCV glycoprotein. Peptides PUHI26 (aa 444-463) and PUHI45 (aa 604-618)-induced antisera displayed the most potent broad neutralizing reactive. Two monoclonal antibodies recognizing the PUHI26 and PUHI45 epitopes efficiently precluded genotype 2 viral (HCVcc JFH and J6 strains) infection, but they did not neutralize other genotypes. Our study mapped a neutralizing epitope region of HCV glycoprotein using a novel immunization strategy, and identified two monoclonal antibodies effective in preventing genotype 2 virus infection. PMID:26406225

  5. Serological evidence of hepatitis E virus infection in different animal species from the Southeast of Brazil.

    PubMed

    Vitral, Cláudia L; Pinto, Marcelo A; Lewis-Ximenez, Lia L; Khudyakov, Yuri E; dos Santos, Débora R; Gaspar, Ana Maria C

    2005-04-01

    Serological evidence of hepatitis E virus infection (HEV) has been observed in both humans and different animal species living in non-endemic areas, suggesting that animals could be important reservoir for virus transmission to man. Antibodies to HEV have been detected in some Brazilian population groups. Nevertheless, sporadic cases of acute HEV infection have never been reported. We collected 271 serum samples from several domestic animals and also from pig handlers from Southeast of Brazil in order to investigate the seroprevalence of HEV infection. Anti-HEV IgG was detected in cows (1.42%), dogs (6.97%), chickens (20%), swines (24.3%), and rodents (50%), as well as in pig handlers (6.3%). The recognition of swine HEV infections in pigs in many countries of the world led us to investigate a larger sample of pigs (n = 357) from the same Brazilian region with ages ranging from 1 to > 25 weeks. IgG anti-HEV was detected in 100% of 7-day old pigs. Following a gradual decline between weeks 2 and 8 (probably due to loss of maternal IgG), the prevalence then steady increased until it reached 97.3% of animals older than 25 weeks. Besides the detection of anti-HEV antibodies in different animal species, the results showed that swine HEV infection seems to be almost universal within this Brazilian pig population. This is the first report that shows evidences of HEV circulation in Brazilian animal species and pig handlers. PMID:16021297

  6. Ebola virus-like particles protect from lethal Ebola virus infection

    PubMed Central

    Warfield, Kelly L.; Bosio, Catharine M.; Welcher, Brent C.; Deal, Emily M.; Mohamadzadeh, Mansour; Schmaljohn, Alan; Aman, M. Javad; Bavari, Sina

    2003-01-01

    The filovirus Ebola causes hemorrhagic fever with 70–80% human mortality. High case-fatality rates, as well as known aerosol infectivity, make Ebola virus a potential global health threat and possible biological warfare agent. Development of an effective vaccine for use in natural outbreaks, response to biological attack, and protection of laboratory workers is a higher national priority than ever before. Coexpression of the Ebola virus glycoprotein (GP) and matrix protein (VP40) in mammalian cells results in spontaneous production and release of virus-like particles (VLPs) that resemble the distinctively filamentous infectious virions. VLPs have been tested and found efficacious as vaccines for several viruses, including papillomavirus, HIV, parvovirus, and rotavirus. Herein, we report that Ebola VLPs (eVLPs) were immunogenic in vitro as eVLPs matured and activated mouse bone marrow-derived dendritic cells, assessed by increases in cell-surface markers CD40, CD80, CD86, and MHC class I and II and secretion of IL-6, IL-10, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor α by the dendritic cells. Further, vaccinating mice with eVLPs activated CD4+ and CD8+ T cells, as well as CD19+ B cells. After vaccination with eVLPs, mice developed high titers of Ebola virus-specific antibodies, including neutralizing antibodies. Importantly, mice vaccinated with eVLPs were 100% protected from an otherwise lethal Ebola virus inoculation. Together, our data suggest that eVLPs represent a promising vaccine candidate for protection against Ebola virus infections and a much needed tool to examine the genesis and nature of immune responses to Ebola virus. PMID:14673108

  7. Inhibition of Hepatitis C Virus Infection by DNA Aptamer against Envelope Protein

    PubMed Central

    Yang, Darong; Meng, Xianghe; Yu, Qinqin; Xu, Li; Long, Ying; Liu, Bin; Fang, Xiaohong

    2013-01-01

    Hepatitis C virus (HCV) envelope protein (E1E2) is essential for virus binding to host cells. Aptamers have been demonstrated to have strong promising applications in drug development. In the current study, a cDNA fragment encoding the entire E1E2 gene of HCV was cloned. E1E2 protein was expressed and purified. Aptamers for E1E2 were selected by the method of selective evolution of ligands by exponential enrichment (SELEX), and the antiviral actions of the aptamers were examined. The mechanism of their antiviral activity was investigated. The data show that selected aptamers for E1E2 specifically recognize the recombinant E1E2 protein and E1E2 protein from HCV-infected cells. CD81 protein blocks the binding of aptamer E1E2-6 to E1E2 protein. Aptamers against E1E2 inhibit HCV infection in an infectious cell culture system although they have no effect on HCV replication in a replicon cell line. Beta interferon (IFN-β) and IFN-stimulated genes (ISGs) are not induced in virus-infected hepatocytes with aptamer treatment, suggesting that E1E2-specific aptamers do not induce innate immunity. E2 protein is essential for the inhibition of HCV infection by aptamer E1E2-6, and the aptamer binding sites are located in E2. Q412R within E1E2 is the major resistance substitution identified. The data indicate that an aptamer against E1E2 exerts its antiviral effects through inhibition of virus binding to host cells. Aptamers against E1E2 can be used with envelope protein to understand the mechanisms of HCV entry and fusion. The aptamers may hold promise for development as therapeutic drugs for hepatitis C patients. PMID:23877701

  8. Incidence of dengue virus infection among Japanese travellers, 2006 to 2010

    PubMed Central

    Arima, Yuzo; Shimada, Tomoe; Matsui, Tamano; Tada, Yuki; Okabe, Nobuhiko

    2012-01-01

    Introduction Dengue continues to be a global public health concern. In Japan, although dengue cases are currently seen only among travellers returning from endemic areas, the number of reported cases is rising according to the national case-based surveillance system. We evaluated the characteristics of dengue cases imported into Japan and the relationship between the incidence of infection and season of travel to popular destinations. Methods Dengue cases reported to the national surveillance system were retrospectively examined. The number of reported cases per number of Japanese travellers to a dengue-endemic country was calculated to estimate the country-specific incidence of imported dengue virus infection. The incidence of dengue infection among Japanese travellers was compared between dengue high season and low season in each country using relative risk (RR) and associated 95% confidence intervals (CI). Results Among 540 Japanese residents who were reported as dengue cases from 2006 to 2010, the majority had travelled to Indonesia, India, the Philippines and Thailand. The RR of dengue infection among Japanese travellers during dengue high season versus low season was 4.92 (95% CI: 3.01–8.04) for the Philippines, 2.76 (95% CI: 1.67–4.54) for Thailand and 0.37 (95% CI: 0.15–0.92) for Indonesia. Discussion Overall, higher incidence of imported cases appeared to be related to historic dengue high seasons. Travellers planning to visit dengue-endemic countries should be aware of historic dengue seasonality and the current dengue situation. PMID:23908911

  9. High prevalence of chronic hepatitis D virus infection in Eastern Turkey: urbanization of the disease

    PubMed Central

    Dulger, Ahmet Cumhur; Suvak, Burak; Gonullu, Edip; Gultepe, Bilge; Aydın, İbrahim; Batur, Abdüssamet; Karadas, Sevdegul; Olmez, Şehmus

    2016-01-01

    Introduction Both hepatitis B virus (HBV) and hepatitis D virus (HDV) infection play an increasingly important role in liver diseases. The main objective of this study was to investigate the socio-epidemiological, laboratory and radiological aspects of both HBV and HDV infection near the Iranian border of Turkey. Material and methods The study included 3352 patients with HBV and HDV infection. Socioepidemiological, laboratory and radiological aspects of the study subjects were retrospectively examined. Comorbid metabolic diseases were not assessed due to the retrospective design of the study. Results Most of the study subjects were HBe antigen negative. No significant difference in terms of HBV-DNA levels or HBe antigen seropositivity was detected between the city centre and rural areas (p > 0.005). The mean HBV-DNA level in the anti-HDV-positive group was significantly lower than in the anti-HDV-negative group (p < 0.001). The rate of HDV-RNA positivity in women was higher than in their male counterparts (p = 0.017). Anti-HDV-IgG was detected in 18.4% of tested subjects who came from an urban area. In contrast, 12.5% of subjects of the rural group had a positive result for anti-HDV-IgG. Among 134 ultrasonographically evaluated delta hepatitis patients, 37.3% had liver cirrhosis. On the other hand, in 1244 patients with hepatitis B monoinfection, there were 90 patients with liver cirrhosis. Radiologically, the rate of hepatic steatosis in delta hepatitis patients was lower than in those with HBV monoinfection. Conclusions Hepatitis D virus infection was particularly prevalent among the urban population as well as in female subjects. More broadly, the current observations are the first to suggest an inverse correlation between delta hepatitis and ultrasonography-proven hepatic steatosis. PMID:27186189

  10. Characterization of the soluble glycoprotein released from vesicular stomatitis virus-infected cells.

    PubMed Central

    Chatis, P A; Morrison, T G

    1983-01-01

    Vesicular stomatitis virus-infected Chinese hamster ovary cells release into the extracellular medium a soluble form of the vesicular stomatitis virus glycoprotein (G protein) termed Gs (Kang and Prevec, Virology 46:678-680, 1971). The properties of this molecule and the cellular site at which it is generated were characterized. By comparing the sizes and the peptide maps of the unglycosylated forms of G and Gs, we found that between 5,000 and 6,000 daltons of the carboxy-terminal end of the G protein is cleaved to generate the Gs molecule. This truncated molecule contains no fatty acid. Gs released from cells grown at 39 degrees C migrated on polyacrylamide gels slightly slower than Gs released at 30 degrees C. The unglycosylated form of Gs also showed this size difference. Furthermore, unglycosylated Gs was resolved into two species upon isoelectric focusing: the relative amounts of the two species depended upon the temperature at which infected cells were incubated. Full-sized unglycosylated virus-associated G also was resolved into two species, but the more basic form predominated at both 30 and 39 degrees C. The appearance of Gs in the extracellular medium depended upon the presence of stable, full-sized G at the cell surface. The amount of Gs released was quantitated in seven different situations in which the migration of G to the cell surface was inhibited. In all cases, the amount of Gs released was also decreased. In addition, incubation of cells surface labeled with 125I resulted in the release of 125I-labeled Gs protein, as well as full-sized G protein. These results suggest that Gs is generated primarily by proteolytic cleavage of plasma membrane-associated G at a site in the molecule just amino terminal to the membrane-spanning region of the molecule. Images PMID:6296461

  11. Antibodies Targeting Novel Neutralizing Epitopes of Hepatitis C Virus Glycoprotein Preclude Genotype 2 Virus Infection

    PubMed Central

    Rao, Huiying; Jiang, Dong; Wang, Jianghua; Xie, Xingwang; Wei, Lai

    2015-01-01

    Currently, there is no effective vaccine to prevent hepatitis C virus (HCV) infection, partly due to our insufficient understanding of the virus glycoprotein immunology. Most neutralizing antibodies (nAbs) were identified using glycoprotein immunogens, such as recombinant E1E2, HCV pseudoparticles or cell culture derived HCV. However, the fact that in the HCV acute infection phase, only a small proportion of patients are self-resolved accompanied with the emergence of nAbs, indicates the limited immunogenicity of glycoprotein itself to induce effective antibodies against a highly evolved virus. Secondly, in previous reports, the immunogen sequence was mostly the genotype of the 1a H77 strain. Rarely, other genotypes/subtypes have been studied, although theoretically one genotype/subtype immunogen is able to induce cross-genotype neutralizing antibodies. To overcome these drawbacks and find potential novel neutralizing epitopes, 57 overlapping peptides encompassing the full-length glycoprotein E1E2 of subtype 1b were synthesized to immunize BALB/c mice, and the neutralizing reactive of the induced antisera against HCVpp genotypes 1–6 was determined. We defined a domain comprising amino acids (aa) 192–221, 232–251, 262–281 and 292–331 of E1, and 421–543, 564–583, 594–618 and 634–673 of E2, as the neutralizing regions of HCV glycoprotein. Peptides PUHI26 (aa 444–463) and PUHI45 (aa 604–618)-induced antisera displayed the most potent broad neutralizing reactive. Two monoclonal antibodies recognizing the PUHI26 and PUHI45 epitopes efficiently precluded genotype 2 viral (HCVcc JFH and J6 strains) infection, but they did not neutralize other genotypes. Our study mapped a neutralizing epitope region of HCV glycoprotein using a novel immunization strategy, and identified two monoclonal antibodies effective in preventing genotype 2 virus infection. PMID:26406225

  12. Influenza virus infection in mice after exposure to coal dust and diesel engine emissions

    SciTech Connect

    Hahon, N.; Booth, J.A.; Green, F.; Lewis, T.R.

