WorldWideScience

Sample records for models viral infections

  1. Research on viral dynamic models of hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Lequan Min; Xisong Dong

    2004-01-01

    A mathematical model with cytotoxic cells of hepatitis B virus (HBV) infection is set up based on a basic model of virus dynamics without cytotoxic cells and experimental observation of anti-viral drug therapy for HBV infection patients. A quantitative analysis of dynamic behaviors shows that the model has three kinds of equilibrium points, which represent the patient's complete recovery without immune ability, complete recovery with immune ability, and HBV persistent infection at the end of the treatment with drug lamivudine, respectively. Our model may provide possible quantitative interpretations for the treatments of chronic HBV infections with the drug lamivudine, in particularly explain why the plasma virus of Nowak et al.'s patients turnover the original level after stopping the lamivudine treatment.

  2. Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model

    Science.gov (United States)

    Laurie, Karen L.; Guarnaccia, Teagan A.; Carolan, Louise A.; Yan, Ada W. C.; Aban, Malet; Petrie, Stephen; Cao, Pengxing; Heffernan, Jane M.; McVernon, Jodie; Mosse, Jennifer; Kelso, Anne; McCaw, James M.; Barr, Ian G.

    2015-01-01

    Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1–14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season. PMID:25943206

  3. STUDY OF PERSISTENT VIRAL INFECTION IN AN ANIMAL MODEL OF VIRAL MYOCARDITIS BY PCR

    Institute of Scientific and Technical Information of China (English)

    马睿; 陈曙霞; 刘晶星

    2000-01-01

    ffeStnn6 Objectif Etudier ie r6le de l'infection virale persistante dans ie pethog4de de la myOCardite virale.ANt~ L' ARN viral dens ie my~rde et ie mug et l' alteration potholedque du m~rde ent ate ewilnd per la techniquede PCR adns un mangle de myrmrdite virale chez ies ~ris. Rhaltats L 'ARN viral a ate detects an 3'jour dens ie mug etie myrmrde. An 8'jour, I 'ARN viral an niveau du mug a ate pertiellement dewnu then f lorsque l' alteration pethologiquedu myocarde a atteint un maximum. he 12'jour, L' ARN ...

  4. The stability analysis of a general viral infection model with distributed delays and multi-staged infected progression

    Science.gov (United States)

    Wang, Jinliang; Liu, Shengqiang

    2015-01-01

    We investigate an in-host model with general incidence and removal rate, as well as distributed delays in virus infections and in productions. By employing Lyapunov functionals and LaSalle's invariance principle, we define and prove the basic reproductive number R0 as a threshold quantity for stability of equilibria. It is shown that if R0 > 1 , then the infected equilibrium is globally asymptotically stable, while if R0 ⩽ 1 , then the infection free equilibrium is globally asymptotically stable under some reasonable assumptions. Moreover, n + 1 distributed delays describe (i) the time between viral entry and the transcription of viral RNA, (ii) the n - 1 -stage time needed for activated infected cells between viral RNA transcription and viral release, and (iii) the time necessary for the newly produced viruses to be infectious (maturation), respectively. The model can describe the viral infection dynamics of many viruses such as HIV-1, HCV and HBV.

  5. Global analysis of viral infection in an archaeal model system

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    Walid S. Maaty

    2012-12-01

    Full Text Available The origin and evolutionary relationship of viruses is poorly understood. This makes archaeal virus-host of particular interest because the hosts generally root near the base of phylogenetic trees, while some of the viruses have clear structural similarities to those that infect prokaryotic and eukaryotic cells. Despite the advantageous position for use in evolutionary studies, little is known about archaeal viruses or how they interact with their hosts, compared to viruses of bacteria and eukaryotes. In addition, many archaeal viruses have been isolated from extreme environments and present a unique opportunity for elucidating factors that are important for existence at the extremes.. In this article we focus on virus-host interactions using a proteomics approach to study Sulfolobus Turreted Icosahedral Virus (STIV infection of Sulfolobus solfataricus P2. Using cultures grown from the ATCC cell stock, a single cycle of STIV infection was sampled 6 times over a 72 hr period. More than 700 proteins were identified throughout the course of the experiments. Seventy one host proteins were found to change by nearly two-fold (p<0.05 with 40 becoming more abundant and 31 less abundant. The modulated proteins represent 30 different cell pathways and 14 COG groups. 2D gel analysis showed that changes in post translational modifications were a common feature of the affected proteins. The results from these studies showed that the prokaryotic antiviral adaptive immune system CRISPR associated proteins (CAS proteins were regulated in response to the virus infection. It was found that regulated proteins come from mRNAs with a shorter than average half-life. In addition, activity-based protein profiling (ABPP profiling on 2D gels showed caspase, hydrolase and tyrosine phosphatase enzyme activity labeling at the protein isoform level. Together, this data provides a more detailed global view of archaeal cellular responses to viral infection, demonstrates the

  6. [Emergent viral infections

    NARCIS (Netherlands)

    Galama, J.M.D.

    2001-01-01

    The emergence and re-emergence of viral infections is an ongoing process. Large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. Increased travel is leading to a rise in the importation of exotic infecti

  7. New animal models for hepatitis C viral infection and pathogenesis studies

    Institute of Scientific and Technical Information of China (English)

    Dina Kremsdorf; Nicolas Brezillon

    2007-01-01

    Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC).In man, the pathobiological changes associated with HCV infection have been attributed to both the immune system and direct viral cytopathic effects. Until now, the lack of simple culture systems to infect and propagate the virus has hampered progress in understanding the viral life cycle and pathogenesis of HCV infection,including the molecular mechanisms implicated in HCV-induced HCC. This clearly demonstrates the need to develop small animal models for the study of HCV-associated pathogenesis. This review describes and discusses the development of new HCV animal models to study viral infection and investigate the direct effects of viral protein expression on liver disease.

  8. Global stability of a multiple delayed viral infection model with general incidence rate and an application to HIV infection.

    Science.gov (United States)

    Ji, Yu

    2015-06-01

    In this paper, the dynamical behavior of a viral infection model with general incidence rate and two time delays is studied. By using the Lyapunov functional and LaSalle invariance principle, the global stabilities of the infection-free equilibrium and the endemic equilibrium are obtained. We obtain a threshold of the global stability for the uninfected equilibrium, which means the disease will be under control eventually. These results can be applied to a variety of viral infections of disease that would make it possible to devise optimal treatment strategies. Numerical simulations with application to HIV infection are given to verify the analytical results.

  9. Microvesicles and viral infection.

    Science.gov (United States)

    Meckes, David G; Raab-Traub, Nancy

    2011-12-01

    Cells secrete various membrane-enclosed microvesicles from their cell surface (shedding microvesicles) and from internal, endosome-derived membranes (exosomes). Intriguingly, these vesicles have many characteristics in common with enveloped viruses, including biophysical properties, biogenesis, and uptake by cells. Recent discoveries describing the microvesicle-mediated intercellular transfer of functional cellular proteins, RNAs, and mRNAs have revealed additional similarities between viruses and cellular microvesicles. Apparent differences include the complexity of viral entry, temporally regulated viral expression, and self-replication proceeding to infection of new cells. Interestingly, many virally infected cells secrete microvesicles that differ in content from their virion counterparts but may contain various viral proteins and RNAs. For the most part, these particles have not been analyzed for their content or functions during viral infection. However, early studies of microvesicles (L-particles) secreted from herpes simplex virus-infected cells provided the first evidence of microvesicle-mediated intercellular communication. In the case of Epstein-Barr virus, recent evidence suggests that this tumorigenic herpesvirus also utilizes exosomes as a mechanism of cell-to-cell communication through the transfer of signaling competent proteins and functional microRNAs to uninfected cells. This review focuses on aspects of the biology of microvesicles with an emphasis on their potential contributions to viral infection and pathogenesis.

  10. An accurate two-phase approximate solution to the acute viral infection model

    Energy Technology Data Exchange (ETDEWEB)

    Perelson, Alan S [Los Alamos National Laboratory

    2009-01-01

    During an acute viral infection, virus levels rise, reach a peak and then decline. Data and numerical solutions suggest the growth and decay phases are linear on a log scale. While viral dynamic models are typically nonlinear with analytical solutions difficult to obtain, the exponential nature of the solutions suggests approximations can be found. We derive a two-phase approximate solution to the target cell limited influenza model and illustrate the accuracy using data and previously established parameter values of six patients infected with influenza A. For one patient, the subsequent fall in virus concentration was not consistent with our predictions during the decay phase and an alternate approximation is derived. We find expressions for the rate and length of initial viral growth in terms of the parameters, the extent each parameter is involved in viral peaks, and the single parameter responsible for virus decay. We discuss applications of this analysis in antiviral treatments and investigating host and virus heterogeneities.

  11. Viral infection, inflammation and schizophrenia.

    Science.gov (United States)

    Kneeland, Rachel E; Fatemi, S Hossein

    2013-04-05

    Schizophrenia is a severe neurodevelopmental disorder with genetic and environmental etiologies. Prenatal viral/bacterial infections and inflammation play major roles in the genesis of schizophrenia. In this review, we describe a viral model of schizophrenia tested in mice whereby the offspring of mice prenatally infected with influenza at E7, E9, E16, and E18 show significant gene, protein, and brain structural abnormalities postnatally. Similarly, we describe data on rodents exposed to bacterial infection or injected with a synthetic viral mimic (PolyI:C) also demonstrating brain structural and behavioral abnormalities. Moreover, human serologic data has been indispensible in supporting the viral theory of schizophrenia. Individuals born seropositive for bacterial and viral agents are at a significantly elevated risk of developing schizophrenia. While the specific mechanisms of prenatal viral/bacterial infections and brain disorder are unclear, recent findings suggest that the maternal inflammatory response may be associated with fetal brain injury. Preventive and therapeutic treatment options are also proposed. This review presents data related to epidemiology, human serology, and experimental animal models which support the viral model of schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. ModeLang: a new approach for experts-friendly viral infections modeling.

    Science.gov (United States)

    Wasik, Szymon; Prejzendanc, Tomasz; Blazewicz, Jacek

    2013-01-01

    Computational modeling is an important element of systems biology. One of its important applications is modeling complex, dynamical, and biological systems, including viral infections. This type of modeling usually requires close cooperation between biologists and mathematicians. However, such cooperation often faces communication problems because biologists do not have sufficient knowledge to understand mathematical description of the models, and mathematicians do not have sufficient knowledge to define and verify these models. In many areas of systems biology, this problem has already been solved; however, in some of these areas there are still certain problematic aspects. The goal of the presented research was to facilitate this cooperation by designing seminatural formal language for describing viral infection models that will be easy to understand for biologists and easy to use by mathematicians and computer scientists. The ModeLang language was designed in cooperation with biologists and its computer implementation was prepared. Tests proved that it can be successfully used to describe commonly used viral infection models and then to simulate and verify them. As a result, it can make cooperation between biologists and mathematicians modeling viral infections much easier, speeding up computational verification of formulated hypotheses.