    1985-06-01

    Influenza virus infection initiated after aerosol exposure of CD-1, white Swiss mice for durations of 1, 3, and 6 months to respirable particulates maintained at 2 mg/m3 of either coal dust (CD), diesel engine emissions (DEE), a combination of both (CD/DEE), or to filtered air (control) was studied. The course of infection in mice previously exposed for 1 month to various particulates did not differ appreciably among the four animal groups with respect to mortality, virus growth in lungs, interferon levels, or hemagglutinin antibody response. In mice exposed for 3 and 6 months to different particulates, the mortality response was similar among all animal groups. However, the percentage of animals showing lung consolidation was significantly higher in the 3-month groups exposed to DEE (96.5%) and CD/DEE (97%) than in the control (61.2%); in the 6-month groups, the percentages were twice that of the control for both DEE- and CD/DEE-exposed animals. Complementing these observations of both 3- and 6-month-exposed animals was the higher virus growth levels attained in the DEE and CD/DEE animals with concomitant depressed interferon levels which were the inverse of findings noted in the control group. Hemagglutinin-antibody levels in particulate-exposed animals, especially at the 6-month interval, were fourfold less than the control. Histopathologic examination of lungs revealed no qualitative differences in the inflammatory response at any one specified time interval of exposure to influenza virus among the control and particulate-exposed animal groups. However, there were differences in severity of reaction in relation to the particulate component of the exposures. Focal macular collections of pigment-laden macrophages were seen only in DEE and CD/DEE but not in CD animals after 3- and 6-month exposures.

  13. The Effects of Plant Virus Infection on Polarization Reflection from Leaves.

    PubMed

    Maxwell, Daniel J; Partridge, Julian C; Roberts, Nicholas W; Boonham, Neil; Foster, Gary D

    2016-01-01

    Alteration of leaf surface phenotypes due to virus infection has the potential to affect the likelihood of colonisation by insect vectors, or to affect their feeding activities. The aim of this study was to investigate whether viruses that rely on insects for their transmission, and which can be sensitive to the polarization of light, affect the percentage polarization of light reflected from leaves. We also set out to discover whether a correlation exists between the expression of ECERIFERUM (CER) genes involved in cuticular wax synthesis and the polarization of the light reflected from the leaf surfaces. It was found that the aphid-vectored viruses Potato virus Y and Cucumber mosaic virus (CMV) caused significant reductions in the percentage polarization of light reflected from the abaxial surfaces of leaves of Nicotiana tabacum, whereas the non-insect-vectored viruses Tobacco mosaic virus and Pepino mosaic virus did not induce this effect. In Arabidopsis thaliana, there was little difference in the impacts of CMV and the non-insect-vectored Turnip vein clearing virus on polarization reflection, with both viruses increasing the percentage polarization of light reflected from the abaxial surfaces of leaves. There was a trend towards increased accumulation of CER6 transcripts in N. tabacum and A. thaliana when infected with aphid-vectored viruses. No significant effect of infection on trichome densities was found in A. thaliana, suggesting that alterations to the formation of cuticular waxes may be the more likely phenotypic change on the leaf surface contributing to the changes in polarization reflection. The possible impacts and adaptive significance of these effects with regard to viral transmission by insects are discussed. PMID:27100188

  14. Prevalence of occult hepatitis C virus infection in Iranian patients with beta thalassemia major.

    PubMed

    Bastani, Mohammad-Navid; Bokharaei-Salim, Farah; Keyvani, Hossein; Esghaei, Maryam; Monavari, Seyed Hamidreza; Ebrahimi, Mojtaba; Garshasebi, Saba; Fakhim, Shahin

    2016-07-01

    Occult hepatitis C virus infection (OCI) is a new pathological form of chronic hepatitis virus (HCV) infection characterized by the presence of HCV RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) specimens and the absence of HCV RNA and anti-HCV antibodies (Abs) in plasma samples. β-thalassemia major is a hereditary recessive blood disease with deficiency in the hemoglobin beta chain. Thalassemic patients need blood transfusion therapy; repeated blood transfusion increases the risk of viral blood-borne infection. The aim of this study was to determine the prevalence of OCI in Iranian patients with β-thalassemia major. From February 2015 to November 2015, a total of 147 Iranian patients with β-thalassemia major were enrolled in this cross-sectional study. After extraction of viral RNA from the plasma and PBMC samples, HCV genomic RNA in the specimens was amplified by RT-nested PCR using primers from the 5'-UTR. The HCV genotypes of the positive specimens were tested using the RFLP assay. To confirm the HCV genotypes, the 5'-UTR fragment was amplified and cloned into the pJET1.2/blunt cloning vector and then sequenced. Out of 147 patients, 106 (72.1 %) were negative for anti-HCV Abs and HCV RNA. HCV RNA was found in PBMC specimens of six (5.7 %) patients, from a total of 106 patients with undetectable plasma HCV RNA and anti-HCV Abs. Therefore, six out of 106 patients had OCI. HCV genotyping revealed that three patients were infected with HCV subtype 1b, two patients were infected with HCV subtype 3a, and one patient was infected with HCV subtype 1a. These results revealed that Iranian patients with beta-thalassemia major might have OCI. Therefore, it seems that the design of a study to identify this infection in patients with β-thalassemia major would provide valuable information. PMID:27132015

  15. Metabolism and expression of RNA polymerase II transcripts in Influenza virus-infected cells

    SciTech Connect

    Katze, M.G.; Krug, R.M.

    1984-10-01

    Influenza virus infection has adverse effects on the metabolism of two representative RNA polymerase II transcripts in chicken embryo fibroblasts, those coding for BETA-actin and for avian leukosis virus (ALV) proteins. Proviral ALV DNA was integrated into host cell DNA by prior infection with ALV. By S1 endonuclease assay, it was confirmed that nuclear ALV transcripts disappeared very early after infection, already decreasing ca. 80% by 1 h postinfection. A plausible explanation for this nuclear degradation is that the viral cap-dependent endonuclease in the nucleas cleaves the 5' ends of new polymerase II transcripts, rendering the resulting decapped RNAs susceptible to hydrolysis by cellular nucleases. Similar stability of cytoplasmic host cell mRNAs was observed in infected HeLa cells, in which the levels of actin mRNA and two HeLa cell mRNAs (pHe 7 and pHe 28) remained at undiminished levels for 3 h of infection and decreased only slightly by 4.5 h postinfection. The cytoplamic actin and pHe 7 mRNAs isolated from infected HeLa cells were shown to be translated in reticulocyte extracts in biro, indicating that host mRNAs were not inactivated by a virus-induced modification. Despite the continued presence of high levels of functional host cell mRNAs, host cell protein synthesis was effectively shut off by about 3 h postinfection in both chicken embryo fibroblasts and HeLa cells. These results are consistent with the establishment of an influenza virus-specific translational system that selectively translates viral and not host mRNAs.

  16. Pathogenesis of Lassa Fever Virus Infection: I. Susceptibility of Mice to Recombinant Lassa Gp/LCMV Chimeric Virus

    PubMed Central

    Lee, Andrew M.; Cruite, Justin; Welch, Megan J.; Sullivan, Brian; Oldstone, Michael B.A.

    2013-01-01

    Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8+ T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13. PMID:23684417

  17. Pathogenesis of Lassa fever virus infection: I. Susceptibility of mice to recombinant Lassa Gp/LCMV chimeric virus.

    PubMed

    Lee, Andrew M; Cruite, Justin; Welch, Megan J; Sullivan, Brian; Oldstone, Michael B A

    2013-08-01

    Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8(+) T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13. PMID:23684417

  18. Virus infection and grazing exert counteracting influences on survivorship of native bunchgrass seedlings competing with invasive exotics

    PubMed Central

    MALMSTROM, CM; STONER, CJ; BRANDENBURG, S; NEWTON, LA

    2006-01-01

    Summary  Invasive annual grasses introduced by European settlers have largely displaced native grassland vegetation in California and now form dense stands that constrain the establishment of native perennial bunchgrass seedlings. Bunchgrass seedlings face additional pressures from both livestock grazing and barley and cereal yellow dwarf viruses (B/CYDVs), which infect both young and established grasses throughout the state.  Previous work suggested that B/CYDVs could mediate apparent competition between invasive exotic grasses and native bunchgrasses in California.  To investigate the potential significance of virus-mediated mortality for early survivorship of bunchgrass seedlings, we compared the separate and combined effects of virus infection, competition and simulated grazing in a field experiment. We infected two species of young bunchgrasses that show different sensitivity to B/CYDV infection, subjected them to competition with three different densities of exotic annuals crossed with two clipping treatments, and monitored their growth and first-year survivorship.  Although virus infection alone did not reduce first-year survivorship, it halved the survivorship of bunchgrasses competing with exotics. Within an environment in which competition strongly reduces seedling survivorship (as in natural grasslands), virus infection therefore has the power to cause additional seedling mortality and alter patterns of establishment.  Surprisingly, clipping did not reduce bunchgrass survivorship further, but rather doubled it and disproportionately increased survivorship of infected bunchgrasses.  Together with previous work, these findings show that B/CYDVs can be potentially powerful elements influencing species interactions in natural grasslands.  More generally, our findings demonstrate the potential significance of multitrophic interactions in virus ecology. Although sometimes treated collectively as plant ‘predators’, viruses and herbivores may

  19. Aryl Hydrocarbon Receptor Targets Pathways Extrinsic to Bone Marrow Cells to Enhance Neutrophil Recruitment during Influenza Virus Infection

    PubMed Central

    Teske, Sabine; Bohn, Andrea A.; Hogaboam, Jason P.; Lawrence, B. Paige

    2010-01-01

    There is growing evidence that neutrophils influence host resistance during influenza virus infection; however, factors that regulate neutrophil migration to the lung during viral infection are unclear. Activation of the aryl hydrocarbon receptor (AhR) by the pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) results in an increased number of neutrophils in the lung after influenza virus infection. The mechanism of AhR-mediated neutrophilia does not involve elevated levels of soluble neutrophil chemoattractants, upregulated adhesion molecules on pulmonary neutrophils, delayed neutrophil apoptosis, or increased vascular damage. In this study, we determined whether AhR activation increases neutrophil numbers systemically or only in the infected lung, and whether AhR-regulated events within the hematopoietic system underlie the dioxin-induced increase in pulmonary neutrophils observed during influenza virus infection. We report here that AhR activation does not increase neutrophil numbers systemically or increase neutrophil production in hematopoietic tissue, suggesting that the elevated number of neutrophils is restricted to the site of antigen challenge. The generation of CD45.2AhR−/− → CD45.1AhR+/+ bone marrow chimeric mice demonstrates that even when hematopoietic cells lack the AhR, TCDD treatment still results in twice as many pulmonary neutrophils compared with control-treated, infected CD45.2AhR−/− → CD45.1AhR+/+ chimeric mice. This finding reveals that AhR-mediated events extrinsic to bone marrow–derived cells affect the directional migration of neutrophils to the infected lung. These results suggest that the lung contains important and heretofore overlooked targets of AhR regulation, unveiling a novel mechanism for controlling neutrophil recruitment to the infected lung. PMID:18007012

  20. The Potato Virus X TGBp2 Movement Protein Associates with Endoplasmic Reticulum-Derived Vesicles during Virus Infection1

    PubMed Central

    Ju, Ho-Jong; Samuels, Timmy D.; Wang, Yuh-Shuh; Blancaflor, Elison; Payton, Mark; Mitra, Ruchira; Krishnamurthy, Konduru; Nelson, Richard S.; Verchot-Lubicz, Jeanmarie

    2005-01-01

    The green fluorescent protein (GFP) gene was fused to the potato virus X (PVX) TGBp2 gene, inserted into either the PVX infectious clone or pRTL2 plasmids, and used to study protein subcellular targeting. In protoplasts and plants inoculated with PVX-GFP:TGBp2 or transfected with pRTL2-GFP:TGBp2, fluorescence was mainly in vesicles and the endoplasmic reticulum (ER). During late stages of virus infection, fluorescence became increasingly cytosolic and nuclear. Protoplasts transfected with PVX-GFP:TGBp2 or pRTL2-GFP:TGBp2 were treated with cycloheximide and the decline of GFP fluorescence was greater in virus-infected protoplasts than in pRTL2-GFP:TGBp2-transfected protoplasts. Thus, protein instability is enhanced in virus-infected protoplasts, which may account for the cytosolic and nuclear fluorescence during late stages of infection. Immunogold labeling and electron microscopy were used to further characterize the GFP:TGBp2-induced vesicles. Label was associated with the ER and vesicles, but not the Golgi apparatus. The TGBp2-induced vesicles appeared to be ER derived. For comparison, plasmids expressing GFP fused to TGBp3 were transfected to protoplasts, bombarded to tobacco leaves, and studied in transgenic leaves. The GFP:TGBp3 proteins were associated mainly with the ER and did not cause obvious changes in the endomembrane architecture, suggesting that the vesicles reported in GFP:TGBp2 studies were induced by the PVX TGBp2 protein. In double-labeling studies using confocal microscopy, fluorescence was associated with actin filaments, but not with Golgi vesicles. We propose a model in which reorganization of the ER and increased protein degradation is linked to plasmodesmata gating. PMID:16055678

  1. NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice

    PubMed Central

    Hofstetter, Amelia R.; De La Cruz, Juan A.; Cao, Weiping; Patel, Jenish; Belser, Jessica A.; McCoy, James; Liepkalns, Justine S.; Amoah, Samuel; Cheng, Guangjie; Ranjan, Priya; Diebold, Becky A.; Shieh, Wun-Ju; Zaki, Sherif; Katz, Jacqueline M.; Sambhara, Suryaprakash; Lambeth, J. David; Gangappa, Shivaprakash