  13. Tupaia belangeri as an experimental animal model for viral infection.

    Science.gov (United States)

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori

    2014-01-01

    Tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. The morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the Tupaiidae. Genomic analysis has revealed that the genus Tupaia is closer to humans than it is to rodents. In addition, tupaias are susceptible to hepatitis B virus and hepatitis C virus. The only other experimental animal that has been demonstrated to be sensitive to both of these viruses is the chimpanzee, but restrictions on animal testing have meant that experiments using chimpanzees have become almost impossible. Consequently, the development of the tupaia for use as an animal infection model could become a powerful tool for hepatitis virus research and in preclinical studies on drug development.

  14. Global dynamics of cell mediated immunity in viral infection models with distributed delays

    CERN Document Server

    Nakata, Yukihiko

    2010-01-01

    In this paper, we investigate global dynamics for a system of delay differential equations which describes a virus-immune interaction in \\textit{vivo}. The model has two distributed time delays describing time needed for infection of cell and virus replication. Our model admits three possible equilibria, an uninfected equilibrium and infected equilibrium with or without immune response depending on the basic reproduction number for viral infection $R_{0}$ and for CTL response $R_{1}$ such that $R_{1}1$. The immune activation has a positive role in the reduction of the infection cells and the increasing of the uninfected cells if $R_{1}>1$.

  15. Viral infections in pigeons.

    Science.gov (United States)

    Marlier, D; Vindevogel, H

    2006-07-01

    This review provides a current update on the major viral diseases of the domestic pigeon (Columba livia domestica), based on scientific reports and clinical experience. Paramyxovirus 1, adenovirus, rotavirus, herpesvirus 1, poxvirus and circovirus infections are described according to common clinical signs and target tissues. Since pigeons are sometimes treated as if they were poultry, the review also summarises the common viral infections of poultry for which pigeons are considered resistant. It is hoped that the review will provide a useful reference for veterinarians and others and offer advice on the diagnosis, treatment and prevention of the major infectious diseases of pigeons.

  16. Modelling and analysis of dynamics of viral infection of cells and of interferon resistance

    Science.gov (United States)

    Getto, Ph.; Kimmel, M.; Marciniak-Czochra, A.

    2008-08-01

    Interferons are active biomolecules, which help fight viral infections by spreading from infected to uninfected cells and activate effector molecules, which confer resistance from the virus on cells. We propose a new model of dynamics of viral infection, including endocytosis, cell death, production of interferon and development of resistance. The novel element is a specific biologically justified mechanism of interferon action, which results in dynamics different from other infection models. The model reflects conditions prevailing in liquid cultures (ideal mixing), and the absence of cells or virus influx from outside. The basic model is a nonlinear system of five ordinary differential equations. For this variant, it is possible to characterise global behaviour, using a conservation law. Analytic results are supplemented by computational studies. The second variant of the model includes age-of-infection structure of infected cells, which is described by a transport-type partial differential equation for infected cells. The conclusions are: (i) If virus mortality is included, the virus becomes eventually extinct and subpopulations of uninfected and resistant cells are established. (ii) If virus mortality is not included, the dynamics may lead to extinction of uninfected cells. (iii) Switching off the interferon defense results in a decrease of the sum total of uninfected and resistant cells. (iv) Infection-age structure of infected cells may result in stabilisation or destabilisation of the system, depending on detailed assumptions. Our work seems to constitute the first comprehensive mathematical analysis of the cell-virus-interferon system based on biologically plausible hypotheses.

  17. Methamphetamine mediates immune dysregulation in a murine model of chronic viral infection.

    Directory of Open Access Journals (Sweden)

    Uma eSriram

    2015-08-01

    Full Text Available Methamphetamine (METH is a highly addictive psychostimulant that not only affects the brain and cognitive functions but also greatly impacts the host immune system, rendering the body susceptible to infections and exacerbating the severity of disease. Although there is gathering evidence about METH abuse and increased incidence of HIV and other viral infections, not much is known about the effects on the immune system in a chronic viral infection setting. We have used the lymphocytic choriomeningitis virus (LCMV chronic mouse model of viral infection in a chronic METH environment and demonstrate that METH significantly increases CD3 marker on splenocytes and programmed death -1 (PD-1 expression on T cells, a cell surface signaling molecule known to inhibit T cell function and cause exhaustion in a lymphoid organ. Many of these METH effects were more pronounced during early stage of infection, which are gradually attenuated during later stages of infection. An essential cytokine for T-lymphocyte homeostasis, Interleukin-2 (IL-2 in serum was prominently reduced in METH-exposed infected mice. In addition, the serum pro-inflammatory (TNF, IL12 p70, IL1β, IL-6 and KC-GRO and Th2 (IL-2, IL-10 and IL-4 cytokine profiles were also altered in the presence of METH. Interestingly CXCR3, an inflammatory chemokine receptor, showed significant increase in the METH treated LCMV infected mice. Similarly, compared to only infected mice, epidermal growth factor receptor (EGFR in METH exposed LCMV infected mice were up regulated. Collectively, our data suggest that METH alters systemic, peripheral immune responses and modulates key markers on T cells involved in pathogenesis of chronic viral infection.

  18. Autistic disorder and viral infections.

    Science.gov (United States)

    Libbey, Jane E; Sweeten, Thayne L; McMahon, William M; Fujinami, Robert S

    2005-02-01

    Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions, which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system (CNS), through infection elsewhere in the body acting as a trigger for disease in the CNS, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known. Animal models in which early viral infection results in behavioral changes later in life include the influenza virus model in pregnant mice and the Borna disease virus model in newborn Lewis rats. Many studies over the years have presented evidence both for and against the association of autism with various viral infections. The best association to date has been made between congenital rubella and autism; however, members of the herpes virus family may also have a role in autism. Recently, controversy has arisen as to the involvement of measles virus and/or the measles, mumps, rubella (MMR) vaccine in the development of autism. Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism. Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism.

  19. A nonstandard finite difference scheme for a basic model of cellular immune response to viral infection

    Science.gov (United States)

    Korpusik, Adam

    2017-02-01

    We present a nonstandard finite difference scheme for a basic model of cellular immune response to viral infection. The main advantage of this approach is that it preserves the essential qualitative features of the original continuous model (non-negativity and boundedness of the solution, equilibria and their stability conditions), while being easy to implement. All of the qualitative features are preserved independently of the chosen step-size. Numerical simulations of our approach and comparison with other conventional simulation methods are presented.

  20. Modelling viral infections using zebrafish: Innate immune response and antiviral research.

    Science.gov (United States)

    Varela, Mónica; Figueras, Antonio; Novoa, Beatriz

    2017-03-01

    Zebrafish possess a highly developed immune system that is remarkably similar to the human one. Therefore, it is expected that the majority of the signalling pathways and molecules involved in the immune response of mammals exist and behave similarly in fish. The innate antiviral response depends on the recognition of viral components by host cells. Pattern recognition receptors initiate antimicrobial defence mechanisms via several well-conserved signalling pathways. In this paper, we review current knowledge of the antiviral innate immune response in zebrafish by considering the main molecules that have been characterized and the infection models used for the in vivo study of the antiviral innate immune response. We next summarize published studies in which larval and adult zebrafish were used to study viral diseases of fish, then provide a similar review of studies of human viral diseases in zebrafish and experience with antiviral drug screening in this model organism. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Liposomal nanocontainers as models for viral infection: monitoring viral genomic RNA transfer through lipid membranes.

    Science.gov (United States)

    Bilek, Gerhard; Matscheko, Nena M; Pickl-Herk, Angela; Weiss, Victor U; Subirats, Xavier; Kenndler, Ernst; Blaas, Dieter

    2011-08-01

    After uptake into target cells, many nonenveloped viruses undergo conformational changes in the low-pH environment of the endocytic compartment. This results in exposure of amphipathic viral peptides and/or hydrophobic protein domains that are inserted into and either disrupt or perforate the vesicular membranes. The viral nucleic acids thereby gain access to the cytosol and initiate replication. We here demonstrate the in vitro transfer of the single-stranded positive-sense RNA genome of human rhinovirus 2 into liposomes decorated with recombinant very-low-density lipoprotein receptor fragments. Membrane-attached virions were exposed to pH 5.4, mimicking the in vivo pH environment of late endosomes. This triggered the release of the RNA whose arrival in the liposomal lumen was detected via in situ cDNA synthesis by encapsulated reverse transcriptase. Subsequently, cDNA was PCR amplified. At a low ratio between virions and lipids, RNA transfer was positively correlated with virus concentration. However, membranes became leaky at higher virus concentrations, which resulted in decreased cDNA synthesis. In accordance with earlier in vivo data, the RNA passes through the lipid membrane without causing gross damage to vesicles at physiologically relevant virus concentrations.

  2. Immunogenetics of viral infections.

    Science.gov (United States)

    Martin, Maureen P; Carrington, Mary

    2005-10-01

    The HLA class I and II genes encode molecules that lie at the heart of the acquired immune response against infectious diseases. Associations between these polymorphic loci and genetically complex infectious diseases have been historically elusive, in contrast to the more obvious HLA associations with autoimmune diseases. High resolution molecular typing of large, clinically well-defined cohorts has begun to uncover evidence for the influence of HLA diversity on diseases of viral etiology, such as those caused by HIV-1, hepatitis B virus, hepatitis C virus and human papilloma virus. Combinations of HLA and KIR also appear to affect outcome to viral infection, supporting a role for HLA class I diversity in the innate immune response in addition to the acquired immune response.

  3. Dengue viral infections

    Directory of Open Access Journals (Sweden)

    Gurugama Padmalal

    2010-01-01

    Full Text Available Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections.

  4. Sphingolipids in viral infection.

    Science.gov (United States)

    Schneider-Schaulies, Jürgen; Schneider-Schaulies, Sibylle

    2015-06-01

    Viruses exploit membranes and their components such as sphingolipids in all steps of their life cycle including attachment and membrane fusion, intracellular transport, replication, protein sorting and budding. Examples for sphingolipid-dependent virus entry are found for: human immunodeficiency virus (HIV), which besides its protein receptors also interacts with glycosphingolipids (GSLs); rhinovirus, which promotes the formation of ceramide-enriched platforms and endocytosis; or measles virus (MV), which induces the surface expression of its own receptor CD150 via activation of sphingomyelinases (SMases). While SMase activation was implicated in Ebola virus (EBOV) attachment, the virus utilizes the cholesterol transporter Niemann-Pick C protein 1 (NPC1) as 'intracellular' entry receptor after uptake into endosomes. Differential activities of SMases also affect the intracellular milieu required for virus replication. Sindbis virus (SINV), for example, replicates better in cells lacking acid SMase (ASMase). Defined lipid compositions of viral assembly and budding sites influence virus release and infectivity, as found for hepatitis C virus (HCV) or HIV. And finally, viruses manipulate cellular signaling and the sphingolipid metabolism to their advantage, as for example influenza A virus (IAV), which activates sphingosine kinase 1 and the transcription factor NF-κB.

  5. Assessing pneumococcal meningitis association with viral respiratory infections and antibiotics: insights from statistical and mathematical models.