    2016-01-01

    The role of the reactive oxygen species-producing NADPH oxidase family of enzymes in the pathology of influenza A virus infection remains enigmatic. Previous reports implicated NADPH oxidase 2 in influenza A virus-induced inflammation. In contrast, NADPH oxidase 1 (Nox1) was reported to decrease inflammation in mice within 7 days post-influenza A virus infection. However, the effect of NADPH oxidase 1 on lethality and adaptive immunity after influenza A virus challenge has not been explored. Here we report improved survival and decreased morbidity in mice with catalytically inactive NADPH oxidase 1 (Nox1*/Y) compared with controls after challenge with A/PR/8/34 influenza A virus. While changes in lung inflammation were not obvious between Nox1*/Y and control mice, we observed alterations in the T cell response to influenza A virus by day 15 post-infection, including increased interleukin-7 receptor-expressing virus-specific CD8+ T cells in lungs and draining lymph nodes of Nox1*/Y, and increased cytokine-producing T cells in lungs and spleen. Furthermore, a greater percentage of conventional and interstitial dendritic cells from Nox1*/Y draining lymph nodes expressed the co-stimulatory ligand CD40 within 6 days post-infection. Results indicate that NADPH oxidase 1 modulates the innate and adaptive cellular immune response to influenza virus infection, while also playing a role in host survival. Results suggest that NADPH oxidase 1 inhibitors may be beneficial as adjunct therapeutics during acute influenza infection. PMID:26910342

  2. Efficacy, Safety, and Pharmacokinetics of Intravenous Peramivir in Children with 2009 Pandemic H1N1 Influenza A Virus Infection

    PubMed Central

    Kohno, Shigeru; Ishibashi, Toru; Wajima, Toshihiro; Takahashi, Takao

    2012-01-01

    Peramivir is a new neuraminidase inhibitor for intravenous administration that was first introduced in clinical practice in Japan. We conducted a multicenter, open-label, uncontrolled study in children with influenza virus infection ranging in age from ≥28 days to <16 years during the 2009 pandemic A (H1N1) influenza epidemic to evaluate the efficacy, safety, and pharmacokinetics of peramivir in children after intravenous infusion of 10 mg/kg (600 mg maximum) once daily. Among the 106 children (125 days to 15 years old) confirmed to have been infected with the pH1N1 virus by the PCR who were treated with peramivir, the median time to alleviation of symptoms was 29.1 h (95% confidence interval = 22.1 to 32.4), and the proportion of the 106 children who were virus positive was 78.2% on day 2 after the start of treatment and had decreased to 7.1% on day 6. The results of the safety evaluation among 117 patients enrolled in this study showed that adverse events and adverse drug reactions were reported in 62.4 and 29.1%, respectively, of the patients. All of the adverse events and adverse drug reactions resolved or improved rapidly. A population pharmacokinetic analysis was performed on the basis of 297 observed plasma concentration data obtained from 115 children with influenza virus infection. Peramivir exposure in children was within the range of levels within which the efficacy and safety was confirmed in adults, and it is considered that peramivir is clinically and virologically effective and safe in children with pH1N1 virus infection. PMID:22024821

  3. Ultrastructural Characterization and Three-Dimensional Architecture of Replication Sites in Dengue Virus-Infected Mosquito Cells

    PubMed Central

    Junjhon, Jiraphan; Pennington, Janice G.; Edwards, Thomas J.; Perera, Rushika; Lanman, Jason

    2014-01-01

    ABSTRACT During dengue virus infection of host cells, intracellular membranes are rearranged into distinct subcellular structures such as double-membrane vesicles, convoluted membranes, and tubular structures. Recent electron tomographic studies have provided a detailed three-dimensional architecture of the double-membrane vesicles, representing the sites of dengue virus replication, but temporal and spatial evidence linking membrane morphogenesis with viral RNA synthesis is lacking. Integrating techniques in electron tomography and molecular virology, we defined an early period in virus-infected mosquito cells during which the formation of a virus-modified membrane structure, the double-membrane vesicle, is proportional to the rate of viral RNA synthesis. Convoluted membranes were absent in dengue virus-infected C6/36 cells. Electron tomographic reconstructions elucidated a high-resolution view of the replication complexes inside vesicles and allowed us to identify distinct pathways of particle formation. Hence, our findings extend the structural details of dengue virus replication within mosquito cells and highlight their differences from mammalian cells. IMPORTANCE Dengue virus induces several distinct intracellular membrane structures within the endoplasmic reticulum of mammalian cells. These structures, including double-membrane vesicles and convoluted membranes, are linked, respectively, with viral replication and viral protein processing. However, dengue virus cycles between two disparate animal groups with differing physiologies: mammals and mosquitoes. Using techniques in electron microscopy, we examined the differences between intracellular structures induced by dengue virus in mosquito cells. Additionally, we utilized techniques in molecular virology to temporally link events in virus replication to the formation of these dengue virus-induced membrane structures. PMID:24522909

  4. Perfluorocarbon-mediated aeration applied to recombinant protein production by virus-infected insect cells.

    PubMed

    Gotoh; Mochizuki; Kikuchi

    2001-01-01

    Perfluorocarbon (PFC) was used as an oxygen carrier in the cultures of insect cells and virus-infected insect cells. The cell suspensions were placed on a planar layer of PFC, which was re-oxygenated in an outer aeration unit and continuously recirculated, and were agitated by two sets of impeller blades, lower one of which was set in such a way that the ridge of the blade touched the PFC layer. The maximum cell density attained in the PFC-mediated aeration culture was higher than that in surface aeration culture. On viral infection, a recombinant protein yield was significantly high in the PFC-mediated aeration culture as compared with that in the surface aeration culture, though the production was largely decreased by setting apart the lower set of the blade from the PFC-medium interface. These results showed that the PFC-mediated aeration would be a useful technique for insect cell/baculovirus expression system. Overall mass-transfer coefficient K(L) for oxygen was examined in both the PFC-mediated aeration and surface aeration systems, by using a flask whose dimensions were identical to those of spinner flasks used for the cultures. The K(L) value in the PFC-mediated system was 2.60x10(-3)cms(-1), 1.6 times higher than that in the surface aeration system, when impeller blades were positioned at PFC-medium and medium-air interfaces, respectively. However, the K(L) values in both the PFC-mediated and surface aeration systems were decreased and their differences were brought so close, as the blade was set apart from the interfaces. DO behavior in the cultures was well explained by the model calculation using the determined K(L) values and oxygen-consumption rates of viable cells. This calculation further suggested that crucial DO, under which recombinant protein productions were unsuccessful, was 0.24-0.5ppm (3-7%) in the insect cell/baculovirus expression system. PMID:11150797

  5. Activity-based ubiquitin-specific protease (USP) profiling of virus-infected and malignant human cells

    PubMed Central

    Ovaa, Huib; Kessler, Benedikt M.; Rolén, Ulrika; Galardy, Paul J.; Ploegh, Hidde L.; Masucci, Maria G.

    2004-01-01

    The family of ubiquitin (Ub)-specific proteases (USP) removes Ub from Ub conjugates and regulates a variety of cellular processes. The human genome contains many putative USP-encoding genes, but little is known about USP tissue distribution, pattern of expression, activity, and substrate specificity. We have used a chemistry-based functional proteomics approach to identify active USPs in normal, virus-infected, and tumor-derived human cells. Depending on tissue origin and stage of activation/differentiation, different USP activity profiles were revealed. The activity of specific USPs, including USP5, -7, -9, -13, -15, and -22, was up-regulated by mitogen activation or virus infection in normal T and B lymphocytes. UCH-L1 was highly expressed in tumor cell lines of epithelial and hematopoietic cell origin but was not detected in freshly isolated and mitogen-activated cells. Up-regulation of this USP was a late event in the establishment of Epstein–Barr virus-immortalized lymphoblastoid cell lines and correlated with enhanced proliferation, suggesting a possible role in growth transformation. PMID:14982996

  6. Evaluation of the Calu-3 cell line as a model of in vitro respiratory syncytial virus infection.

    PubMed

    Harcourt, Jennifer L; Caidi, Hayat; Anderson, Larry J; Haynes, Lia M

    2011-06-01

    Respiratory syncytial virus (RSV) replication is primarily limited to the upper respiratory tract epithelium and primary, differentiated normal human bronchial epithelial cells (NHBE) have, therefore, been considered a good system for in vitro analysis of lung tissue response to respiratory virus infection and virus-host interactions. However, NHBE cells are expensive, difficult to culture, and vary with the source patient. An alternate approach is to use a continuous cell line that has features of bronchial epithelial cells such as Calu-3, an epithelial cell line derived from human lung adenocarcinoma, as an in vitro model of respiratory virus infection. The results show that Calu-3 fully polarize when grown on permeable supports as liquid-covered cultures. Polarized Calu-3 are susceptible to RSV infection and release infectious virus primarily from the apical surface, consistent with studies in NHBE cells. The data demonstrate that polarized Calu-3 may serve as a useful in vitro model to study host responses to RSV infection. PMID:21458491

  7. Post-pandemic influenza A (H1N1) 2009 virus infection in pregnant women in Ceará, Brazil

    PubMed Central

    Perdigão, Anne C B; Araújo, Fernanda M C; Melo, Maria E L; Lemos, Daniele R Q; Cavalcanti, Luciano P; Ramalho, Izabel L C; Araújo, Lia C; Sousa, Deborah M; Siqueira, Marilda M; Guedes, Maria I F

    2015-01-01

    Objective The aim of this study was to present results of the post-pandemic phase of A(H1N1)pdm09 virus infection in pregnant women in Ceará, Brazil, during the January–June 2012 influenza season. Results One hundred and fifty-four nasopharyngeal swab samples were collected from pregnant women admitted to hospitals with suspected severe acute respiratory infection (SARI). Fifty-three (34·4%) had laboratory-confirmed A(H1N1)pdm09 virus infection with 15 (28·3%) outpatients and 38 (71·7%) hospitalized. Five (9·4%) women were in the first trimester of pregnancy, 20 (37·7%) in the second trimester of pregnancy, and 24 (45·2%) in the third trimester of pregnancy. Three had no information about the time of pregnancy. Six samples from newborns were also analyzed, of which three were nasopharyngeal swab positive for A(H1N1)pdm09. These swabs were collected immediately after birth, with the exception of one that was collected on the day after birth. Conclusion Our findings suggest that transplacental transfer of influenza viruses could occur as a result of severe illness in pregnancy. It is therefore important to encourage women to be vaccinated against influenza in order to avoid pregnancy complications. PMID:26290133

  8. Role of neutralizing antibodies and T-cells in pathogenesis of herpes simplex virus infection in congenitally athymic mice.

    PubMed

    Kapoor, A K; Buckmaster, A; Nash, A A; Field, H J; Wildy, P

    1982-11-01

    Congenitally athymic nude mice were infected with 10(4) p.f.u. herpes simplex type 1 (strain SC16). Following the passive transfer of neutralizing monoclonal antibodies (AP7, AP8 and AP12) it was observed that AP7 alone reduced the virus infectivity in the nervous system; AP8 and AP12 failed to protect mice probably due to poor in vivo binding to the neutralization site on the virus. Latent ganglionic infection could be established in nude mice following adoptive transfer of optimum number (2 x 10(7) cells/mouse) of immune lymph node cells from day 7 herpes virus-infected hairy immunocompetent donor mice. Moreover, in some of the immune lymph node cell protected nudes, latency could be maintained even in complete absence of neutralizing antibodies. Results of ear-ablation experiments revealed that removal of primary source of infection after day 5 of infection reduced the amount of virus in the ganglia and spinal cord. Acute neurological infection was not detected following transfer of protective anti-gp-D neutralizing antibody (LP2) in combination with removal of infected pinna. These data suggest that continuous seeding of virus occurs in related ganglia via the axonal route from infected ear pinna. It appears that local T-cell-mediated immune mechanisms are involved in maintenance of latency. PMID:6984425

  9. Development of a Colloidal Gold Kit for the Diagnosis of Severe Fever with Thrombocytopenia Syndrome Virus Infection

    PubMed Central

    Wang, Xianguo; Zhang, Quanfu; Hao, Fen; Gao, Xunian; Wu, Wei; Liang, Minyao; Liao, Zhihua; Xu, Weiwen; Li, Dexin; Wang, Shiwen

    2014-01-01

    It is critical to develop a cost-effective detection kit for rapid diagnosis and on-site detection of severe fever with thrombocytopenia syndrome virus (SFTSV) infection. Here, an immunochromatographic assay (ICA) to detect SFTSV infection is described. The ICA uses gold nanoparticles coated with recombinant SFTSV for the simultaneous detection of IgG and IgM antibodies to SFTSV. The ICA was developed and evaluated by using positive sera samples of SFTSV infection (n = 245) collected from the CDC of China. The reference laboratory diagnosis of SFTSV infection was based on the “gold standard”. The results demonstrated that the positive coincidence rate and negative coincidence rate were determined to be 98.4% and 100% for IgM and 96.7% and 98.6% for IgG, respectively. The kit showed good selectivity for detection of SFTSV-specific IgG and IgM with no interference from positive sera samples of Japanese encephalitis virus infection, Dengue virus infection, Hantavirus infection, HIV infection, HBV surface antigen, HCV antibody, Mycobacterium tuberculosis antibody, or RF. Based on these results, the ICS test developed may be a suitable tool for rapid on-site testing for SFTSV infections. PMID:24826381

  10. Identification of novel cellular targets for therapeutic intervention against Ebola virus infection by siRNA screening.