    Science.gov (United States)

    Opatowski, Lulla; Varon, Emmanuelle; Dupont, Claire; Temime, Laura; van der Werf, Sylvie; Gutmann, Laurent; Boëlle, Pierre-Yves; Watier, Laurence; Guillemot, Didier

    2013-08-01

    Pneumococcus is an important human pathogen, highly antibiotic resistant and a major cause of bacterial meningitis worldwide. Better prevention requires understanding the drivers of pneumococcal infection incidence and antibiotic susceptibility. Although respiratory viruses (including influenza) have been suggested to influence pneumococcal infections, the underlying mechanisms are still unknown, and viruses are rarely considered when studying pneumococcus epidemiology. Here, we propose a novel mathematical model to examine hypothetical relationships between Streptococcus pneumoniae meningitis incidence (SPMI), acute viral respiratory infections (AVRIs) and antibiotic exposure. French time series of SPMI, AVRI and penicillin consumption over 2001-2004 are analysed and used to assess four distinct virus-bacteria interaction submodels, ascribing the interaction on pneumococcus transmissibility and/or pathogenicity. The statistical analysis reveals strong associations between time series: SPMI increases shortly after AVRI incidence and decreases overall as the antibiotic-prescription rate rises. Model simulations require a combined impact of AVRI on both pneumococcal transmissibility (up to 1.3-fold increase at the population level) and pathogenicity (up to threefold increase) to reproduce the data accurately, along with diminished epidemic fitness of resistant pneumococcal strains causing meningitis (0.97 (0.96-0.97)). Overall, our findings suggest that AVRI and antibiotics strongly influence SPMI trends. Consequently, vaccination protecting against respiratory virus could have unexpected benefits to limit invasive pneumococcal infections.

  6. Viral infections of rabbits.

    Science.gov (United States)

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Viral infections in asthma and COPD.

    Science.gov (United States)

    Matsumoto, Koichiro; Inoue, Hiromasa

    2014-03-01

    Airway viral infections are associated with the pathogenesis of asthma and COPD. It has been argued that respiratory syncytial virus (RSV) infection in infancy is a probable causal factor in the development of pediatric asthma. RSV infections tend to induce Th2-biased immune responses in the host airways. RSV infection, atopy, and low pulmonary function in neonates may work synergistically toward the development of pediatric asthma. Human rhinovirus (HRV) is a representative virus associated with the exacerbation of asthma in both children and adults. Viral infections trigger innate immune responses including granulocytic inflammation and worsen the underlying inflammation due to asthma and COPD. The innate immune responses involve type-I and -III interferon (IFN) production, which plays an important role in anti-viral responses, and the airway epithelia of asthmatics reportedly exhibit defects in the virus-induced IFN responses, which renders these individuals more susceptible to viral infection. A similarly impaired IFN response is seen in COPD, and several investigators propose that latent adenoviral infection may be involved in COPD development. Persistent RSV infections were detected in a sub-population of patients with COPD and were associated with the accelerated decline of lung function. The virus-induced upregulation of co-inhibitory molecules in the airway epithelium partly accounts for the persistent infections. Experimental animal models for virus-asthma/COPD interactions have shed light on the underlying immune mechanisms and are expected to help develop novel approaches to treat respiratory diseases.

  8. Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

    Science.gov (United States)

    Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

  9. Mast cells in viral infections

    Directory of Open Access Journals (Sweden)

    Piotr Witczak

    2012-04-01

    Full Text Available  There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9, but also RIG-I-like and NOD-like molecules. Furthermore, mast cells generate various mediators, cytokines and chemokines which modulate the intensity of inflammation and regulate the course of innate and adaptive anti-viral immunity. Indirect evidence for the role of mast cells in viral infections is also provided by clinical observations and results of animal studies. Currently, more and more data indicate that mast cells can be infected by some viruses (dengue virus, adenoviruses, hantaviruses, cytomegaloviruses, reoviruses, HIV-1 virus. It is also demonstrated that mast cells can release pre formed mediators as well as synthesize de novo eicosanoids in response to stimulation by viruses. Several data indicate that virus-stimulated mast cells secrete cytokines and chemokines, including interferons as well as chemokines with a key role in NK and Tc lymphocyte influx. Moreover, some information indicates that mast cell stimulation via TLR3, TLR7/8 and TLR9 can affect their adhesion to extracellular matrix proteins and chemotaxis, and influence expression of some membrane molecules. Critical analysis of current data leads to the conclusion that it is not yet possible to make definitive statements about the role of mast cells in innate and acquired defense mechanisms developing in the course of viral infection and/or pathomechanisms of viral diseases.

  10. Integrin Activation and Viral Infection

    Institute of Scientific and Technical Information of China (English)

    Shan-dian GAO; Jun-zheng DU; Jian-hua ZHOU; Hui-yun CHANG; Qing-ge XIE

    2008-01-01

    Integrins are members of a ubiquitous membrane receptor family which includes 18 different α subunits and 8 β subunits forming more than 20 α/β heterodimers. Integrins play key functions in vascular endothelial cell and tumour cell adhesion, lymphocyte trafficking, tumor growth and viral infection. Current understanding of the molecular basis of integrins as viral receptors has been achieved through many decades of study into the biology of transmembrane glycoproteins and their interactions with several viruses. This review provides a summary of the current knowledge on the molecular bases of interactions between viruses and integrins, which are of potential practical significance. Inhibition of virus-integrin interactions at the points of virus attachment or entry will provide a novel approach for the therapeutic treatment of viral diseases.

  11. Pediatric Asthma and Viral Infection.

    Science.gov (United States)

    Garcia-Garcia, M Luz; Calvo Rey, Cristina; Del Rosal Rabes, Teresa

    2016-05-01

    Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. Bronchiolitis is the most common acute respiratory infection in children under 1year of age, and the most common cause of hospitalization in this age group. RSV accounts for approximately 70% of all these cases, followed by rhinovirus, adenovirus, metapneumovirus and bocavirus. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In any case, sufficient evidence is available to corroborate the existence of this association, which is particularly strong when the causative agent of bronchiolitis is rhinovirus. The pathogenic role of respiratory viruses as triggers for exacerbations in asthmatic patients has not been fully characterized. However, it is clear that respiratory viruses, and in particular rhinovirus, are the most common causes of exacerbation in children, and some type of respiratory virus has been identified in over 90% of children hospitalized for an episode of wheezing. Changes in the immune response to viral infections in genetically predisposed individuals are very likely to be the main factors involved in the association between viral infection and asthma.

  12. Recycling Endosomes and Viral Infection

    Directory of Open Access Journals (Sweden)

    Sílvia Vale-Costa

    2016-03-01

    Full Text Available Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral–host interactions occurring on the endocytic recycling compartment (ERC, and mediated by its regulatory Ras-related in brain (Rab GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition.

  13. Drug Use and Viral Infections (HIV, Hepatitis)

    Science.gov (United States)

    ... Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) HIV/AIDS Mental Health Military Opioid Overdose Reversal ... Publications » DrugFacts » Drug Use and Viral Infections (HIV, Hepatitis) Drug Use and Viral Infections (HIV, Hepatitis) Email Facebook Twitter Revised March ...

  14. Optimal cytoplasmic transport in viral infections.

    Directory of Open Access Journals (Sweden)

    Maria R D'Orsogna

    Full Text Available For many viruses, the ability to infect eukaryotic cells depends on their transport through the cytoplasm and across the nuclear membrane of the host cell. During this journey, viral contents are biochemically processed into complexes capable of both nuclear penetration and genomic integration. We develop a stochastic model of viral entry that incorporates all relevant aspects of transport, including convection along microtubules, biochemical conversion, degradation, and nuclear entry. Analysis of the nuclear infection probabilities in terms of the transport velocity, degradation, and biochemical conversion rates shows how certain values of key parameters can maximize the nuclear entry probability of the viral material. The existence of such "optimal" infection scenarios depends on the details of the biochemical conversion process and implies potentially counterintuitive effects in viral infection, suggesting new avenues for antiviral treatment. Such optimal parameter values provide a plausible transport-based explanation of the action of restriction factors and of experimentally observed optimal capsid stability. Finally, we propose a new interpretation of how genetic mutations unrelated to the mechanism of drug action may nonetheless confer novel types of overall drug resistance.

  15. Viral marketing as epidemiological model

    CERN Document Server

    Rodrigues, Helena Sofia

    2015-01-01

    In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of the critical factors to this communications strategy effectiveness remain largely unknown, the mathematical models in epidemiology are presented in this marketing specific field. In this paper, an epidemiological model SIR (Susceptible- Infected-Recovered) to study the effects of a viral marketing strategy is presented. It is made a comparison between the disease parameters and the marketing application, and simulations using the Matlab software are performed. Finally, some conclusions are given and their marketing impli...

  16. Mast cells in viral infections

    OpenAIRE

    Piotr Witczak; Ewa Brzezińska-Błaszczyk

    2012-01-01

     There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9), but also RIG-I-like and NOD-like molecules. Fu...

  17. Modeling chronic hepatitis B or C virus infection during antiviral therapy using an analogy to enzyme kinetics: long-term viral dynamics without rebound and oscillation.

    Science.gov (United States)

    Takayanagi, Toshiaki

    2013-12-01

    The basic model for chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection during therapy enables us to analyze short-term viral kinetics. However, the model is not useful for analyzing long-term viral kinetics. Here, I suggest a new model that was obtained by introducing Michaelis-Menten kinetics into the basic model. The new model can exhibit long-term viral kinetics without rebound and oscillation, unlike the basic model. The value of the parameter K in the new model is analogous to the Michaelis constant Km and is predicted to be approximately less than 10(10)/ml.

  18. Rate-equation modelling and ensemble approach to extraction of parameters for viral infection-induced cell apoptosis and necrosis

    Science.gov (United States)

    Domanskyi, Sergii; Schilling, Joshua E.; Gorshkov, Vyacheslav; Libert, Sergiy; Privman, Vladimir

    2016-09-01

    We develop a theoretical approach that uses physiochemical kinetics modelling to describe cell population dynamics upon progression of viral infection in cell culture, which results in cell apoptosis (programmed cell death) and necrosis (direct cell death). Several model parameters necessary for computer simulation were determined by reviewing and analyzing available published experimental data. By comparing experimental data to computer modelling results, we identify the parameters that are the most sensitive to the measured system properties and allow for the best data fitting. Our model allows extraction of parameters from experimental data and also has predictive power. Using the model we describe interesting time-dependent quantities that were not directly measured in the experiment and identify correlations among the fitted parameter values. Numerical simulation of viral infection progression is done by a rate-equation approach resulting in a system of "stiff" equations, which are solved by using a novel variant of the stochastic ensemble modelling approach. The latter was originally developed for coupled chemical reactions.

  19. STUDY OF PERSISTENT VIRAL INFECTION IN AN ANIMALMODEL OF VIRAL MYOCARDITIS BY PCR

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study the role of persistent viral infection in the mechanism of viral myocarditis. Methods A mice model of CVB3m viral myocarditis was made and the viral RNA in mice myocardium and whole blood sample was tested by using polymerase chain reaction ( PCR ) technique. The pathological changes in mice myocardium were determined. Results On day 3, the viral gene in whole blood and myocardium was found, which partly became negative on day 8, but the change of myocardial pathology became obvious. Although the blood specimens were tested negatively on day 12, the viral gene in mice myocardium remained positive within 120d. Conclusion This study indicates that persistent viral infection plays a role in the pathogenesis of viral myocarditis.

  20. Immune therapy of a persistent and disseminated viral infection.

    OpenAIRE

    Ahmed, R.; Jamieson, B D; Porter, D D

    1987-01-01

    The mechanism of viral clearance was studied by using the mouse model of chronic infection with lymphocytic choriomeningitis virus. Distinct patterns of viral clearance and histopathology were observed in different organs after adoptive immune therapy of persistently infected (carrier) mice. Clearance from the liver occurred within 30 days and was accompanied by extensive mononuclear cell infiltrates and necrosis of hepatocytes. Infectious virus and viral antigen were eliminated concurrently....