    PubMed

    Kolokoltsov, Andrey A; Saeed, Mohammad F; Freiberg, Alexander N; Holbrook, Michael R; Davey, Robert A

    2009-06-01

    While much progress has been made in developing drugs against a few prominent viruses such as HIV, few examples exist for emerging infectious agents. In some cases broad spectrum anti-viral drugs, such as ribavirin, are effective, but for some groups of viruses, these show little efficacy in animal models. Traditional methods focus on screening small molecule libraries to identify drugs that target virus factors, with the intention that side-effects to the host can be minimized. However, this greatly limits potential drug targets and virus genes can rapidly mutate to avoid drug action. Recent advances in siRNA gene targeting technologies have provided a powerful tool to specifically target and suppress the expression of cell genes. Since viruses are completely dependent upon host cell proteins for propagation, siRNA screening promises to reveal novel cell proteins and signaling pathways that may be viable targets for drug therapy regimens. Here we used an siRNA screening approach to identify gene products that play critical roles in Ebola virus infection. By gene cluster analysis, proteins in phosphatidylinositol-3-kinase and calcium/calmodulin kinase related networks were identified as important for Zaire Ebola virus infection and prioritized for further evaluation. Key roles of each were confirmed by testing available drugs specific for members of each pathway. Interestingly, both sets of proteins are also important in cancer and subject to intense investigation. Thus development of new drugs against these cancer targets may also prove useful in combating Ebola virus. PMID:20930947

  11. Whole genome sequencing to identify host genetic risk factors for severe outcomes of hepatitis A virus infection

    PubMed Central

    Long, Dustin; Fix, Oren K.; Deng, Xutao; Seielstad, Mark; Lauring, Adam S.

    2014-01-01

    Acute liver failure is a severe, but rare, outcome of hepatitis A virus infection. Unusual presentations of prevalent infections have often been attributed to pathogen-specific immune deficits that exhibit Mendelian inheritance. Genome-wide resequencing of unrelated cases has proven to be a powerful approach for identifying highly penetrant risk alleles that underlie such syndromes. Rare mutations likely to affect protein expression or function can be identified from sequence data, and their association with a similarly rare phenotype rests on their existence in multiple affected individuals. A rare or novel sequence variant that is enriched to a significant degree in a genetically diverse cohort suggests a candidate susceptibility allele. Whole genome sequencing of ten individuals from ethnically diverse backgrounds with HAV-associated acute liver failure was performed. A set of rational filtering criteria was used to identify genetic variants that are rare in the population, but enriched in this cohort. Single nucleotide polymorphisms, insertions, and deletions were considered and autosomal dominant, autosomal recessive, and polygenic models were applied. Analysis of the protein-coding exome identified no single gene with putatively deleterious mutations shared by multiple individuals, arguing against a simple Mendelian model of inheritance. A number of rare variants were significantly enriched in this cohort, consistent with a complex and genetically heterogeneous trait. Several of the variants identified in this genome-wide study lie within genes important to hepatic pathophysiology and are candidate susceptibility alleles for hepatitis A virus infection. PMID:24978929

  12. Evaluation of a commercial dengue NS1 antigen-capture ELISA for laboratory diagnosis of acute dengue virus infection.

    PubMed

    Kumarasamy, V; Wahab, A H Abdul; Chua, S K; Hassan, Z; Chem, Y K; Mohamad, M; Chua, K B

    2007-03-01

    A commercial dengue NS1 antigen-capture ELISA was evaluated to demonstrate its potential application for early laboratory diagnosis of acute dengue virus infection. Dengue virus NS1 antigen was detected in 199 of 213 acute serum samples from patients with laboratory confirmation of acute dengue virus infection but none of the 354 healthy blood donors' serum specimens. The dengue NS1 antigen-capture ELISA gave an overall sensitivity of 93.4% (199/213) and a specificity of 100% (354/354). The sensitivity was significantly higher in acute primary dengue (97.3%) than in acute secondary dengue (70.0%). The positive predictive value of the dengue NS1 antigen-capture ELISA was 100% and negative predictive value was 97.3%. Comparatively, virus isolation gave an overall positive isolation rate of 68.1% with a positive isolation rate of 73.9 and 31.0% for acute primary dengue and acute secondary dengue, respectively. Molecular detection of dengue RNA by RT-PCR gave an overall positive detection rate of 66.7% with a detection rate of 65.2 and 75.9% for acute primary dengue and acute secondary dengue, respectively. The results indicate that the commercial dengue NS1 antigen-capture ELISA may be superior to virus isolation and RT-PCR for the laboratory diagnosis of acute dengue infection based on a single serum sample. PMID:17140671

  13. Type III interferon gene expression in response to influenza virus infection in chicken and duck embryonic fibroblasts.

    PubMed

    Zhang, Zhijie; Zou, Tingting; Hu, Xiaotong; Jin, Hong

    2015-12-01

    Type III interferons (IFN-λs) comprise a group of newly identified antiviral cytokines that are functionally similar to type I IFNs and elicit first-line antiviral responses. Recently, type III IFNs were identified in several species; however, little information is available about type III IFNs in ducks. We compared the expression of type III IFNs and their receptor in chicken embryonic fibroblasts (CEFs) and duck embryonic fibroblasts (DEFs) in response to influenza virus infection. The results showed that the expression of type III IFNs was upregulated in both DEFs and CEFs following infection with H1N1 influenza virus or treatment with poly (I:C), and expression levels were significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs (IL-28Rα) was also upregulated following infection with H1N1 virus or treatment with poly (I:C) and was significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs occurred from 8 hpi and remained at similar levels until 36 hpi in CEFs, but the expression level was elevated from 36 hpi in DEFs. These findings revealed the existence of distinct expression patterns for type III IFNs in chickens and ducks in response to influenza virus infection. The provided data are fundamentally useful in furthering our understanding of type III IFNs and innate antiviral responses in different species. PMID:26598110

  14. Oseltamivir-resistant pandemic (H1N1) 2009 virus infection in England and Scotland, 2009-2010.

    PubMed

    Calatayud, Laurence; Lackenby, Angie; Reynolds, Arlene; McMenamin, Jim; Phin, Nick F; Zambon, Maria; Pebody, Richard

    2011-10-01

    Oseltamivir has been widely used for pandemic (H1N1) 2009 virus infection, and by April 30, 2010, a total of 285 resistant cases were reported worldwide, including 45 in the United Kingdom. To determine risk factors for emergence of oseltamivir resistance and severe infection, a case-control study was conducted in the United Kingdom. Study participants were hospitalized in England or Scotland during January 4, 2009-April 30, 2010. Controls had confirmed oseltamivir-sensitive pandemic (H1N1) 2009 virus infections, and case-patients had confirmed oseltamivir-resistant infections. Of 28 case-patients with available information, 21 (75%) were immunocompromised; 31 of 33 case-patients (94%) received antiviral drugs before a sample was obtained. After adjusting for confounders, case-patients remained significantly more likely than controls to be immunocompromised and at higher risk for showing development of respiratory complications. Selective drug pressure likely explains the development of oseltamivir resistance, especially among immunocompromised patients. Monitoring of antiviral resistance is strongly recommended in this group. PMID:22000349

  15. Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus Infection in England and Scotland, 2009–2010

    PubMed Central

    Lackenby, Angie; Reynolds, Arlene; McMenamin, Jim; Phin, Nick F.; Zambon, Maria C.; Pebody, Richard

    2011-01-01

    Oseltamivir has been widely used for pandemic (H1N1) 2009 virus infection, and by April 30, 2010, a total of 285 resistant cases were reported worldwide, including 45 in the United Kingdom. To determine risk factors for emergence of oseltamivir resistance and severe infection, a case–control study was conducted in the United Kingdom. Study participants were hospitalized in England or Scotland during January 4, 2009–April 30, 2010. Controls had confirmed oseltamivir-sensitive pandemic (H1N1) 2009 virus infections, and case-patients had confirmed oseltamivir-resistant infections. Of 28 case-patients with available information, 21 (75%) were immunocompromised; 31 of 33 case-patients (94%) received antiviral drugs before a sample was obtained. After adjusting for confounders, case-patients remained significantly more likely than controls to be immunocompromised and at higher risk for showing development of respiratory complications. Selective drug pressure likely explains the development of oseltamivir resistance, especially among immunocompromised patients. Monitoring of antiviral resistance is strongly recommended in this group. PMID:22000349

  16. Combination ledipasvir-sofosbuvir for the treatment of chronic hepatitis C virus infection: a review and clinical perspective.

    PubMed

    Nkuize, Marcel; Sersté, Thomas; Buset, Michel; Mulkay, Jean-Pierre

    2016-01-01

    Chronic hepatitis C treatment has continued to evolve, and interferon-free, oral treatment with direct-acting antiviral agents is the current standard of care. Recently, a new treatment, which is a combination of two direct-acting antiviral agents, ledipasvir 90 mg (anti-NS5A) and sofosbuvir 400 mg (anti-NS5B), has been approved in the US and the European Union for the treatment of chronic hepatitis C viral infection. In Phase III trials among chronic hepatitis C virus genotype 1 monoinfected (treatment-naïve, treatment-experienced, and with advanced liver disease or posttransplant) patients and HIV-hepatitis C virus coinfected patients, the ledipasvir-sofosbuvir fixed-dose combination is associated with a higher rate of sustained virologic response at 12 weeks after therapy has ceased. According to preliminary data, the ledipasvir-sofosbuvir combination also may be effective against hepatitis C genotype 4 virus infection. The ledipasvir-sofosbuvir combination taken orally is generally well-tolerated. Moreover, the combination treatment may suppress the effect of predictive factors of chronic hepatitis C that have historically been known to be associated with treatment failure. Thus, the fixed-dose single-tablet combination of ledipasvir-sofosbuvir offers a new era for the effective treatment of a variety of patients suffering from chronic hepatitis C virus infection. PMID:27350749

  17. Combination ledipasvir-sofosbuvir for the treatment of chronic hepatitis C virus infection: a review and clinical perspective

    PubMed Central

    Nkuize, Marcel; Sersté, Thomas; Buset, Michel; Mulkay, Jean-Pierre

    2016-01-01

    Chronic hepatitis C treatment has continued to evolve, and interferon-free, oral treatment with direct-acting antiviral agents is the current standard of care. Recently, a new treatment, which is a combination of two direct-acting antiviral agents, ledipasvir 90 mg (anti-NS5A) and sofosbuvir 400 mg (anti-NS5B), has been approved in the US and the European Union for the treatment of chronic hepatitis C viral infection. In Phase III trials among chronic hepatitis C virus genotype 1 monoinfected (treatment-naïve, treatment-experienced, and with advanced liver disease or posttransplant) patients and HIV–hepatitis C virus coinfected patients, the ledipasvir-sofosbuvir fixed-dose combination is associated with a higher rate of sustained virologic response at 12 weeks after therapy has ceased. According to preliminary data, the ledipasvir-sofosbuvir combination also may be effective against hepatitis C genotype 4 virus infection. The ledipasvir-sofosbuvir combination taken orally is generally well-tolerated. Moreover, the combination treatment may suppress the effect of predictive factors of chronic hepatitis C that have historically been known to be associated with treatment failure. Thus, the fixed-dose single-tablet combination of ledipasvir-sofosbuvir offers a new era for the effective treatment of a variety of patients suffering from chronic hepatitis C virus infection. PMID:27350749

  18. Application of speckle image correlation for real-time assessment of metabolic activity in herpes virus-infected cells

    NASA Astrophysics Data System (ADS)

    Vladimirov, A. P.; Malygin, A. S.; Mikhailova, J. A.; Borodin, E. M.; Bakharev, A. A.; Poryvayeva, A. P.

    2014-09-01

    Earlier we reported developing a speckle interferometry technique and a device designed to assess the metabolic activity of a cell monolayer cultivated on a glass substrate. This paper aimed at upgrading the technique and studying its potential for real-time assessment of herpes virus development process. Speckle dynamics was recorded in the image plane of intact and virus-infected cell monolayer. HLE-3, L-41 and Vero cells were chosen as research targets. Herpes simplex virus-1-(HSV-1)- infected cell cultures were studied. For 24 h we recorded the digital value of optical signal I in one pixel and parameter η characterizing change in the distribution of the optical signal on 10 × 10-pixel areas. The coefficient of multiple determination calculated by η time dependences for three intact cell cultures equals 0.94. It was demonstrated that the activity parameters are significantly different for intact and virus-infected cells. The difference of η value for intact and HSV-1-infected cells is detectable 10 minutes from the experiment start.

  19. Protection Against H7 Subtype Influenza Virus Infection in Mice by Passive Transfer of Neutralizing Monoclonal Antibody.

    PubMed

    Zhang, Zhuo; Liu, Ming; Zheng, Shimin

    2015-10-01

    H7 subtype influenza viruses pose serious threats to both the poultry industry and public health. Recent human infections of avian H7N9 influenza viruses with substantial morbidity and mortality have raised concerns about this virus becoming a potential pandemic pathogen. Neutralizing antibodies have been proven to be highly effective in blocking influenza virus infections. In this study, in order to develop an antibody-based immunoprophylaxis against H7 subtype influenza virus, we first generated a neutralizing monoclonal antibody (MAb) by using a pseudotyped lentiviral vector carrying the hemagglutinin protein of H7 subtype influenza virus. In vitro studies demonstrated that this neutralizing MAb completely inhibited the infection of an H7 subtype influenza virus to cells. The protective efficacy of this MAb was then further tested in a mouse model. It was shown that passive immunization of this MAb protected mice from local virus challenge. Results of the current study lay a foundation for the development of neutralizing MAb-mediated prophylactic strategies to combat human H7 influenza virus infections. PMID:26492625

  20. Envelope Glycoprotein Internalization Protects Human and Simian Immunodeficiency Virus-Infected Cells from Antibody-Dependent Cell-Mediated Cytotoxicity

    PubMed Central

    von Bredow, Benjamin; Arias, Juan F.; Heyer, Lisa N.; Gardner, Matthew R.; Farzan, Michael; Rakasz, Eva G.

    2015-01-01

    ABSTRACT The cytoplasmic tails of human and simian immunodeficiency virus (HIV and SIV, respectively) envelope glycoproteins contain a highly conserved, membrane-proximal endocytosis motif that prevents the accumulation of Env on the surface of infected cells prior to virus assembly. Using an assay designed to measure the killing of virus-infected cells by antibody-dependent cell-mediated cytotoxicity (ADCC), we show that substitutions in this motif increase the susceptibility of HIV-1- and SIV-infected cells to ADCC in a manner that directly correlates with elevated Env levels on the surface of virus-infected cells. In the case of HIV-1, this effect is additive with a deletion in vpu recently shown to enhance the susceptibility of HIV-1-infected cells to ADCC as a result of tetherin-mediated retention of budding virions on the cell surface. These results reveal a previously unappreciated role for the membrane-proximal endocytosis motif of gp41 in protecting HIV-1- and SIV-infected cells from antibody responses by regulating the amount of Env present on the cell surface. IMPORTANCE This study reveals an unappreciated role for the membrane-proximal endocytosis motif of gp41 in protecting HIV-1- and SIV-infected cells from elimination by Env-specific antibodies. Thus, strategies designed to interfere with this mechanism of Env internalization may improve the efficacy of antibody-based vaccines and antiretroviral therapies designed to enhance the immunological control of HIV-1 replication in chronically infected individuals. PMID:26269175

  1. Effects of Soluble CD4 on Simian Immunodeficiency Virus Infection of CD4-Positive and CD4-Negative Cells

    PubMed Central

    Schenten, Dominik; Marcon, Luisa; Karlsson, Gunilla B.; Parolin, Cristina; Kodama, Toshiaki; Gerard, Norma; Sodroski, Joseph

    1999-01-01

    A soluble form of the CD4 receptor (sCD4) can either enhance or inhibit the infection of cells by simian immunodeficiency virus (SIV) and human immunodeficiency virus. We investigated the basis for these varying effects by studying the entry of three SIV isolates into CD4-positive and CD4-negative cells expressing different chemokine receptors. Infection of CD4-negative cells depended upon the viral envelope glycoproteins and upon the chemokine receptor, with CCR5 and gpr15 being more efficient than STRL33. Likewise, enhancement of infection by sCD4 was observed when CCR5- and gpr15-expressing target cells were used but not when those expressing STRL33 were used. The sCD4-mediated enhancement of virus infection of CD4-negative, CCR5-positive cells was related to the sCD4-induced increase in binding of the viral gp120 envelope glycoprotein to CCR5. Inhibitory effects of sCD4 could largely be explained by competition for virus attachment to cellular CD4 rather than other detrimental effects on virus infectivity (e.g., disruption of the envelope glycoprotein spike). Consistent with this, the sCD4-activated SIV envelope glycoprotein intermediate on the virus was long-lived. Thus, the net effect of sCD4 on SIV infectivity appears to depend upon the degree of enhancement of chemokine receptor binding and upon the efficiency of competition for cellular CD4. PMID:10364284

  2. Vesicular stomatitis virus infects resident cells of the central nervous system and induces replication-dependent inflammatory responses

    SciTech Connect

    Chauhan, Vinita S.; Furr, Samantha R.; Sterka, David G.; Nelson, Daniel A.; Moerdyk-Schauwecker, Megan; Marriott, Ian; Grdzelishvili, Valery Z.

    2010-05-10

    Vesicular stomatitis virus (VSV) infection of mice via intranasal administration results in a severe encephalitis with rapid activation and proliferation of microglia and astrocytes. We have recently shown that these glial cells express RIG-I and MDA5, cytosolic pattern recognition receptors for viral RNA. However, it is unclear whether VSV can replicate in glial cells or if such replication is required for their inflammatory responses. Here we demonstrate that primary microglia and astrocytes are permissive for VSV infection and limited productive replication. Importantly, we show that viral replication is required for robust inflammatory mediator production by these cells. Finally, we have confirmed that in vivo VSV administration can result in viral infection of glial cells in situ. These results suggest that viral replication within resident glial cells might play an important role in CNS inflammation following infection with VSV and possibly other neurotropic nonsegmented negative-strand RNA viruses.

  3. Travelers With Chikungunya Virus Infection Returning to Northwest Italy From the Caribbean and Central America During June-November 2014.

    PubMed

    Burdino, Elisa; Ruggiero, Tina; Milia, Maria Grazia; Proietti, Alex; Sergi, Giuseppina; Torta, Ilaria; Calleri, Guido; Caramello, Pietro; Tiberti, Donatella; Ghisetti, Valeria

    2015-01-01

    Chikungunya virus (CHIKV) has recently emerged in the Caribbean. In Italy, CHIKV vector is documented in the Po river valley; therefore, a risk for autochthonous outbreaks is present. We report a case series of seven imported CHIKV infections in travelers returning from the Caribbean and Latin America occurring between June and November 2014, in the area of Turin, Northwest Italy, 3 years after the last imported cases were reported. These cases are a reminder of the need to always consider CHIKV infection in travelers from these epidemic areas as well as the importance of a prompt diagnosis. PMID:26080943

  4. Relationship between hepatitis C virus infection and type 2 diabetes mellitus: Meta-analysis

    PubMed Central

    Naing, Cho; Mak, Joon Wah; Ahmed, Syed Imran; Maung, Mala

    2012-01-01

    AIM: To investigate the association between hepatitis C infection and type 2 diabetes mellitus. METHODS: Observational studies assessing the relationship between hepatitis C infection and type 2 diabetes mellitus were identified via electronic and hand searches. Studies published between 1988 to March 2011 were screened, according to the inclusion criteria set for the present analysis. Authors performed separate analyses for the comparisons between hepatitis C virus (HCV) infected and not infected, and HCV infected and hepatitis B virus infected. The included studies were further subgrouped according to the study design. Heterogenity was assessed using I2 statistics. The summary odds ratios with their corresponding 95% CIs were calculated based on a random-effects model. The included studies were subgrouped according to the study design. To assess any factor that could potentially affect the outcome, results were further stratified by age group (proportion of ≥ 40 years), gender (proportion of male gender), body mass index (BMI) (proportion of BMI ≥ 27), and family history of diabetes (i.e., self reported). For stability of results, a sensitivity analysis was conducted including only prospective studies. RESULTS: Combining the electronic database and hand searches, a total of 35 observational studies (in 31 articles) were identified for the final analysis. Based on random-effects model, 17 studies (n = 286 084) compared hepatitis C-infected patients with those who were uninfected [summary odds ratio (OR): 1.68, 95% CI: 1.15-2.45]. Of these 17 studies, 7 were both a cross-sectional design (41.2%) and cohort design (41.2%), while 3 were case-control studies (17.6%). Nineteen studies (n = 51 156) compared hepatitis C-infected participants with hepatitis B-infected (summary OR: 1.92, 95% CI: 1.41-2.62). Of these 19 studies, 4 (21.1%), 6 (31.6%) and 9 (47.4%) were cross-sectional, cohort and case-control studies, respectively. A sensitivity analysis with 3

  5. Influence of the simulated microgravity on biomass and contents of carbohydrates at virus-infected wheat plants

    NASA Astrophysics Data System (ADS)

    Mishchenko, L.; Silayeva, A.; Mishchenko, I.; Boyko, A.

    The effects of clinostating has been studied on the contents of biomass, soluble carbohydrates and starches in Wheat streak mosaic virus (WSMV) infected plants of wheat Donska semidwarf, Albatross Odessky, Kollectivna-3 (summer), and Apogee (early-ripe, superdwarf). Plants in conditions of horizontal and vertical rotation with a frequency 2 min-1 were grown in containers during 35 days. WSMV was accumulated on barley i dicator plants of Ros' variety for then subsequent infestation by this virus of a part of clinostating and motionless wheat plants in a stage of 3 leaves. Researches have shown, that the most suitable for ground experiments with clinostating were Kollectivna-3 and Apogee varieties. At vertical and horizontal rotation of wheat plants of Kollectivna - 3 variety the weight of roots increased and that of above-ground part (leaves and stalks) decreased in comparison with motionless control plants, that resulted in decrease of the ratio of a biomass of an above-ground part to a root system. In Apogee variety the weight of the above-ground part of healthy plants at vertical clinostating decreased by 23 % in comparison with motionless variant, and the biomass of virus-infected plants was reduced on the average by 14 % in comparison with infected motionless control. The weight of above-ground part of infected and healthy motionless plants practically did not differ. Vertical clinorotation of plants caused the reduction of ear weight while in horizontally rotated plants and in the motionless control there were no difference. The number of ears in Apogee variety practically did not change in all variants of the experiment, and plant weight at clinostating decreased in both healthy, and virus infected plants. For the period of cultivation in Kollectivna-3 variety ears were not formed at all. The contents of soluble carbohydrates (reducing and saccharose) in leaves and stalks of healthy and virus infected at clinostating was increased in Apogee in 1,6-2,2 times

  6. Prevalence, socio-demographic features and risk factors of Hepatitis B virus infection among pregnant women in Southwestern Nigeria

    PubMed Central

    Anaedobe, Chinenye Gloria; Fowotade, Adeola; Omoruyi, Chukwuma Ewean; Bakare, Rasheed Ajani

    2015-01-01

    Introduction Hepatitis B virus is responsible for 50%-80% of Hepatocellular carcinoma cases worldwide. In Nigeria, vertical transmission remains a major route of Hepatitis B virus infection. Primary (vaccines and post-exposure prophylaxis) and secondary prevention of HBV transmission by appropriate sexual and sanitary practices are not yet optimal in the country yet measures for early detection (serological, molecular) and treatment of infected pregnant women is not a practice. This study aimed at identifying the prevalence and risk factors for Hepatitis B virus infection among pregnant women in Ibadan, Southwestern Nigeria. Methods A cross-sectional study was done at the Ante-natal clinic of the University College Hospital Ibadan. One hundred and eighty pregnant women were recruited from March to August 2013, and tested for Hepatitis B surface antigen (BIORAD FRANCE) using third generation ELISA, as well as HIV-1 and 2 using Uni-Gold Recombigen and ALERE determine (a rapid immunoassay designed to detect antibodies to HIV 1 and/or 2). Positive HBsAg samples were tested for Hepatitis B envelope antigen, antibody and Hepatitis B core antibody (DIAPRO Italy) while serum HBV DNA was detected using PCR. Data were obtained using questionnaires to establish and analysis was performed using SPSS version 20. Results The seroprevalence of HBsAg was 8.3% out of which 26.7% were positive for HBeAg, 53.3% had HBeAb, 20% had neither HBeAg nor HBeAb, 100% had total HBcAb and 86.7% had HBV DNA in their serum. The mean age was 32.1years, the highest HBV infection rate occurred in 25-29 year age group. Multiple sexual partners (OR- 3.987, P- value=0.026) and early age at sexual debut (OR 11.996, P- value=0.022) were independent risk factors for HBV infection. Conclusion Hepatitis B virus infection is of high endemicity in Nigeria thus early detection, treatment of infected pregnant women, immunoprophylaxis for exposed newborns and surveillance for those with chronic infection is

  7. The 474-Kilobase-Pair Complete Genome Sequence of CeV-01B, a Virus Infecting Haptolina (Chrysochromulina) ericina (Prymnesiophyceae)

    PubMed Central

    Gallot-Lavallée, Lucie; Pagarete, António; Legendre, Matthieu; Santini, Sebastien; Sandaa, Ruth-Anne; Himmelbauer, Heinz; Ogata, Hiroyuki; Bratbak, Gunnar

    2015-01-01

    We report the complete genome sequence of CeV-01B, a large double-stranded DNA virus infecting the unicellular marine phytoplankton Haptolina (formerly Chrysochromulina) ericina. CeV-01B and its closest relative Phaeocystis globosa virus define an emerging subclade of the Megaviridae family with smaller genomes and particles than the originally described giant Mimiviridae infecting Acanthamoeba. PMID:26634761

  8. Influenza A Virus Infection of Intestinal Epithelial Cells Enhances the Adhesion Ability of Crohn’s Disease Associated Escherichia coli Strains

    PubMed Central

    Aleandri, Marta; Conte, Maria Pia; Simonetti, Giovanna; Panella, Simona; Celestino, Ignacio; Checconi, Paola; Marazzato, Massimiliano; Longhi, Catia; Goldoni, Paola; Nicoletti, Mauro; Barnich, Nicolas; Palamara, Anna Teresa; Schippa, Serena; Nencioni, Lucia

    2015-01-01

    Modifications of intestinal glycoreceptors expression, in particular CEACAM6, typically found in ileal Crohn's disease (CD), favor, among the commensal species of microbiota, the enrichment in Escherichia coli. Removal of protein glycosidic residues by neuraminidase, a sialidase typical of influenza virus, increases adhesion ability of Escherichia coli to Caco-2 intestinal cells. In this study we investigated whether influenza virus infection of human intestinal epithelial cells could influence the adhesiveness of different Escherichia coli strains isolated from CD patients by altering surface glycoreceptors. Influenza virus infection of intestinal cells increased exposure of galactose and mannose residues on the cell surface. In particular, glycoreceptors Thomsen-Friedenreich and CEACAM6 were over-expressed in influenza virus infected cells. In the same experimental conditions, a significant increase in bacterial adhesiveness was observed, independently of their own adhesive ability. The increase was reverted by treatment with anti-TF and anti-CEACAM6 antibodies. Interestingly, influenza virus was able to efficiently replicate in human primary intestinal cells leading to TF exposure. Finally, intestinal infected cells produced high levels of pro-inflammatory cytokines compared to control. Overall these data suggest that influenza virus infection, could constitute an additional risk factor in CD patients. PMID:25706391

  9. Frequency of hepatitis B, C and D and human immunodeficiency virus infections in multi-transfused thalassemics.

    PubMed

    Amarapurkar, D N; Kumar, A; Vaidya, S; Murti, P; Bichile, S K; Kalro, R H; Desai, H G

    1992-04-01

    Of forty multi-transfused thalassemia patients (26 males, 14 females; mean age 8.1 +/- 5.3 years, range 1-35) with no clinical or biochemical evidence of liver disease, HBsAg, anti-hepatitis C virus and anti-human immunodeficiency virus antibodies were present in 18 (45%), 7 (17.5%) and 1 (2.5%) cases respectively. Three of the 18 (16.7%) HBsAg positive patients were anti-delta antibody positive. Our results indicate that more than 50% of multi-transfused thalassemia patients show serological evidence of one or more of hepatitis B, C and D and human immunodeficiency virus infection. PMID:1428037

  10. Complement-Dependent Lysis of Influenza A Virus-Infected Cells by Broadly Cross-Reactive Human Monoclonal Antibodies ▿

    PubMed Central

    Terajima, Masanori; Cruz, John; Co, Mary Dawn T.; Lee, Jane-Hwei; Kaur, Kaval; Wilson, Patrick C.; Ennis, Francis A.