  1. Effects of cannabinoids and their receptors on viral infections.

    Science.gov (United States)

    Tahamtan, Alireza; Tavakoli-Yaraki, Masoumeh; Rygiel, Tomasz P; Mokhtari-Azad, Talat; Salimi, Vahid

    2016-01-01

    Cannabinoids, the active ingredient in marijuana, and their derivatives have received remarkable attention in the last two decades because they can affect tumor growth and metastasis. There is a large body of evidence from in vivo and in vitro models showing that cannabinoids and their receptors influence the immune system, viral pathogenesis, and viral replication. The present study reviews current insights into the role of cannabinoids and their receptors on viral infections. The results reported here indicate that cannabinoids and their receptors have different sequels for viral infection. Although activation or inhibition of cannabinoid receptors in the majority of viral infections are proper targets for development of safe and effective treatments, caution is required before using pharmaceutical cannabinoids as a treatment agent for patients with viral infections.

  2. Studying the immune response to human viral infections using zebrafish.

    Science.gov (United States)

    Goody, Michelle F; Sullivan, Con; Kim, Carol H

    2014-09-01

    Humans and viruses have a long co-evolutionary history. Viral illnesses have and will continue to shape human history: from smallpox, to influenza, to HIV, and beyond. Animal models of human viral illnesses are needed in order to generate safe and effective antiviral medicines, adjuvant therapies, and vaccines. These animal models must support the replication of human viruses, recapitulate aspects of human viral illnesses, and respond with conserved immune signaling cascades. The zebrafish is perhaps the simplest, most commonly used laboratory model organism in which innate and/or adaptive immunity can be studied. Herein, we will discuss the current zebrafish models of human viral illnesses and the insights they have provided. We will highlight advantages of early life stage zebrafish and the importance of innate immunity in human viral illnesses. We will also discuss viral characteristics to consider before infecting zebrafish with human viruses as well as predict other human viruses that may be able to infect zebrafish.

  3. Innate immune response to viral infection.

    Science.gov (United States)

    Koyama, Shohei; Ishii, Ken J; Coban, Cevayir; Akira, Shizuo

    2008-09-01

    In viral infections the host innate immune system is meant to act as a first line defense to prevent viral invasion or replication before more specific protection by the adaptive immune system is generated. In the innate immune response, pattern recognition receptors (PRRs) are engaged to detect specific viral components such as viral RNA or DNA or viral intermediate products and to induce type I interferons (IFNs) and other pro-inflammatory cytokines in the infected cells and other immune cells. Recently these innate immune receptors and their unique downstream pathways have been identified. Here, we summarize their roles in the innate immune response to virus infection, discrimination between self and viral nucleic acids and inhibition by virulent factors and provide some recent advances in the coordination between innate and adaptive immune activation.

  4. Clinical disease severity of respiratory viral co-infection versus single viral infection: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Sandra A Asner

    Full Text Available Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections.We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS. A random-effects model was used to conduct the meta-analyses.Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS (mean difference (MD -0.20 days, 95% CI -0.94, 0.53, p = 0.59, or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09 were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001 with viral co-infection as compared to other age groups (I2 for subgroup analysis 64%, p = 0.04.No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation.

  5. Oxygen tension level and human viral infections.

    Science.gov (United States)

    Morinet, Frédéric; Casetti, Luana; François, Jean-Hugues; Capron, Claude; Pillet, Sylvie

    2013-09-01

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. viral infections of the central nervous system

    African Journals Online (AJOL)

    Viral infections of the central nervous system (CNS) include both acute and chronic conditions ... ADEM is a rare, immune-mediated disorder that is triggered by an environmental stimulus in ... difficulties and apathy. Typically there is cognitive ...

  7. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  8. Respiratory Viral Infections in Chronic Lung Diseases.

    Science.gov (United States)

    Britto, Clemente J; Brady, Virginia; Lee, Seiwon; Dela Cruz, Charles S

    2017-03-01

    Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis (CF) and interstitial lung diseases (ILD), affect many individuals worldwide. Patients with these chronic lung diseases are susceptible to respiratory lung infections and some of these viral infections can contribute to disease pathogenesis. This review highlights the associations of lung infections and the respective chronic lung diseases and how infection in the different lung diseases affects disease exacerbation and progression. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Fish viral infections in northwest of Spain.

    Science.gov (United States)

    Ledo, A; Lupiani, B; Dopazo, C P; Toranzo, A E; Barja, J L

    1990-06-01

    During a three years survey, a total of 149 samples from 20 farms of rainbow trout, salmon and turbot were examined for the presence of virus with the purpose to study the viral infections affecting cultured fish and their incidence in the fishfarms of Northwestern Spain. Infectious pancreatic necrosis virus (IPNV) was the only viral agent isolated from salmonid fish. Fry and fingerlings of trout showed the highest infection rate (24%). This virus was not detected in broodstock or embryonated eggs, although it was isolated from ovaric and seminal fluids and from juvenile carriers. From 24 samples of salmon analyzed, IPNV was only detected in one sample of juveniles. Examination of turbot led the isolation of a new virus belonging to the reoviridae family, which affected to the ongrowing population. All of the IPNV tested belonged to serotype Sp regardless of the origin of the trout stocks. During the monitorization of imported embryonated eggs, no virus was detected from any of the samples. However, in some case, IPNV was isolated when testing the fry obtained in our laboratory from those samples of imported eggs. Our findings indicate that: i) the analysis of fingerlings increase the probability to detect viral infections allowing us an optimal control of importations, and ii) most of the viral infections of fish take place in the own fish farms. The detection of mixed viral and bacterial infections emphasize the importance of carrying out an integral microbiological analysis to determine the causal agent(s) of fish mortalities.

  10. Impacts of Humanized Mouse Models on the Investigation of HIV-1 Infection: Illuminating the Roles of Viral Accessory Proteins in Vivo

    Directory of Open Access Journals (Sweden)

    Eri Yamada

    2015-03-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 encodes four accessory genes: vif, vpu, vpr, and nef. Recent investigations using in vitro cell culture systems have shed light on the roles of these HIV-1 accessory proteins, Vif, Vpr, Vpu, and Nef, in counteracting, modulating, and evading various cellular factors that are responsible for anti-HIV-1 intrinsic immunity. However, since humans are the exclusive target for HIV-1 infection, conventional animal models are incapable of mimicking the dynamics of HIV-1 infection in vivo. Moreover, the effects of HIV-1 accessory proteins on viral infection in vivo remain unclear. To elucidate the roles of HIV-1 accessory proteins in the dynamics of viral infection in vivo, humanized mouse models, in which the mice are xenotransplanted with human hematopoietic stem cells, has been utilized. This review describes the current knowledge of the roles of HIV-1 accessory proteins in viral infection, replication, and pathogenicity in vivo, which are revealed by the studies using humanized mouse models.

  11. Mathematical modeling of the specific T cell response to a viral infection

    OpenAIRE

    Bidot, Caroline

    2006-01-01

    T cell is one of the most important cells in specific immunity. In order to devise a tool for understanding and predicting some mechanisms of the immune system, a model for T cell response is proposed. The T lymphocyte activation by the recognition of a peptide carried by an antigen presenting cell is an essential step of this immune response. T cell activation was modelled by a system of ordinary differential equations of chemical kinetics type, representing the temporal evolution of the con...

  12. Modeling Shrimp Biomass and Viral Infection for Production of Biological Countermeasures

    Science.gov (United States)

    2005-12-09

    proved in [3] using weak formulations, and in [4] semigroup theory is used to prove existence and uniqueness of solutions. For systems with time dependent...H.T. Banks and F. Kappel, Transformation semigroups and L1-approximation for size- structured population models, Semigroup Forum, 38 (1989), 141–155

  13. Mesenchymal Stromal Cells and Viral Infection

    Directory of Open Access Journals (Sweden)

    Maytawan Thanunchai

    2015-01-01

    Full Text Available Mesenchymal Stromal Cells (MSCs are a subset of nonhematopoietic adult stem cells, readily isolated from various tissues and easily culture-expanded ex vivo. Intensive studies of the immune modulation and tissue regeneration over the past few years have demonstrated the great potential of MSCs for the prevention and treatment of steroid-resistant acute graft-versus-host disease (GvHD, immune-related disorders, and viral diseases. In immunocompromised individuals, the immunomodulatory activities of MSCs have raised safety concerns regarding the greater risk of primary viral infection and viral reactivation, which is a major cause of mortality after allogeneic transplantation. Moreover, high susceptibilities of MSCs to viral infections in vitro could reflect the destructive outcomes that might impair the clinical efficacy of MSCs infusion. However, the interplay between MSCs and virus is like a double-edge sword, and it also provides beneficial effects such as allowing the proliferation and function of antiviral specific effector cells instead of suppressing them, serving as an ideal tool for study of viral pathogenesis, and protecting hosts against viral challenge by using the antimicrobial activity. Here, we therefore review favorable and unfavorable consequences of MSCs and virus interaction with the highlight of safety and efficacy for applying MSCs as cell therapy.

  14. Viral markers in HIV infection and AIDS.

    Science.gov (United States)

    Cunningham, A L; Dwyer, D E; Dowton, D N

    1993-01-01

    Viral and immune markers are used for monitoring either progression of human immunodeficiency virus (HIV) disease or response to antiviral therapy. Ideal properties of viral markers are that they are present in all HIV-infected persons at all stages of disease, that they are related to disease pathogenesis, that they can be easily quantitated, that this quantitation correlates rapidly and predictably with both disease stage and response to antivirals, and that they can be developed into rapid, reproducible automated tests. Currently available viral markers include HIV p24 antigenemia (after acid glycine dissociation), anti-p24 antibody titres, quantitative DNA and RNA polymerase chain reaction performed on cells and plasma, and HIV isolate phenotype. In Australia, these markers have been studied in acute HIV seroconversion, in neonatal infection, in body fluids other than blood, and in monitoring of response to antiviral drug therapy.

  15. Keratinocytes derived from chicken embryonic stem cells support Marek's disease virus infection: a highly differentiated cell model to study viral replication and morphogenesis.

    Science.gov (United States)

    Couteaudier, Mathilde; Courvoisier, Katia; Trapp-Fragnet, Laetitia; Denesvre, Caroline; Vautherot, Jean-François

    2016-01-07

    Marek's disease is a virus disease with worldwide distribution that causes major losses to poultry production. Vaccines against Marek's disease virus, an oncogenic alphaherpesvirus, reduce tumour formation but have no effect on virus shedding. Successful horizontal virus transmission is linked to the active viral replication in feather follicle epithelial cells of infected chickens, from which infectious viral particles are shed into the environment. The feather follicle epithelium is the sole tissue in which those infectious particles are produced and no in vitro cell-systems can support this highly efficient morphogenesis. We previously characterized embryonic stem-cell-derived keratinocytes, showing they display a marker-gene profile similar to skin keratinocytes, and therefore we tested their susceptibility to Marek's disease virus infection. We show herein that keratinocytes derived from chicken embryonic stem-cells are fully permissive to the replication of either non-pathogenic or pathogenic Marek's disease viruses. All viruses replicated on all three keratinocyte lines and kinetics of viral production as well as viral loads were similar to those obtained on primary cells. Morphogenesis studies were conducted on infected keratinocytes and on corneocytes, showing that all types of capsids/virions were present inside the cells, but extracellular viruses were absent. The keratinocyte lines are the first epithelial cell-line showing ectodermal specific markers supporting Marek's disease virus replication. In this in vitro model the replication lead to the production of cell-associated viral progeny. Further work will be devoted to the study of relationship between 3D differentiation of keratinocytes and Marek's disease virus replication.