    2011-01-01

    We characterized human monoclonal antibodies (MAbs) cloned from influenza virus-infected patients and from influenza vaccine recipients by complement-dependent lysis (CDL) assay. Most MAbs active in CDL were neutralizing, but not all neutralizing MAbs can mediate CDL. Two of the three stalk-specific neutralizing MAbs tested were able to mediate CDL and were more cross-reactive to temporally distant H1N1 strains than the conventional hemagglutination-inhibiting and neutralizing MAbs. One of the stalk-specific MAbs was subtype cross-reactive to H1 and H2 hemagglutinins, suggesting a role for stalk-specific antibodies in protection against influenza illness, especially by a novel viral subtype which can cause pandemics. PMID:21994454

  11. Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment

    PubMed Central

    Pastore, Francesca; Martocchia, Antonio; Stefanelli, Manuela; Prunas, Pietro; Giordano, Stefania; Toussan, Lavinia; Devito, Antonio; Falaschi, Paolo

    2016-01-01

    The hepatitis C virus (HCV) infection is an important public health problem and it is associated with hepatic and extrahepatic manifestations. Autoimmune thyroid diseases are common in HCV infected patients and the standard interferon-based treatment is associated with an increase of the immune-mediated thyroid damage. Recent evidence in the literature analyzed critical points of the mechanisms of thyroid damage, focusing on the balance between the two sides of the interaction: The environment (virus infection with potential cross-reaction) and the host (susceptibility genes with consistent immune response). The spectrum of antiviral treatment for chronic HCV infection is rapidly expanding for the development of dual o triple therapy. The availability of interferon-free combined treatment with direct antiviral agents for HCV is very promising, in order to ameliorate the patient compliance and to reduce the development of thyroid autoimmunity. PMID:26807204

  12. Fatal H5N6 Avian Influenza Virus Infection in a Domestic Cat and Wild Birds in China

    PubMed Central

    Yu, Zhijun; Gao, Xiaolong; Wang, Tiecheng; Li, Yanbing; Li, Yongcheng; Xu, Yu; Chu, Dong; Sun, Heting; Wu, Changjiang; Li, Shengnan; Wang, Haijun; Li, Yuanguo; Xia, Zhiping; Lin, Weishi; Qian, Jun; Chen, Hualan; Xia, Xianzhu; Gao, Yuwei

    2015-01-01

    H5N6 avian influenza viruses (AIVs) may pose a potential human risk as suggested by the first documented naturally-acquired human H5N6 virus infection in 2014. Here, we report the first cases of fatal H5N6 avian influenza virus (AIV) infection in a domestic cat and wild birds. These cases followed human H5N6 infections in China and preceded an H5N6 outbreak in chickens. The extensive migration routes of wild birds may contribute to the geographic spread of H5N6 AIVs and pose a risk to humans and susceptible domesticated animals, and the H5N6 AIVs may spread from southern China to northern China by wild birds. Additional surveillance is required to better understand the threat of zoonotic transmission of AIVs. PMID:26034886

  13. Metabolomic plasticity in GM and non-GM potato leaves in response to aphid herbivory and virus infection.

    PubMed

    Plischke, Andreas; Choi, Young Hae; Brakefield, Paul M; Klinkhamer, Peter G L; Bruinsma, Maaike

    2012-02-15

    An important aspect of ecological safety of genetically modified (GM) plants is the evaluation of unintended effects on plant-insect interactions. These interactions are to a large extent influenced by the chemical composition of plants. This study uses NMR-based metabolomics to establish a baseline of chemical variation to which differences between a GM potato line and its parent cultivar are compared. The effects of leaf age, virus infection, and aphid herbivory on plant metabolomes were studied. The metabolome of the GM line differed from its parent only in young leaves of noninfected plants. This effect was small when compared to the baseline. Consistently, aphid performance on excised leaves was influenced by leaf age, while no difference in performance was found between GM and non-GM plants. The metabolomic baseline approach is concluded to be a useful tool in ecological safety assessment. PMID:22243672

  14. Anchoring a secreted plasmodium antigen on the surface of recombinant vaccinia virus-infected cells increases its immunogenicity.

    PubMed Central

    Langford, C J; Edwards, S J; Smith, G L; Mitchell, G F; Moss, B; Kemp, D J; Anders, R F

    1986-01-01

    We show that the subcellular location of foreign antigens expressed in recombinant vaccinia viruses influences their effectiveness as immunogens. Live recombinant viruses induced very poor antibody responses to a secreted repetitive plasmodial antigen (the S-antigen) in rabbits and mice. The poor response accords with epidemiological data suggesting that S-antigens are poorly immunogenic. Appending the transmembrane domain of a membrane immunoglobulin (immunoglobulin G1) to its carboxy terminus produced a hybrid S-antigen that was no longer secreted but was located on the surface of virus-infected cells. This recombinant virus elicited high antibody titers to the S-antigen. This approach will facilitate the use of live virus delivery systems to immunize against a wide range of foreign nonsurface antigens. Images PMID:3537732

  15. Natural A(H1N1)pdm09 influenza virus infection case in a pet ferret in Taiwan.

    PubMed

    Lin, Hui-Ting; Wang, Ching-Ho; Wu, Wen-Ling; Chi, Chau-Hwa; Wang, Lih Chiann

    2014-11-01

    Ferrets have demonstrated high susceptibility to the influenza virus. This study discusses a natural 2009 pandemic influenza A (H1N1) (A(H1N1)pdm09) virus infection in a pet ferret (Mustela putorius furo) identified in Taiwan in 2013. The ferret was in close contact with family members who had recently experienced an influenza-like illness (ILI). The ferret nasal swab showed positive results for influenza A virus using one-step RT-PCR. The virus was isolated and the phylogenetic analysis indicated that all of the eight segmented genes were closely related to the human A(H1N1)pdm09 virus linage isolated in Taiwan. This study may provide a perspective view on natural influenza A virus transmission from the local human population into pet ferrets. PMID:25597188

  16. Cold-induced pseudoneutropenia in human immunodeficiency virus infection: first case report and review of related articles.

    PubMed

    Goyal, Prashant; Agrawal, Dipti; Kailash, J; Singh, Sompal

    2014-09-01

    Cold agglutination of erythrocyte or platelet aggregation in vitro due to cold agglutination are well recognized and extensively studied. Aggregation of leucocyte is a rare hematological phenomenon resulting in a spurious low leucocyte count performed using automated hematology analyzers. Aggregation of leucocyte may relate to malignancy, lymphoproliferative disorders, infection, liver diseases, or autoimmune disorders. It is believed that the mechanism of leucocyte aggregation is mainly related to the use of ethylene diamine tetraacetic acid (EDTA) anticoagulant or is temperature-mediated. Leucoagglutination is associated with either a spurious leucopenia or an underestimation of leucocytosis. This can adversely affect management decisions in terms of unnecessary management of leucopenia or ignoring a leucocytosis that may be indicator of an underlying serious disease. To our knowledge, we report here for the first time the occurrence of pseudoneutropenia due to temperature-mediated, EDTA-independent neutrophil agglutination in adult with human immunodeficiency virus infection. PMID:25332564

  17. Mitochondrial energy-dissipation pathway and cellular redox disruption compromises Arabidopsis resistance to turnip crinkle virus infection.

    PubMed

    Pu, Xiao-Jun; Li, Ya-Nan; Wei, Li-Jie; Xi, De-Hui; Lin, Hong-Hui

    2016-04-29

    Members of the plant mitochondrial energy-dissipation pathway (MEDP) coordinate cellular energy metabolism, redox homeostasis and the balance of ROS production. However, the roles of MEDP members, particularly uncoupling protein (UCP), in resistance to turnip crinkle virus infection (TCV) are poorly understood. Here, we showed that disrupting some MEDP genes compromises plant resistance to TCV viral infection and this is partly associated with damaged photosynthetic characteristics, altered cellular redox and increased ROS production. Experiments using mutant plants with impaired cellular compartment redox poising further demonstrated that impaired chloroplast/mitochondria and cystosol redox increases the susceptibility of plants to viral infection. Our results illustrate a mechanism by which MEDP and cellular compartment redox act in concert to regulate plant resistance to viral infections. PMID:26987718

  18. Cross-Protection of Influenza A Virus Infection by a DNA Aptamer Targeting the PA Endonuclease Domain

    PubMed Central

    Yuan, Shuofeng; Zhang, Naru; Singh, Kailash; Shuai, Huiping; Chu, Hin; Zhou, Jie; Chow, Billy K. C.

    2015-01-01

    Amino acid residues in the N-terminal of the PA subunit (PAN) of the influenza A virus polymerase play critical roles in endonuclease activity, protein stability, and viral RNA (vRNA) promoter binding. In addition, PAN is highly conserved among different subtypes of influenza virus, which suggests PAN to be a desired target in the development of anti-influenza agents. We selected DNA aptamers targeting the intact PA protein or the PAN domain of an H5N1 virus strain using systematic evolution of ligands by exponential enrichment (SELEX). The binding affinities of selected aptamers were measured, followed by an evaluation of in vitro endonuclease inhibitory activity. Next, the antiviral effects of enriched aptamers against influenza A virus infections were examined. A total of three aptamers targeting PA and six aptamers targeting PAN were selected. Our data demonstrated that all three PA-selected aptamers neither inhibited endonuclease activity nor exhibited antiviral efficacy, whereas four of the six PAN-selected aptamers inhibited both endonuclease activity and H5N1 virus infection. Among the four effective aptamers, one exhibited cross-protection against infections of H1N1, H5N1, H7N7, and H7N9 influenza viruses, with a 50% inhibitory concentration (IC50) of around 10 nM. Notably, this aptamer was identified at the 5th round but disappeared after the 10th round of selection, suggesting that the identification and evaluation of aptamers at early rounds of selection may be highly helpful for screening effective aptamers. Overall, our study provides novel insights for screening and developing effective aptamers for use as anti-influenza drugs. PMID:25918143

  19. Prophylactic Administration of Bacterially Derived Immunomodulators Improves the Outcome of Influenza Virus Infection in a Murine Model▿

    PubMed Central

    Norton, Elizabeth B.; Clements, John D.; Voss, Thomas G.; Cárdenas-Freytag, Lucia

    2010-01-01

    Prophylactic or therapeutic immunomodulation is an antigen-independent strategy that induces nonspecific immune system activation, thereby enhancing host defense to disease. In this study, we investigated the effect of prophylactic immunomodulation on the outcome of influenza virus infection using three bacterially derived immune-enhancing agents known for promoting distinct immunological profiles. BALB/c mice were treated nasally with either cholera toxin (CT), a mutant form of the CT-related Escherichia coli heat-labile enterotoxin designated LT(R192G), or CpG oligodeoxynucleotide. Mice were subsequently challenged with a lethal dose of influenza A/PR/8/34 virus 24 h after the last immunomodulation treatment and either monitored for survival or sacrificed postchallenge for viral and immunological analysis. Treatment with the three immunomodulators prevented or delayed mortality and weight loss, but only CT and LT(R192G) significantly reduced initial lung viral loads as measured by plaque assay. Analysis performed 4 days postinfection indicated that prophylactic treatments with CT, LT(R192G), or CpG resulted in significantly increased numbers of CD4 T cells, B cells, and dendritic cells and altered costimulatory marker expression in the airways of infected mice, coinciding with reduced expression of pulmonary chemokines and the appearance of inducible bronchus-associated lymphoid tissue-like structures in the lungs. Collectively, these results suggest that, despite different immunomodulatory mechanisms, CT, LT(R192G), and CpG induce an initial inflammatory process and enhance the immune response to primary influenza virus challenge while preventing potentially damaging chemokine expression. These studies provide insight into the immunological parameters and immune modulation strategies that have the potential to enhance the nonspecific host response to influenza virus infection. PMID:20053748