  16. A viral infection of the hands: Orf

    Directory of Open Access Journals (Sweden)

    Mehmet Uluğ

    2013-03-01

    Full Text Available Orf is a viral infection transmitted to humans from sheep and goats. In this report, three cases with orf were presented.Two of our patients had lesions on only one hand, whereas one patient had additional lesions on the other hand. Thelesions were most commonly located on the dorsal aspect of the fingers and typically started as a painless itchy maculethat became papular and, subsequently, purulent with a necrotic center. The lesions were managed conservatively, andno specific therapy was undertaken. The lesions regressed spontaneously and slowly without scarring during the nextfive weeks. In conclusion, we are of the opinion that human infection with orf will continue to occur, and can occur anywhere;thus, all physicians should be aware of the possibility of orf infection and consider orf in the differential diagnosisof cases with relevant animal exposure. J Microbiol Infect Dis 2013; 3(1: 41-44Key words: Orf, skin infection, zoonoses

  17. Virion-targeted viral inactivation: new therapy against viral infection.

    Science.gov (United States)

    Okui, N; Kitamura, Y; Kobayashi, N; Sakuma, R; Ishikawa, T; Kitamura, T

    2001-01-01

    Acquired immune deficiency syndrome (AIDS) is resistant to all current therapy. Gene therapy is an attractive alternative or additive to current, unsatisfactory AIDS therapy. To develop an antiviral molecule targeting viral integrase (HIV IN), we generated a single-chain antibody, termed scAb, which interacted with human immunodeficiency virus type 1 (HIV-1) IN and inhibited virus replication at the integration step when expressed intracellularly. To reduce infectivity from within the virus particles, we made expression plasmids (pC-scAbE-Vpr, pC-scAbE-CA, and pC-scAbE-WXXF), which expressed the anti-HIV IN scAb fused to the N-terminus of HIV-1-associated accessory protein R (Vpr), capsid protein (CA), and specific binding motif to Vpr (WXXF), respectively. All fusion proteins were tagged with a nine-amino acid peptide derived from influenza virus hemagglutinin (HA) at the C terminus. The fusion molecules, termed scAbE-Vpr, scAbE-CA, and scAbE-WXXF, interacted specifically with HIV IN immobilized on a nitrocellulose membrane. Immunoblot analysis showed that scAbE-Vpr, scAbE-CA, and scAbE-WXXF were incorporated into the virions produced by cotransfection of 293T cells with HIV-1 infectious clone DNA (pLAI) and pC-scAbE-Vpr, pC-scAbE-WXXF. A multinuclear activation galactosidase indicator (MAGI) assay revealed that the virions released from 293T cells cotransfected with pLAI and pC-scAbE-Vpr, pC-scAbE-WXXF had as little 1000-fold of the infectivity of the control wild-type virions, which were produced from the 293T cells transfected with pLAI alone. Furthermore, the virions produced from the 293T cells cotransfected with pLAI and an scAb expression vector (pC-scAb) showed only 1% of the infectivity of the control HIV-1 in a MAGI assay, although scAb was not incorporated into the virions. In either instance, the total quantity of the progeny virions released from the transfected 293T cells and the patterns of the virion proteins were hardly affected by the presence of

  18. ASTHMA AND VIRAL INFECTIONS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    D. Sh. Macharadze

    2014-01-01

    Full Text Available Viruses are the most common pathogens of acute respiratory diseases — most often causing mild symptoms of common cold: cough, runny nose, temperature increases. At the same time, 1/3 of children have the following symptoms of lower respiratory tract disorders: shortness of breath, wheezing, coughing, respiratory failure. Virus-induced wheezing are risk factors for development of asthma in childhood. Recent clinical and scientific data suggest: the more difficult are viral respiratory infections in young children, the higher their risk of asthma later on. Another feature is that children with allergic diseases are much more likely to have viral respiratory infections(and with longer clinical course, compared with children without atopy. The use of ibuprofen is safe for children over 3 months, including suffering from bronchial asthma.

  19. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

    Directory of Open Access Journals (Sweden)

    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  20. Recurrent and Sustained Viral Infections in Primary Immunodeficiencies

    Science.gov (United States)

    Ruffner, Melanie A.; Sullivan, Kathleen E.; Henrickson, Sarah E.

    2017-01-01

    Viral infections are commonplace and often innocuous. Nevertheless, within the population of patients with primary immunodeficiencies (PIDDs), viral infections can be the feature that drives a diagnostic evaluation or can be the most significant morbidity for the patient. This review is focused on the viral complications of PIDDs. It will focus on respiratory viruses, the most common type of viral infection in the general population. Children and adults with an increased frequency or severity of respiratory viral infections are often referred for an immunologic evaluation. The classic teaching is to investigate humoral function in people with recurrent sinopulmonary infections, but this is often interpreted to mean recurrent bacterial infections. Recurrent or very severe viral infections may also be a harbinger of a primary immunodeficiency as well. This review will also cover persistent cutaneous viral infections, systemic infections, central nervous system infections, and gastrointestinal infections. In each case, the specific viral infections may drive a diagnostic evaluation that is specific for that type of virus. This review also discusses the management of these infections, which can become problematic in patients with PIDDs. PMID:28674531

  1. 一类具有免疫反应时滞病毒感染模型%A Delayed Viral Infection Model with Two Immune Responses

    Institute of Scientific and Technical Information of China (English)

    宋强; 蔡钶金

    2013-01-01

    In this paper,we study the global dynamics of a delayed viral infection model with two immune responses (CTL immune response and antibody immune response).We derive the basic reproduction number R0,the CTL immune response reproduction number Rc,the antibody immune response reproduction number Ra for the viral infection,and establish that the global dynamics are completely determined by the values of R0,Ra and Rc.Moreover,the global properties of the model are obtainedby using Lyapunov functional.%讨论了一类具有CTL免疫反应和抗体免疫时滞病毒感染模型的全局动力学性质,分别得到了基本再生数Ro,CTL免疫再生数Rc,抗体免疫再生数Ra.通过应用Lyapunov泛函方法,证明了系统的全局动力学性质完全由Ro,Ra和Rc来确定.

  2. Suppression of viral infectivity through lethal defection

    Science.gov (United States)

    Grande-Pérez, Ana; Lázaro, Ester; Lowenstein, Pedro; Domingo, Esteban; Manrubia, Susanna C.

    2005-01-01

    RNA viruses replicate with a very high error rate and give rise to heterogeneous, highly plastic populations able to adapt very rapidly to changing environments. Viral diseases are thus difficult to control because of the appearance of drug-resistant mutants, and it becomes essential to seek mechanisms able to force the extinction of the quasispecies before adaptation emerges. An alternative to the use of conventional drugs consists in increasing the replication error rate through the use of mutagens. Here, we report about persistent infections of lymphocytic choriomeningitis virus treated with fluorouracil, where a progressive debilitation of infectivity leading to eventual extinction occurs. The transition to extinction is accompanied by the production of large amounts of RNA, indicating that the replicative ability of the quasispecies is not strongly impaired by the mutagen. By means of experimental and theoretical approaches, we propose that a fraction of the RNA molecules synthesized can behave as a defective subpopulation able to drive the viable class extinct. Our results lead to the identification of two extinction pathways, one at high amounts of mutagen, where the quasispecies completely loses its ability to infect and replicate, and a second one, at lower amounts of mutagen, where replication continues while the infective class gets extinct because of the action of defectors. The results bear on a potential application of increased mutagenesis as an antiviral strategy in that low doses of a mutagenic agent may suffice to drive persistent virus to extinction. PMID:15767582

  3. Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    Maurizia Rossana Brunetto; Piero Colombatto; Ferruccio Bonino

    2009-01-01

    The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/ hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an "automatic pilot" for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients.

  4. Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

    Science.gov (United States)

    Brunetto, Maurizia Rossana; Colombatto, Piero; Bonino, Ferruccio

    2009-01-01

    The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an “automatic pilot” for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients. PMID:19195054

  5. OCULAR MANIFESTATIONS OF VIRAL INFECTIONS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    E. Yu. Markovа

    2016-01-01

    Full Text Available In case of viral infections, ophthalmologists, pediatricians and general practitioners should all be aware of ocular manifestations of these diseases. According to our observations, despite the presence of corneal disorders, in 95 percent of children changes were reversible and in 1.5 months visual acuity was high. Only in five percent of cases despite the intensive therapy, patients had bacterial complications, causing a decrease in visual acuity.The combined  efforts of infectious disease specialists and ophthalmologists as well as timely and proper treatment are required to reduce the inflammation symptoms and prevent complications. By adding Ophtalmoferon® medication to the complex therapy of ocular surface diseases we observed its high therapeutic efficacy and a good safety profile. This medication is available in the form of ready-to-use eye drops, unlike other antiviral agents, improving  its compliance in outpatients.

  6. Viral DNA in horses infected with equine infectious anemia virus.

    OpenAIRE

    Rice, N R; Lequarré, Anne-Sophie; Casey, J W; Lahn, S; Stephens, R. M.; Edwards, J.

    1989-01-01

    The amount and distribution of viral DNA were established in a horse acutely infected with the Wyoming strain of equine infectious anemia virus (EIAV). The highest concentration of viral DNA were found in the liver, lymph nodes, bone marrow, and spleen. The kidney, choroid plexus, and peripheral blood leukocytes also contained viral DNA, but at a lower level. It is estimated that at day 16 postinoculation, almost all of the viral DNA was located in the tissues, with the liver alone containing...

  7. Phosphorylation of the viral coat protein regulates RNA virus infection

    Directory of Open Access Journals (Sweden)

    Hoover HS

    2016-11-01

    Full Text Available Haley S Hoover, C Cheng Kao Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA Abstract: Coat proteins (CPs are the most abundant protein produced during a viral infection. CPs have been shown to regulate the infection processes of RNA viruses, including RNA replication and gene expression. The numerous activities of the CP in infection are likely to require regulation, possibly through posttranslational modifications. Protein posttranslational modifications are involved in signal transduction, expanding and regulating protein function, and responding to changes in the environment. Accumulating evidence suggests that phosphorylation of viral CPs is involved in the regulation of the viral infection process from enabling virion disassembly to regulation of viral protein synthesis and replication. CP phosphorylation also affects viral trafficking and virion assembly. This review focuses on the regulatory roles that phosphorylation of CPs has in the life cycle of viruses with RNA genomes. Keywords: viral capsid protein, posttranslational modification, phosphorylation, protein–RNA interaction

  8. THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION

    Science.gov (United States)

    Kilbourne, Edwin D.