  20. RIG-I, MDA5 and TLR3 Synergistically Play an Important Role in Restriction of Dengue Virus Infection

    PubMed Central

    Thien, Peiling; Xu, Shengli; Lam, Kong-Peng; Liu, Ding Xiang

    2011-01-01

    Dengue virus (DV) infection is one of the most common mosquito-borne viral diseases in the world. The innate immune system is important for the early detection of virus and for mounting a cascade of defense measures which include the production of type 1 interferon (IFN). Hence, a thorough understanding of the innate immune response during DV infection would be essential for our understanding of the DV pathogenesis. A recent application of the microarray to dengue virus type 1 (DV1) infected lung carcinoma cells revealed the increased expression of both extracellular and cytoplasmic pattern recognition receptors; retinoic acid inducible gene-I (RIG-I), melanoma differentiation associated gene-5 (MDA-5) and Toll-like receptor-3 (TLR3). These intracellular RNA sensors were previously reported to sense DV infection in different cells. In this study, we show that they are collectively involved in initiating an effective IFN production against DV. Cells silenced for these genes were highly susceptible to DV infection. RIG-I and MDA5 knockdown HUH-7 cells and TLR3 knockout macrophages were highly susceptible to DV infection. When cells were silenced for only RIG-I and MDA5 (but not TLR3), substantial production of IFN-β was observed upon virus infection and vice versa. High susceptibility to virus infection led to ER-stress induced apoptosis in HUH-7 cells. Collectively, our studies demonstrate that the intracellular RNA virus sensors (RIG-I, MDA5 and TLR3) are activated upon DV infection and are essential for host defense against the virus. PMID:21245912

  1. Predictors of hospital stay and mortality in dengue virus infection-experience from Aga Khan University Hospital Pakistan

    PubMed Central

    2014-01-01

    Background Dengue virus infection (DVI) is very common infection. There is scarcity of data on factor associated with increased hospital stay and mortality in dengue virus infection (DVI). This study was done to know about factors associated with increased hospital stay and mortality in patients admitted with DVI. Results Out of 532 patients, two third (72.6%) had stay ≤3 days while one third (27.4%) had stay greater than 3 days. The mean length of hospital stay was 3.46 ± 3.45 days. Factors associated with increased hospital stay (>3 days) included AKI (acute kidney injury) (Odd ratio 2.98; 95% CI 1.66-5.34), prolonged prothrombin time (Odd ratio 2.03; 95% CI 1.07-3.84), prolonged activated partial thromboplastin time (aPTT) (Odd ratio 1.80; CI 95% 1.15-2.83) and increased age of > 41.10 years (Odd ratio 1.03; CI 95% 1.01-1.04).Mortality was 1.5%. High mortality was found in those with AKI (P <0.01), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) (P <0.001), respiratory failure (P0.01), prolong PT (P 0.001), prolong aPTT (P0.01) and increased hospital stay (P0.04). Conclusion Increasing age, coagulopathy and acute kidney injury in patients with DVI is associated with increased hospital stay. Morality was more in patients with AKI, DHF and DSS, respiratory failure, coagulopathy and these patients had more prolonged hospitalization. PMID:25064632

  2. Internalization of Sapovirus, a Surrogate for Norovirus, in Romaine Lettuce and the Effect of Lettuce Latex on Virus Infectivity

    PubMed Central

    Esseili, Malak A.; Zhang, Zhenwen

    2012-01-01

    Noroviruses are the leading cause of food-borne outbreaks, including those that involve lettuce. The culturable porcine sapovirus (SaV) was used as a norovirus surrogate to study the persistence and the potential transfer of the virus from roots to leaves and from outer to inner leaves of lettuce plants. Treatment of lettuce with SaV was done through the roots of young plants, the soil, or the outer leaves of mature plants. Sampling of roots, xylem sap, and inner and outer leaves followed by RNA extraction and SaV-specific real-time reverse transcription (RT)-PCR was performed at 2 h and on postinoculation days (PID) 2, 5, 7, 14, and/or 28. When SaV was inoculated through the roots, viral RNA persisted on the roots and in the leaves until PID 28. When the virus was inoculated through the soil, viral RNA was detected on the roots and in the xylem sap until PID 14; viral RNA was detected in the leaves only until PID 2. No infectious virus was detected inside the leaves for either treatment. When SaV was inoculated through the outer leaves, viral RNA persisted on the leaves until PID 14; however, the virus did not transfer to inner leaves. Infectious viral particles on leaves were detected only at 2 h postinoculation. The milky sap (latex) of leaves, but not the roots' xylem sap, significantly decreased virus infectivity when tested in vitro. Collectively, our results showed the transfer of SaV from roots to leaves through the xylem system and the capacity of the sap of lettuce leaves to decrease virus infectivity in leaves. PMID:22752176

  3. Developmental Exposure to Bisphenol A Modulates Innate but Not Adaptive Immune Responses to Influenza A Virus Infection

    PubMed Central

    Roy, Anirban; Bauer, Stephen M.; Lawrence, B. Paige

    2012-01-01

    Bisphenol A (BPA) is used in numerous products, such as plastic bottles and food containers, from which it frequently leaches out and is consumed by humans. There is a growing public concern that BPA exposure may pose a significant threat to human health. Moreover, due to the widespread and constant nature of BPA exposure, not only adults but fetuses and neonates are also exposed to BPA. There is mounting evidence that developmental exposures to chemicals from our environment, including BPA, contribute to diseases late in life; yet, studies of how early life exposures specifically alter the immune system are limited. Herein we report an examination of how maternal exposure to a low, environmentally relevant dose of BPA affects the immune response to infection with influenza A virus. We exposed female mice during pregnancy and through lactation to the oral reference dose for BPA listed by the US Environmental Protection Agency, and comprehensively examined immune parameters directly linked to disease outcomes in adult offspring following infection with influenza A virus. We found that developmental exposure to BPA did not compromise disease-specific adaptive immunity against virus infection, or reduce the host’s ability to clear the virus from the infected lung. However, maternal exposure to BPA transiently reduced the extent of infection-associated pulmonary inflammation and anti-viral gene expression in lung tissue. From these observations, we conclude that maternal exposure to BPA slightly modulates innate immunity in adult offspring, but does not impair the anti-viral adaptive immune response, which is critical for virus clearance and survival following influenza virus infection. PMID:22675563

  4. The Influence of Virus Infection on the Extracellular pH of the Host Cell Detected on Cell Membrane

    PubMed Central

    Liu, Hengjun; Maruyama, Hisataka; Masuda, Taisuke; Honda, Ayae; Arai, Fumihito

    2016-01-01

    Influenza virus infection can result in changes in the cellular ion levels at 2–3 h post-infection. More H+ is produced by glycolysis, and the viral M2 proton channel also plays a role in the capture and release of H+ during both viral entry and egress. Then the cells might regulate the intracellular pH by increasing the export of H+ from the intracellular compartment. Increased H+ export could lead indirectly to increased extracellular acidity. To detect changes in extracellular pH of both virus-infected and uninfected cells, pH sensors were synthesized using polystyrene beads (ϕ1 μm) containing Rhodamine B and Fluorescein isothiocyanate (FITC). The fluorescence intensity of FITC can respond to both pH and temperature. So Rhodamine B was also introduced in the sensor for temperature compensation. Then the pH can be measured after temperature compensation. The sensor was adhered to cell membrane for extracellular pH measurement. The results showed that the multiplication of influenza virus in host cell decreased extracellular pH of the host cell by 0.5–0.6 in 4 h after the virus bound to the cell membrane, compared to that in uninfected cells. Immunostaining revealed the presence of viral PB1 protein in the nucleus of virus-bound cells that exhibited extracellular pH changes, but no PB1 protein are detected in virus-unbound cells where the extracellular pH remained constant. PMID:27582727

  5. The Influence of Virus Infection on the Extracellular pH of the Host Cell Detected on Cell Membrane.

    PubMed

    Liu, Hengjun; Maruyama, Hisataka; Masuda, Taisuke; Honda, Ayae; Arai, Fumihito

    2016-01-01

    Influenza virus infection can result in changes in the cellular ion levels at 2-3 h post-infection. More H(+) is produced by glycolysis, and the viral M2 proton channel also plays a role in the capture and release of H(+) during both viral entry and egress. Then the cells might regulate the intracellular pH by increasing the export of H(+) from the intracellular compartment. Increased H(+) export could lead indirectly to increased extracellular acidity. To detect changes in extracellular pH of both virus-infected and uninfected cells, pH sensors were synthesized using polystyrene beads (ϕ1 μm) containing Rhodamine B and Fluorescein isothiocyanate (FITC). The fluorescence intensity of FITC can respond to both pH and temperature. So Rhodamine B was also introduced in the sensor for temperature compensation. Then the pH can be measured after temperature compensation. The sensor was adhered to cell membrane for extracellular pH measurement. The results showed that the multiplication of influenza virus in host cell decreased extracellular pH of the host cell by 0.5-0.6 in 4 h after the virus bound to the cell membrane, compared to that in uninfected cells. Immunostaining revealed the presence of viral PB1 protein in the nucleus of virus-bound cells that exhibited extracellular pH changes, but no PB1 protein are detected in virus-unbound cells where the extracellular pH remained constant. PMID:27582727

  6. Public health response to commercial airline travel of a person with Ebola virus infection - United States, 2014.

    PubMed

    Regan, Joanna J; Jungerman, Robynne; Montiel, Sonia H; Newsome, Kimberly; Objio, Tina; Washburn, Faith; Roland, Efrosini; Petersen, Emily; Twentyman, Evelyn; Olaiya, Oluwatosin; Naughton, Mary; Alvarado-Ramy, Francisco; Lippold, Susan A; Tabony, Laura; McCarty, Carolyn L; Kinsey, Cara Bicking; Barnes, Meghan; Black, Stephanie; Azzam, Ihsan; Stanek, Danielle; Sweitzer, John; Valiani, Anita; Kohl, Katrin S; Brown, Clive; Pesik, Nicki

    2015-01-30

    Before the current Ebola epidemic in West Africa, there were few documented cases of symptomatic Ebola patients traveling by commercial airline, and no evidence of transmission to passengers or crew members during airline travel. In July 2014 two persons with confirmed Ebola virus infection who were infected early in the Nigeria outbreak traveled by commercial airline while symptomatic, involving a total of four flights (two international flights and two Nigeria domestic flights). It is not clear what symptoms either of these two passengers experienced during flight; however, one collapsed in the airport shortly after landing, and the other was documented to have fever, vomiting, and diarrhea on the day the flight arrived. Neither infected passenger transmitted Ebola to other passengers or crew on these flights. In October 2014, another airline passenger, a U.S. health care worker who had traveled domestically on two commercial flights, was confirmed to have Ebola virus infection. Given that the time of onset of symptoms was uncertain, an Ebola airline contact investigation in the United States was conducted. In total, follow-up was conducted for 268 contacts in nine states, including all 247 passengers from both flights, 12 flight crew members, eight cleaning crew members, and one federal airport worker (81 of these contacts were documented in a report published previously). All contacts were accounted for by state and local jurisdictions and followed until completion of their 21-day incubation periods. No secondary cases of Ebola were identified in this investigation, confirming that transmission of Ebola during commercial air travel did not occur. PMID:25632954

  7. Tenofovir in treatment of Iranian patients with chronic hepatitis B virus infection: An open-label case series

    PubMed Central

    Ataei, Behrooz; Khodadoostan, Mahsa; Pouria, Babk; Adibi, Peyman

    2016-01-01

    Objective: Tenofovir is among the first-line treatments for chronic hepatitis B (CHB) virus infection. We evaluated the efficacy and safety of Tenofovir in treatment of Iranian patients with CHB. Methods: Forty treatment-native patients with CHB but without concurrent hepatitis C or human immunodeficiency virus infections were treated with Tenobiovir(™) 300 mg/day. The hepatitis B virus (HBV) DNA load, hepatitis B e antigen (HBe Ag), anti-hepatitis B e antibody (HBe Ab), liver enzymes, and creatinine were measured before and at least 3 months after the treatment. Findings: The mean age of patients was 38.1 ± 12.4 years and 65% of them were male. Seventeen (42.5%) patients were HBe Ag-positive and 15 (37.5%) patients had alanine aminotransferase (ALT) of two times above the normal. The HBV DNA load was significantly decreased after the treatment (P < 0.001). Twenty-seven (67.5%) patients had viral load of ≤2000 IU/ml and 22 (55%) patients had undetectable HBV DNA level after the treatment. Among positive HBe Ag patients, the HBe Ag became negative in 15 (88.2%) patients after the treatment and HBe Ab became positive in 3 (17.6%) patients. Liver enzymes’ levels were significantly decreased after the treatment (P <0.05) and ALT transaminase level became normalized in 86.7% (13 out of 15) of cases with baseline levels twice the normal. Conclusion: Treatment response rate to Tenofovir in Iranian patients with CHB was high. The virological and serological response rate and safety of Tenofovir in our population was comparable to other populations. Considering availability and costs, Tenobiovir(™) could be recommended as the first-line therapy of chronic HBV infection in Iran. PMID:27512706

  8. Homo- and Heterosubtypic Low Pathogenic Avian Influenza Exposure on H5N1 Highly Pathogenic Avian Influenza Virus Infection in Wood Ducks (Aix sponsa)

    PubMed Central

    Costa, Taiana P.; Brown, Justin D.; Howerth, Elizabeth W.; Stallknecht, David E.; Swayne, David E.