    1957-01-01

    The administration of cortisone to chicken embryos infected with influenza B virus results in (a) an initial inhibition of viral synthesis and (b) an eventual increase in the final yield of virus attained. Increased yields of virus are attained regardless of the number of viral particles in the infecting inoculum or the proportion of particles which are infective. Changes in the distribution ratios of allantoic fluid and intramembrane virus are effected by cortisone only as the secondary result of reduction in viral synthesis. The manifest effect of cortisone on influenza A virus increase is inhibitory unless inocula containing relatively high proportions of inactive viral particles are used. PMID:13481248

  9. [Viral nosocomial infections: the problem of contemporary hospital management].

    Science.gov (United States)

    Hermanowska-Szpakowicz, Teresa; Zajkowska, Joanna M; Pancewicz, Sławomir A; Kondrusik, Maciej; Grygorczuk, Sambor S

    2003-01-01

    The most frequent viral pathogens which are the cause of nosocomial infections were presented. Influenza and parainfluenza viruses as well as RS virus affect frequently respiratory tract. So called enteric viruses which are rotaviruses, adenoviruses, small round viruses, astroviruses, caliciviruses, corona viruses, Coxackie, ECHO may be the agents of disorders in digestive tract in the form of intoxications. Viruses of viral hepatitis B, C, D and HIV, CMV, EBV may be the source of nosocomial viral infections transmitted by blood (transfusions).

  10. Aspirin-triggered resolvin D1 reduces pneumococcal lung infection and inflammation in a viral and bacterial coinfection pneumonia model.

    Science.gov (United States)

    Wang, Hao; Anthony, Desiree; Yatmaz, Selcuk; Wijburg, Odilia; Satzke, Catherine; Levy, Bruce; Vlahos, Ross; Bozinovski, Steven

    2017-09-15

    Formyl peptide receptor 2/lipoxin A4 (LXA4) receptor (Fpr2/ALX) co-ordinates the transition from inflammation to resolution during acute infection by binding to distinct ligands including serum amyloid A (SAA) and Resolvin D1 (RvD1). Here, we evaluated the proresolving actions of aspirin-triggered RvD1 (AT-RvD1) in an acute coinfection pneumonia model. Coinfection with Streptococcus pneumoniae and influenza A virus (IAV) markedly increased pneumococcal lung load and neutrophilic inflammation during the resolution phase. Fpr2/ALX transcript levels were increased in the lungs of coinfected mice, and immunohistochemistry identified prominent Fpr2/ALX immunoreactivity in bronchial epithelial cells and macrophages. Levels of circulating and lung SAA were also highly increased in coinfected mice. Therapeutic treatment with exogenous AT-RvD1 during the acute phase of infection (day 4-6 post-pneumococcal inoculation) significantly reduced the pneumococcal load. AT-RvD1 also significantly reduced neutrophil elastase (NE) activity and restored total antimicrobial activity in bronchoalveolar lavage (BAL) fluid (BALF) of coinfected mice. Pneumonia severity, as measured by quantitating parenchymal inflammation or alveolitis was significantly reduced with AT-RvD1 treatment, which also reduced the number of infiltrating lung neutrophils and monocytes/macrophages as assessed by flow cytometry. The reduction in distal lung inflammation in AT-RvD1-treated mice was not associated with a significant reduction in inflammatory and chemokine mediators. In summary, we demonstrate that in the coinfection setting, SAA levels were persistently increased and exogenous AT-RvD1 facilitated more rapid clearance of pneumococci in the lungs, while concurrently reducing the severity of pneumonia by limiting excessive leukocyte chemotaxis from the infected bronchioles to distal areas of the lungs. © 2017 The Author(s).

  11. Functional Role of Infective Viral Particles on Metal Reduction

    Energy Technology Data Exchange (ETDEWEB)

    Coates, John D.

    2014-04-01

    A proposed strategy for the remediation of uranium (U) contaminated sites was based on the immobilization of U by reducing the oxidized soluble U, U(VI), to form a reduced insoluble end product, U(IV). Previous studies identified Geobacter sp., including G. sulfurreducens and G. metallireducens, as predominant U(VI)-reducing bacteria under acetate-oxidizing and U(VI)-reducing conditions. Examination of the finished genome sequence annotation of the canonical metal reducing species Geobacter sulfurreducens strain PCA and G. metallireduceans strain GS-15 as well as the draft genome sequence of G. uraniumreducens strain Rf4 identified phage related proteins. In addition, the completed genome for Anaeromyxobacter dehalogenans and the draft genome sequence of Desulfovibrio desulfuricans strain G20, two more model metal-reducing bacteria, also revealed phage related sequences. The presence of these gene sequences indicated that Geobacter spp., Anaeromyxobacter spp., and Desulfovibrio spp. are susceptible to viral infection. Furthermore, viral populations in soils and sedimentary environments in the order of 6.4×10{sup 6}–2.7×10{sup 10} VLP’s cm{sup -3} have been observed. In some cases, viral populations exceed bacterial populations in these environments suggesting that a relationship may exist between viruses and bacteria. Our preliminary screens of samples collected from the ESR FRC indicated that viral like particles were observed in significant numbers. The objective of this study was to investigate the potential functional role viruses play in metal reduction specifically Fe(III) and U(VI) reduction, the environmental parameters affecting viral infection of metal reducing bacteria, and the subsequent effects on U transport.

  12. Estimating Acute Viral Hepatitis Infections From Nationally Reported Cases

    Science.gov (United States)

    Liu, Stephen; Roberts, Henry; Jiles, Ruth B.; Holmberg, Scott D.

    2014-01-01

    Objectives. Because only a fraction of patients with acute viral hepatitis A, B, and C are reported through national surveillance to the Centers for Disease Control and Prevention, we estimated the true numbers. Methods. We applied a simple probabilistic model to estimate the fraction of patients with acute hepatitis A, hepatitis B, and hepatitis C who would have been symptomatic, would have sought health care tests, and would have been reported to health officials in 2011. Results. For hepatitis A, the frequencies of symptoms (85%), care seeking (88%), and reporting (69%) yielded an estimate of 2730 infections (2.0 infections per reported case). For hepatitis B, the frequencies of symptoms (39%), care seeking (88%), and reporting (45%) indicated 18 730 infections (6.5 infections per reported case). For hepatitis C, the frequency of symptoms among injection drug users (13%) and those infected otherwise (48%), proportion seeking care (88%), and percentage reported (53%) indicated 17 100 infections (12.3 infections per reported case). Conclusions. These adjustment factors will allow state and local health authorities to estimate acute hepatitis infections locally and plan prevention activities accordingly. PMID:24432918

  13. DNA cleavage enzymes for treatment of persistent viral infections: Recent advances and the pathway forward

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Nicholas D., E-mail: nweber@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Aubert, Martine, E-mail: maubert@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Dang, Chung H., E-mail: cdang@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Stone, Daniel, E-mail: dstone2@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Jerome, Keith R., E-mail: kjerome@fhcrc.org [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Department of Microbiology, University of Washington, Seattle, WA 98195 (United States)

    2014-04-15

    Treatment for most persistent viral infections consists of palliative drug options rather than curative approaches. This is often because long-lasting viral DNA in infected cells is not affected by current antivirals, providing a source for viral persistence and reactivation. Targeting latent viral DNA itself could therefore provide a basis for novel curative strategies. DNA cleavage enzymes can be used to induce targeted mutagenesis of specific genes, including those of exogenous viruses. Although initial in vitro and even in vivo studies have been carried out using DNA cleavage enzymes targeting various viruses, many questions still remain concerning the feasibility of these strategies as they transition into preclinical research. Here, we review the most recent findings on DNA cleavage enzymes for human viral infections, consider the most relevant animal models for several human viral infections, and address issues regarding safety and enzyme delivery. Results from well-designed in vivo studies will ideally provide answers to the most urgent remaining questions, and allow continued progress toward clinical application. - Highlights: • Recent in vitro and in vivo results for DNA cleavage enzymes targeting persistent viral infections. • Analysis of the best animal models for testing enzymes for HBV, HSV, HIV and HPV. • Challenges facing in vivo delivery of therapeutic enzymes for persistent viral infections. • Safety issues to be addressed with proper animal studies.

  14. Feasibility of dsRNA treatment for post-clearing SPF shrimp stocks of newly discovered viral infections using Laem Singh virus (LSNV) as a model.

    Science.gov (United States)

    Saksmerprome, Vanvimon; Charoonnart, Patai; Flegel, Timothy W

    2017-05-02

    Using post-larvae derived from specific pathogen free (SPF) stocks in penaeid shrimp farming has led to a dramatic increase in production. At the same time, new pathogens of farmed shrimp are continually being discovered. Sometimes these pathogens are carried by shrimp and other crustaceans as persistent infections without gross signs of disease. Thus it is that a 5-generation stock of Penaeus monodon SPF for several pathogens was found, post-stock-development, to be persistently-infected with newly-discovered Laem Singh virus (LSNV). In this situation, the stock developers were faced with destroying their existing stock (developed over a long period at considerable cost) and starting the whole stock development process anew in order to add LSNV to its SPF list. As an alternative, it was hypothesized that injection of complementary dsRNA into viral-infected broodstock prior to mating might inhibit replication of the target virus sufficiently to reduce or eliminate its transmission to their offspring. Subsequent selection of uninfected offspring would allow for post-clearing of LSNV from the existing stock and for conversion of the stock to LSNV-free status. Testing this hypothesis using the LSNV-infected stock described above, we found that transmission was substantially reduced in several treated broodstock compared to much higher transmission in buffer-injected broodstock. Based on these results, the model is proposed for post-clearing of SPF stocks using dsRNA treatment. The model may also be applicable to post-clearing of exceptional, individual performers from grow-out ponds for return to a nucleus breeding center. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Stochastic extinction of viral infectivity through the action of defectors

    Science.gov (United States)

    Iranzo, J.; Manrubia, S. C.

    2009-01-01

    The high error rates of RNA viruses at replication suggest they might be close to the extinction threshold predicted by quasispecies theory. Hence, moderate increases in the mutation rate could drive them to extinction. In persistent infections of an RNA virus treated with a mutagen, it has been observed that infectivity eventually disappears, although the replicative ability of the virus is not affected. By means of a simple model that takes into account two phenotypic traits, we demonstrate that extinction is a purely stochastic phenomenon caused by the intermittent outbreaks of a defective, non-infective subpopulation. The transition between dynamics dominated by population fluctuations (finite system size N) and the mean-field behavior (N→∞) is characterized. We discuss the implications of this alternative pathway to viral extinction.