    2011-01-01

    Wild birds in the Orders Anseriformes and Charadriiformes are the natural reservoirs for avian influenza (AI) viruses. Although they are often infected with multiple AI viruses, the significance and extent of acquired immunity in these populations is not understood. Pre-existing immunity to AI virus has been shown to modulate the outcome of a highly pathogenic avian influenza (HPAI) virus infection in multiple domestic avian species, but few studies have addressed this effect in wild birds. In this study, the effect of pre-exposure to homosubtypic (homologous hemagglutinin) and heterosubtypic (heterologous hemagglutinin) low pathogenic avian influenza (LPAI) viruses on the outcome of a H5N1 HPAI virus infection in wood ducks (Aix sponsa) was evaluated. Pre-exposure of wood ducks to different LPAI viruses did not prevent infection with H5N1 HPAI virus, but did increase survival associated with H5N1 HPAI virus infection. The magnitude of this effect on the outcome of the H5N1 HPAI virus infection varied between different LPAI viruses, and was associated both with efficiency of LPAI viral replication in wood ducks and the development of a detectable humoral immune response. These observations suggest that in naturally occurring outbreaks of H5N1 HPAI, birds with pre-existing immunity to homologous hemagglutinin or neuraminidase subtypes of AI virus may either survive H5N1 HPAI virus infection or live longer than naïve birds and, consequently, could pose a greater risk for contributing to viral transmission and dissemination. The mechanisms responsible for this protection and/or the duration of this immunity remain unknown. The results of this study are important for surveillance efforts and help clarify epidemiological data from outbreaks of H5N1 HPAI virus in wild bird populations. PMID:21253608

  9. Immunization with non-replicating E. coli minicells delivering both protein antigen and DNA protects mice from lethal challenge with lymphocytic choriomeningitis virus

    PubMed Central

    Giacalone, Matthew J.; Zapata, Juan C.; Berkley, Neil L.; Sabbadini, Roger A.; Chu, Yen-Lin; Salvato, Maria S.; McGuire, Kathleen L.

    2008-01-01

    In the midst of new investigations into the mechanisms of both delivery and protection of new vaccines and vaccine carriers, it has become clear that immunization with delivery mechanisms that do not involve living, replicating organisms are vastly preferred. In this report, non-replicating bacterial minicells simultaneously co-delivering the nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) and the corresponding DNA vaccine were tested for the ability to generate protective cellular immune responses in mice. It was found that good protection (89%) was achieved after intramuscular administration, moderate protection (31%) was achieved after intranasal administration, and less protection (7%) was achieved following gastric immunization. These results provide a solid foundation on which to pursue the use of bacterial minicells as a non-replicating vaccine delivery platform. PMID:17258845

  10. Protection from Severe Influenza Virus Infections in Mice Carrying the Mx1 Influenza Virus Resistance Gene Strongly Depends on Genetic Background

    PubMed Central

    Shin, Dai-Lun; Hatesuer, Bastian; Bergmann, Silke; Nedelko, Tatiana

    2015-01-01

    ABSTRACT Influenza virus infections represent a serious threat to human health. Both extrinsic and intrinsic factors determine the severity of influenza. The MX dynamin-like GTPase 1 (Mx1) gene has been shown to confer strong resistance to influenza A virus infections in mice. Most laboratory mouse strains, including C57BL/6J, carry nonsense or deletion mutations in Mx1 and thus a nonfunctional allele, whereas wild-derived mouse strains carry a wild-type Mx1 allele. Congenic C57BL/6J (B6-Mx1r/r) mice expressing a wild-type allele from the A2G mouse strain are highly resistant to influenza A virus infections, to both mono- and polybasic subtypes. Furthermore, in genetic mapping studies, Mx1 was identified as the major locus of resistance to influenza virus infections. Here, we investigated whether the Mx1 protective function is influenced by the genetic background. For this, we generated a congenic mouse strain carrying the A2G wild-type Mx1 resistance allele on a DBA/2J background (D2-Mx1r/r). Most remarkably, congenic D2-Mx1r/r mice expressing a functional Mx1 wild-type allele are still highly susceptible to H1N1 virus. However, pretreatment of D2-Mx1r/r mice with alpha interferon protected them from lethal infections. Our results showed, for the first time, that the presence of an Mx1 wild-type allele from A2G as such does not fully protect mice from lethal influenza A virus infections. These observations are also highly relevant for susceptibility to influenza virus infections in humans. IMPORTANCE Influenza A virus represents a major health threat to humans. Seasonal influenza epidemics cause high economic loss, morbidity, and deaths each year. Genetic factors of the host strongly influence susceptibility and resistance to virus infections. The Mx1 (MX dynamin-like GTPase 1) gene has been described as a major resistance gene in mice and humans. Most inbred laboratory mouse strains are deficient in Mx1, but congenic B6-Mx1r/r mice that carry the wild-type Mx1

  11. Patterns of Multi-Virus Infections of Watermelon at the Plant and Field Levels in Florida

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The whitefly-transmitted viruses Squash vein yellowing virus (SqVYV) and Cucurbit leaf crumple virus (CuLCrV) have had serious impact on watermelon production in west-central and southwest Florida in recent years. We collected plants randomly from a commercial watermelon field in southwest Florida s...

  12. Epidemiological Analysis of Multi-Virus Infections of Watermelon in Experimental Fields in Southwest Florida

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Whitefly-transmitted Squash vein yellowing virus (SqVYV) and Cucurbit leaf crumple virus (CuLCrV), and aphid-transmitted Papaya ringspot virus type W (PRSV-W) have had serious impact on watermelon production in southwest and west-central Florida in recent years. Tissue blot nucleic acid hybridizati...

  13. Characterization of cytotoxic T lymphocyte function following foot-and-mouth disease virus infection and vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) is an economically important disease of cloven-hoofed animals that remains a global threat to livestock species. The induction of neutralizing antibodies against FMD virus (FMDV) has been the central goal of vaccination efforts against this disease. Although these effort...

  14. Epidemiological Analysis of Multi-Virus Infections of Watermelon in Experimental Fields in Southwest Florida

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The whitefly-transmitted viruses Squash vein yellowing virus (SqVYV) and Cucurbit leaf crumple virus (CuLCrV) have had serious impact on watermelon production in west-central and southwest Florida in recent years. We monitored the progress of SqVYV and CuLCrV and whitefly density in 2.5 acre experim...

  15. Dynamics of cellular immune responses in the acute phase of dengue virus infection.

    PubMed

    Yoshida, Tomoyuki; Omatsu, Tsutomu; Saito, Akatsuki; Katakai, Yuko; Iwasaki, Yuki; Kurosawa, Terue; Hamano, Masataka; Higashino, Atsunori; Nakamura, Shinichiro; Takasaki, Tomohiko; Yasutomi, Yasuhiro; Kurane, Ichiro; Akari, Hirofumi

    2013-06-01

    In this study, we examined the dynamics of cellular immune responses in the acute phase of dengue virus (DENV) infection in a marmoset model. Here, we found that DENV infection in marmosets greatly induced responses of CD4/CD8 central memory T and NKT cells. Interestingly, the strength of the immune response was greater in animals infected with a dengue fever strain than in those infected with a dengue hemorrhagic fever strain of DENV. In contrast, when animals were re-challenged with the same DENV strain used for primary infection, the neutralizing antibody induced appeared to play a critical role in sterilizing inhibition against viral replication, resulting in strong but delayed responses of CD4/CD8 central memory T and NKT cells. The results in this study may help to better understand the dynamics of cellular and humoral immune responses in the control of DENV infection. PMID:23381396

  16. Vaccine-Induced CD107a+ CD4+ T Cells Are Resistant to Depletion following AIDS Virus Infection

    PubMed Central

    Terahara, Kazutaka; Ishii, Hiroshi; Nomura, Takushi; Takahashi, Naofumi; Takeda, Akiko; Shiino, Teiichiro; Tsunetsugu-Yokota, Yasuko

    2014-01-01

    ABSTRACT CD4+ T-cell responses are crucial for effective antibody and CD8+ T-cell induction following virus infection. However, virus-specific CD4+ T cells can be preferential targets for human immunodeficiency virus (HIV) infection. HIV-specific CD4+ T-cell induction by vaccination may thus result in enhancement of virus replication following infection. In the present study, we show that vaccine-elicited CD4+ T cells expressing CD107a are relatively resistant to depletion in a macaque AIDS model. Comparison of virus-specific CD107a, macrophage inflammatory protein-1β, gamma interferon, tumor necrosis factor alpha, and interleukin-2 responses in CD4+ T cells of vaccinated macaques prechallenge and 1 week postchallenge showed a significant reduction in the CD107a− but not the CD107a+ subset after virus exposure. Those vaccinees that failed to control viremia showed a more marked reduction and exhibited significantly higher viral loads at week 1 than unvaccinated animals. Our results indicate that vaccine-induced CD107a− CD4+ T cells are depleted following virus infection, suggesting a rationale for avoiding virus-specific CD107a− CD4+ T-cell induction in HIV vaccine design. IMPORTANCE Induction of effective antibody and/or CD8+ T-cell responses is a principal vaccine strategy against human immunodeficiency virus (HIV) infection. CD4+ T-cell responses are crucial for effective antibody and CD8+ T-cell induction. However, virus-specific CD4+ T cells can be preferential targets for HIV infection. Here, we show that vaccine-induced virus-specific CD107a− CD4+ T cells are largely depleted following infection in a macaque AIDS model. While CD4+ T-cell responses are important in viral control, our results indicate that virus-specific CD107a− CD4+ T-cell induction by vaccination may not lead to efficient CD4+ T-cell responses following infection but rather be detrimental and accelerate viral replication in the acute phase. This suggests that HIV vaccine design

  17. Hemagglutinin Stalk- and Neuraminidase-Specific Monoclonal Antibodies Protect against Lethal H10N8 Influenza Virus Infection in Mice

    PubMed Central

    Wohlbold, Teddy John; Chromikova, Veronika; Tan, Gene S.; Meade, Philip; Amanat, Fatima; Comella, Phillip; Hirsh, Ariana

    2015-01-01

    ABSTRACT Between November 2013 and February 2014, China reported three human cases of H10N8 influenza virus infection in the Jiangxi province, two of which were fatal. Using hybridoma technology, we isolated a panel of H10- and N8-directed monoclonal antibodies (MAbs) and further characterized the binding reactivity of these antibodies (via enzyme-linked immunosorbent assay) to a range of purified virus and recombinant protein substrates. The H10-directed MAbs displayed functional hemagglutination inhibition (HI) and neutralization activity, and the N8-directed antibodies displayed functional neuraminidase inhibition (NI) activity against H10N8. Surprisingly, the HI-reactive H10 antibodies, as well as a previously generated, group 2 hemagglutinin (HA) stalk-reactive antibody, demonstrated NI activity against H10N8 and an H10N7 strain; this phenomenon was absent when virus was treated with detergent, suggesting the anti-HA antibodies inhibited neuraminidase enzymatic activity through steric hindrance. We tested the prophylactic efficacy of one representative H10-reactive, N8-reactive, and group 2 HA stalk-reactive antibody in vivo using a BALB/c challenge model. All three antibodies were protective at a high dose (5 mg/kg). At a low dose (0.5 mg/kg), only the anti-N8 antibody prevented weight loss. Together, these data suggest that antibody targets other than the globular head domain of the HA may be efficacious in preventing influenza virus-induced morbidity and mortality. IMPORTANCE Avian H10N8 and H10N7 viruses have recently crossed the species barrier, causing morbidity and mortality in humans and other mammals. Although these reports are likely isolated incidents, it is possible that more cases may emerge in future winter seasons, similar to H7N9. Furthermore, regular transmission of avian influenza viruses to humans increases the risk of adaptive mutations and reassortment events, which may result in a novel virus with pandemic potential. Currently, no

  18. [Non-invasive diagnostic methods of fibrosis in chronic hepatitis C virus infection: their role in treatment indication, follow-up and assessment of prognosis].

    PubMed

    Pár, Alajos; Vincze, Áron; Pár, Gabriella

    2015-05-24

    Chronic hepatitis C virus infection associated with necroinflammation predisposes to liver fibrosis and cirrhosis, which lead to severe end-stage complications. Staging of fibrosis is of basic importance for the indication of antiviral treatment, for monitoring the response and predicting the prognosis of patients with hepatitis C virus related liver disease. Since liver biopsy, the "gold standard" diagnosis of fibrosis is invasive and it has some other limitations, non-invasive methods have been developed and widely used in the clinical practice. Serum biomarkers and physical approaches measuring liver stiffness by elastography as well as combination algorithms have been gradually been integrated into guidelines resulting in a reduction of the need for liver biopsy. The authors review these non-invasive fibrosis markers and discuss their role in the indication of treatment, follow-up, and assessment of prognosis of patients with chronic hepatitis C virus infection. PMID:26038993

  19. Possible repurposing of seasonal influenza vaccine for prevention of Zika virus infection

    PubMed Central

    Veljkovic, Veljko; Paessler, Slobodan

    2016-01-01

    The in silico analysis shows that the envelope glycoproteins E of Zika viruses (ZIKV) isolated in Asia, Africa and South and Central America encode highly conserved information determining their interacting profile and immunological properties. Previously it was shown that the same information is encoded in the primary structure of the hemagglutinin subunit 1 (HA1) from pdmH1N1 influenza A virus.  This similarity suggests possible repurposing of the seasonal influenza vaccine containing pdmH1N1 component for prevention of the ZIKV infection. PMID:27158449

  20. Cerebral Candidal Abscess and Bovine Viral Diarrhoea Virus Infection in an Aborted Bovine Fetus.

    PubMed

    Vilander, A C; Niles, G A; Frank, C B

    2016-01-01

    Candida species are opportunistic fungi associated with immunosuppression and are the most commonly isolated fungal pathogens from the human central nervous system. Invasive candidiasis is reported uncommonly in animals and there have only been two reports of candidal infection of the brain. This report presents a case of a cerebral candidal abscess in an aborted late-term calf co-infected with bovine viral diarrhoea virus. Candida etchellsii, a species not previously identified as pathogenic, was identified as the causative agent by polymerase chain reaction. PMID:26895887