  16. HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model.

    Science.gov (United States)

    Honeycutt, Jenna B; Wahl, Angela; Archin, Nancie; Choudhary, Shailesh; Margolis, David; Garcia, J Victor

    2013-10-24

    The major targets of HIV infection in humans are CD4⁺ T cells. CD4⁺ T cell depletion is a hallmark of AIDS. Previously, the SCID-hu thy/liv model was used to study the effect of HIV on thymopoeisis in vivo. However, these mice did not develop high levels of peripheral T cell reconstitution and required invasive surgery for infection and analysis. Here, we describe a novel variant of this model in which thy/liv implantation results in systemic reconstitution with human T cells in the absence of any other human hematopoietic lineages. NOD/SCID-hu thy/liv and NSG-hu thy/liv mice were created by implanting human fetal thymus and liver tissues under the kidney capsule of either NOD/SCID or NSG mice. In contrast to NOD/SCID-hu thy/liv mice that show little or no human cells in peripheral blood or tissues, substantial systemic human reconstitution occurs in NSG-hu thy/liv. These mice are exclusively reconstituted with human T cells (i.e. T-cell only mice or TOM). Despite substantial levels of human T cells no signs of graft-versus-host disease (GVHD) were noted in these mice over a period of 14 months. TOM are readily infected after parenteral exposure to HIV-1. HIV replication is sustained in peripheral blood at high levels and results in modest reduction of CD4⁺ T cells. HIV-1 replication in TOM responds to daily administration of combination antiretroviral therapy (ART) resulting in strong suppression of virus replication as determined by undetectable viral load in plasma. Latently HIV infected resting CD4⁺ T cells can be isolated from suppressed mice that can be induced to express HIV ex-vivo upon activation demonstrating the establishment of latency in vivo. NSG-hu thy/liv mice are systemically reconstituted with human T cells. No other human lymphoid lineages are present in these mice (i.e. monocytes/macrophages, B cells and DC are all absent). These T cell only mice do not develop GVHD, are susceptible to HIV-1 infection and can efficiently maintain virus

  17. The Viral Polymerase Inhibitor 7-Deaza-2'-C-Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model.

    Directory of Open Access Journals (Sweden)

    Joanna Zmurko

    2016-05-01

    Full Text Available Zika virus (ZIKV is an emerging flavivirus typically causing a dengue-like febrile illness, but neurological complications, such as microcephaly in newborns, have potentially been linked to this viral infection. We established a panel of in vitro assays to allow the identification of ZIKV inhibitors and demonstrate that the viral polymerase inhibitor 7-deaza-2'-C-methyladenosine (7DMA efficiently inhibits replication. Infection of AG129 (IFN-α/β and IFN-γ receptor knock-out mice with ZIKV resulted in acute neutrophilic encephalitis with viral antigens accumulating in neurons of the brain and spinal cord. Additionally, high levels of viral RNA were detected in the spleen, liver and kidney, and levels of IFN-γ and IL-18 were systematically increased in serum of ZIKV-infected mice. Interestingly, the virus was also detected in testicles of infected mice. In line with its in vitro anti-ZIKV activity, 7DMA reduced viremia and delayed virus-induced morbidity and mortality in infected mice, which also validates this small animal model to assess the in vivo efficacy of novel ZIKV inhibitors. Since AG129 mice can generate an antibody response, and have been used in dengue vaccine studies, the model can also be used to assess the efficacy of ZIKV vaccines.  .

  18. Respiratory viral infection predisposing for bacterial disease : a concise review

    NARCIS (Netherlands)

    Hament, JM; Kimpen, JLL; Fleer, A; Wolfs, TFW

    1999-01-01

    Although bacterial superinfection in viral respiratory disease is a clinically well documented phenomenon, the pathogenic mechanisms are still poorly understood. Recent studies have revealed some of the mechanisms involved. Physical damage to respiratory cells as a result of viral infection may lead

  19. Prostaglandin E2 As a Modulator of Viral Infections

    Science.gov (United States)

    Sander, Willem J.; O'Neill, Hester G.; Pohl, Carolina H.

    2017-01-01

    Viral infections are a major cause of infectious diseases worldwide. Inflammation and the immune system are the major host defenses against these viral infection. Prostaglandin E2 (PGE2), an eicosanoid generated by cyclooxygenases, has been shown to modulate inflammation and the immune system by regulating the expression/concentration of cytokines. The effect of PGE2 on viral infection and replication is cell type- and virus-family-dependent. The host immune system can be modulated by PGE2, with regards to immunosuppression, inhibition of nitrogen oxide (NO) production, inhibition of interferon (IFN) and apoptotic pathways, and inhibition of viral receptor expression. Furthermore, PGE2 can play a role in viral infection directly by increasing the production and release of virions, inhibiting viral binding and replication, and/or stimulating viral gene expression. PGE2 may also have a regulatory role in the induction of autoimmunity and in signaling via Toll-like receptors. In this review the known effects of PGE2 on the pathogenesis of various infections caused by herpes simplex virus, rotavirus, influenza A virus and human immunodeficiency virus as well the therapeutic potential of PGE2 are discussed. PMID:28261111

  20. Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.

    Directory of Open Access Journals (Sweden)

    Katja Pfafferott

    Full Text Available Cellular immune responses during acute Hepatitis C virus (HCV and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%. The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.

  1. Modeling the impact of hepatitis C viral clearance on end-stage liver disease in an HIV co-infected cohort with targeted maximum likelihood estimation.

    Science.gov (United States)

    Schnitzer, Mireille E; Moodie, Erica E M; van der Laan, Mark J; Platt, Robert W; Klein, Marina B

    2014-03-01

    Despite modern effective HIV treatment, hepatitis C virus (HCV) co-infection is associated with a high risk of progression to end-stage liver disease (ESLD) which has emerged as the primary cause of death in this population. Clinical interest lies in determining the impact of clearance of HCV on risk for ESLD. In this case study, we examine whether HCV clearance affects risk of ESLD using data from the multicenter Canadian Co-infection Cohort Study. Complications in this survival analysis arise from the time-dependent nature of the data, the presence of baseline confounders, loss to follow-up, and confounders that change over time, all of which can obscure the causal effect of interest. Additional challenges included non-censoring variable missingness and event sparsity. In order to efficiently estimate the ESLD-free survival probabilities under a specific history of HCV clearance, we demonstrate the double-robust and semiparametric efficient method of Targeted Maximum Likelihood Estimation (TMLE). Marginal structural models (MSM) can be used to model the effect of viral clearance (expressed as a hazard ratio) on ESLD-free survival and we demonstrate a way to estimate the parameters of a logistic model for the hazard function with TMLE. We show the theoretical derivation of the efficient influence curves for the parameters of two different MSMs and how they can be used to produce variance approximations for parameter estimates. Finally, the data analysis evaluating the impact of HCV on ESLD was undertaken using multiple imputations to account for the non-monotone missing data.

  2. Immunological aspects in viral hepatitis B and C infection.

    Science.gov (United States)

    Manea, Irena; Manea, Cristian Nicolae; Miron, Nicolae; Cristea, Victor

    2011-01-01

    Worldwide, viral hepatitis chronic infections are a serious health problem and a very interesting topic for both clinicians and researchers. Viral hepatitis has a variety of clinical forms: mild, inactive or severe and with a slow evolution, whose architectural structure of the hepatic tissue evolves towards cirrhosis or hepatocellular carcinoma. Sometimes, the virally induced hepatic injury evolves spectacularly and rapidly leads to exitus. The factors that generate this evolution pattern depend on the immune response of the host and equally on the viral survival and immune surveillance avoidance strategies. This paper aims to resume new discoveries in the field of immunology of the B and C viral hepatitis infection, from the perspective of the complex interactions between virus and host.

  3. Lower respiratory tract viral infections: Diagnostic role of exfoliative cytology.

    Science.gov (United States)

    Martínez-Girón, Rafael; Pantanowitz, Liron

    2017-07-01

    Viral lower respiratory tract infections (VLRTI) remain one of the most common causes of morbidity and mortality worldwide. For many years, the diagnosis of VLRTI was based on laboratory techniques such as viral isolation in cell culture, antigen detection by direct fluorescent antibody staining, and rapid enzyme immunoassay. Radiological imaging and morphology also play an important role in diagnosing these infections. Exfoliative cytology provides a simple, rapid, inexpensive, and valuable means to diagnose and manage VLRTI. Here we review viral-associated cytomorphological changes seen in exfoliated cells of the lower respiratory tract. Diagn. Cytopathol. 2017;45:614-620. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Viral infection, atopy and mycosis fungoides

    DEFF Research Database (Denmark)

    Morales, Maria; Olsen, Jørn; Johansen, P.

    2003-01-01

    involving seven rare cancers, including MF, was conducted from 1995 to 1998. Patients between 35 and 69 years of age diagnosed with MF (n=140) were recruited, and the diagnoses were verified by a reference pathologist, who classified 83 cases as definitive and 35 cases as possible; 22 cases were...... colon cancer patients and 3566 subjects selected from population registers. Information on infections, skin pathology and clinical history 5 years before the diagnosis of MF was used to estimate odds ratios (ORs) derived from logistic regression-modelling, which included gender, age and country...

  5. The Ins and Outs of Viral Infection: Keystone Meeting Review

    Directory of Open Access Journals (Sweden)

    Sara W. Bird

    2014-09-01

    Full Text Available Newly observed mechanisms for viral entry, assembly, and exit are challenging our current understanding of the replication cycle of different viruses. To address and better understand these mechanisms, a Keystone Symposium was organized in the snowy mountains of Colorado (“The Ins and Outs of Viral Infection: Entry, Assembly, Exit, and Spread”; 30 March–4 April 2014, Beaver Run Resort, Breckenridge, Colorado, organized by Karla Kirkegaard, Mavis Agbandje-McKenna, and Eric O. Freed. The meeting served to bring together cell biologists, structural biologists, geneticists, and scientists expert in viral pathogenesis to discuss emerging mechanisms of viral ins and outs. The conference was organized around different phases of the viral replication cycle, including cell entry, viral assembly and post-assembly maturation, virus structure, cell exit, and virus spread. This review aims to highlight important topics and themes that emerged during the conference.

  6. Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells.

    Science.gov (United States)

    Mayer, Bryan T; Krantz, Elizabeth M; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T; Gantt, Soren

    2017-06-15

    Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine.IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We

  7. Interactions between airway epithelial cells and dendritic cells during viral infections using an in vitro co-culture model

    Science.gov (United States)

    Rationale: Historically, single cell culture models have been limited in pathological and physiological relevance. A co-culture model of dendritic cells (DCs) and differentiated human airway epithelial cells was developed to examine potential interactions between these two cell t...

  8. Viral infections in mice with reconstituted human immune system components.

    Science.gov (United States)

    Münz, Christian

    2014-09-01

    Pathogenic viruses are often difficult to study due to their exclusive tropism for humans. The development of mice with human immune system components opens the possibility to study those human pathogens with a tropism for the human hematopoietic lineage in vivo. These include HCMV, EBV, KSHV, HIV, HTLV-1, dengue virus and JC virus. Furthermore, some human pathogens, like HSV-2, adenovirus, HCV, HBV and influenza A virus, with an additional tropism for somatic mouse tissues or for additional transplanted human tissues, mainly liver, have been explored in these models. The cellular tropism of these viruses, their associated diseases and primarily cell-mediated immune responses to these viral infections will be discussed in this review. Already some exciting information has been gained from these novel chimeric in vivo models and future avenues to gain more insights into the pathology, but also potential therapies, will be outlined. Although the respective in vivo models of human immune responses can still be significantly improved, they already provide preclinical systems for in vivo studies of important viral pathogens of humans.

  9. Viral exploitation of actin:force-generation and scaffolding functions in viral infection

    Institute of Scientific and Technical Information of China (English)

    Mark Spear; Yuntao Wu

    2014-01-01

    As a fundamental component of the host cellular cytoskeleton, actin is routinely engaged by infecting viruses. Furthermore, viruses from diverse groups, and infecting diverse hosts, have convergently evolved an array of mechanisms for manipulating the actin cytoskeleton for efifcacious infection. An ongoing chorus of research now indicates that the actin cytoskeleton is critical for viral replication at many stages of the viral life cycle, including binding, entry, nuclear localization, genomic transcription and reverse transcription, assembly, and egress/dissemination. Speciifcally, viruses subvert the force-generating and macromolecular scaffolding properties of the actin cytoskeleton to propel viral surifng, internalization, and migration within the cell. Additionally, viruses utilize the actin cytoskeleton to support and organize assembly sites, and eject budding virions for cell-to-cell transmission. It is the purpose of this review to provide an overview of current research, focusing on the various mechanisms and themes of virus-mediated actin modulation described therein.

  10. Invariant NKT cells: regulation and function during viral infection.

    Directory of Open Access Journals (Sweden)

    Jennifer A Juno

    Full Text Available Natural killer T cells (NKT cells represent a subset of T lymphocytes that express natural killer (NK cell surface markers. A subset of NKT cells, termed invariant NKT cells (iNKT, express a highly restricted T cell receptor (TCR and respond to CD1d-restricted lipid ligands. iNKT cells are now appreciated to play an important role in linking innate and adaptive immune responses and have been implicated in infectious disease, allergy, asthma, autoimmunity, and tumor surveillance. Advances in iNKT identification and purification have allowed for the detailed study of iNKT activity in both humans and mice during a variety of chronic and acute infections. Comparison of iNKT function between non-pathogenic simian immunodeficiency virus (SIV infection models and chronic HIV-infected patients implies a role for iNKT activity in controlling immune activation. In vitro studies of influenza infection have revealed novel effector functions of iNKT cells including IL-22 production and modulation of myeloid-derived suppressor cells, but ex vivo characterization of human iNKT cells during influenza infection are lacking. Similarly, as recent evidence suggests iNKT involvement in dengue virus pathogenesis, iNKT cells may modulate responses to a number of emerging pathogens. This Review will summarize current knowledge of iNKT involvement in responses to viral infections in both human and mouse models and will identify critical gaps in knowledge and opportunities for future study. We will also highlight recent efforts to harness iNKT ligands as vaccine adjuvants capable of improving vaccination-induced cellular immune responses.

  11. RNAi, a new therapeutic strategy against viral infection

    Institute of Scientific and Technical Information of China (English)

    Fischer L. TAN; James Q. YIN

    2004-01-01

    RNA interference (RNAi) is an adaptive defense mechanism triggered by double-stranded RNA (dsRNA). It is a powerful reverse genetic tool that has been widely employed to silence gene expression in mammalian and human cells.RNAi-based gene therapies, especially in viral diseases have become more and more interesting and promising. Recently,small interfering RNA (siRNA) can be used to protect host from viral infection, inhibit the expression of viral antigen and accessory genes, control the transcription and replication of viral genome, hinder the assembly of viral particles, and display influences in virus-host interactions. In this review, we attempt to present recent progresses of this breakthrough technology in the above fields and summarize the possibilities of siRNA-based drugs.

  12. Benign Testis Mass After Viral Infection

    Directory of Open Access Journals (Sweden)

    Robbie Hurtt

    2017-05-01

    Full Text Available We present two cases of viral associated orchitis and subsequent testis masses concerning for malignancy both on physical exam and scrotal ultrasound. In both cases, the patients underwent radical orchiectomy after a discussion of management options. Both pathologic analyses were negative for malignancy, and our literature search revealed no other similar case reports. We review our two cases specifically, as well as briefly review orchitis and discuss possible management strategies of similar cases.

  13. Benign Testis Mass After Viral Infection.

    Science.gov (United States)

    Hurtt, Robbie; Pound, Charles; Bean, Christopher

    2017-05-01

    We present two cases of viral associated orchitis and subsequent testis masses concerning for malignancy both on physical exam and scrotal ultrasound. In both cases, the patients underwent radical orchiectomy after a discussion of management options. Both pathologic analyses were negative for malignancy, and our literature search revealed no other similar case reports. We review our two cases specifically, as well as briefly review orchitis and discuss possible management strategies of similar cases.

  14. Examination of a Viral Infection Mimetic Model in Human iPS Cell-Derived Insulin-Producing Cells and the Anti-Apoptotic Effect of GLP-1 Analogue.

    Directory of Open Access Journals (Sweden)

    Megu Yamaguchi Baden

    Full Text Available Viral infection is associated with pancreatic beta cell destruction in fulminant type 1 diabetes mellitus. The aim of this study was to investigate the acceleration and protective mechanisms of beta cell destruction by establishing a model of viral infection in pancreatic beta cells.Polyinosinic:polycytidylic acid was transfected into MIN6 cells and insulin-producing cells differentiated from human induced pluripotent stem cells via small molecule applications. Gene expression was analyzed by real-time PCR, and apoptosis was evaluated by caspase-3 activity and TUNEL staining. The anti-apoptotic effect of Exendin-4 was also evaluated.Polyinosinic:polycytidylic acid transfection led to elevated expression of the genes encoding IFNα, IFNβ, CXCL10, Fas, viral receptors, and IFN-inducible antiviral effectors in MIN6 cells. Exendin-4 treatment suppressed the elevated gene expression levels and reduced polyinosinic:polycytidylic acid-induced apoptosis both in MIN6 cells and in insulin-producing cells from human induced pluripotent stem cells. Glucagon-like peptide-1 receptor, protein kinase A, and phosphatidylinositol-3 kinase inhibitors counteracted the anti-apoptotic effect of Exendin-4.Polyinosinic:polycytidylic acid transfection can mimic viral infection, and Exendin-4 exerted an anti-apoptotic effect both in MIN6 and insulin-producing cells from human induced pluripotent stem cells.

  15. Limiting influenza virus, HIV and dengue virus infection by targeting viral proteostasis

    Science.gov (United States)

    Heaton, Nicholas S.; Moshkina, Natasha; Fenouil, Romain; Gardner, Thomas J.; Aguirre, Sebastian; Shah, Priya S.; Zhao, Nan; Manganaro, Lara; Hultquist, Judd; Noel, Justine; Sachs, David; Hamilton, Jennifer; Leon, Paul E.; Chawdury, Amit; Tripathy, Shashank; Melegari, Camilla; Campisi, Laura; Hai, Rong; Metreveli, Giorgi; Gamarnik, Andrea V.; García-Sastre, Adolfo; Greenbaum, Benjamin; Simon, Viviana; Fernandez-Sesma, Ana; Krogan, Nevan; Mulder, Lubbertus C.F.; van Bakel, Harm; Tortorella, Domenico; Taunton, Jack; Palese, Peter; Marazzi, Ivan

    2016-01-01

    Viruses are obligate parasites as they require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy to suppress viral replication and a potential pan antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling, genetic, and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses, and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication we have identified targetable host factors for broad-spectrum antiviral therapies. PMID:26789921

  16. Reactive thrombocytosis in children with viral respiratory tract infections.

    Science.gov (United States)

    Haidopoulou, K; Goutaki, M; Lemonaki, M; Kavga, M; Papa, A

    2011-08-01

    Secondary thrombocytosis occurs commonly in children and is associated with a variety of lower respiratory tract infections, bacterial most often than viral. Aim of the study was to have an insight into the incidence and the clinical significance of thrombocytosis in children with lower respiratory tract infection caused by viral pathogens. Clinical data of 92 children, aged 10 days to 8 years, hospitalized with viral lower respiratory tract infection were studied retrospectively for presence of thrombocytosis (platelet count >500×109/l). Thrombocytosis was detected in 59.78% of patients. When children with and without thrombocytosis were compared a significant difference was found for age (P=0.002). We have found no differences among the two groups in sex, SaO2, clinical severity score and CRP levels at admission. Patients with RSV infection presented with significantly higher platelet counts (P=0.003). Extreme thrombocytosis (platelet count >1000×109/L) was noticed in eight patients (8.7%), seven of them were infants with RSV bronchiolitis. All children recovered uneventfully without requiring prophylaxis with anticoagulants or platelet aggregation inhibitors. Reactive thrombocytosis is a common finding in the acute care population of children hospitalized with viral lower respiratory tract infection. It represents a reactive phenomenon and does not indicate infection of bacterial cause or severe clinical course. Routine prophylactic antiplatelet treatment or further investigations are not necessary.

  17. FEATURES OF THE IMMUNE RESPONSE DURING VIRAL INFECTION

    Directory of Open Access Journals (Sweden)

    G. A. Borisov

    2015-01-01

    Full Text Available The aim of the investigation was to select using cluster analysis and comparatively characterize immune disorders types in acute and chronic viral infections. Patients with acute and chronic viral infections (n = 896 were examined: 77 patients with acute viral hepatitis B, 94 — chronic viral hepatitis B, 119 — chronic hepatitis C, 531 — recurrent herpes, 75 — human papillomavirus infection. Healthy persons (n = 466 were examined as control. The research of blood lymphocyte phenotype was performed by flow cytometry. Four-color immunophenotyping were used in the following panels: Т-lymphocytes (CD3+CD19–CD16/56–CD45+, Т-helpers (CD3+CD4+CD45+, cytotoxic Т-cells (CD3+CD8+CD45+, NKcells (CD3–CD16/56+CD45+, B-lymphocytes (CD3–CD19+CD16/56+CD45+. Absolute values were obtained on a dualplatform technology using the results of haematological analysis. The immunoglobulin concentrations were determined by ELISA. The clustering was performed by a single linkage method. The number of clusters was determined on the basis of calculating the values of the Euclidean distance between the mean group values. It was found that the parameters, characterizing the functional state of the various parts of the immune system in acute and chronic viral infections, considerable diversity values. Custer analysis allows to allocate 6 immunotypes defined different states of innate and adaptive immunity: characterized by activation of the innate (increasing the number of neutrophils and NK-cells and adaptive immunity humoral response (increasing the concentration of IgG, characterized by hyperreaction of adaptive immunity (a significant increase in the concentration of IgG, discoordinated (multidirectional changes in the values of immunological parameters, immunodeficiency and unresponsiveness (did not differ from the control parameters immunotypes. It is proved that in patients with viral infections most often determined by the

  18. NK cell subset redistribution during the course of viral infections

    Directory of Open Access Journals (Sweden)

    Enrico eLugli

    2014-08-01

    Full Text Available Natural killer (NK cells are important effectors of innate immunity that play a critical role in the control of human viral infections. Indeed, given their capability to directly recognize virally infected cells without the need of specific antigen presentation, NK cells are on the first line of defense against these invading pathogens. By establishing cellular networks with a variety of cell types such as dendritic cells, NK cells can also amplify anti-viral adaptive immune responses. In turn, viruses evolved and developed several mechanisms to evade NK cell-mediated immune activity. It has been reported that certain viral diseases, including human immunodeficiency virus-1 (HIV-1 as well as cytomegalovirus (CMV infections, are associated with a pathologic redistribution of NK cell subsets in the peripheral blood. In particular, it has been observed the expansion of unconventional CD56neg NK cells, whose effector functions are significantly impaired as compared to that of conventional CD56pos NK cells. In this review, we address the impact of chronic viral infections on the functional and phenotypic perturbations of human NK cell compartment.

  19. Viral infections as controlling factors for the deep biosphere? (Invited)

    Science.gov (United States)

    Engelen, B.; Engelhardt, T.; Sahlberg, M.; Cypionka, H.

    2009-12-01

    The marine deep biosphere represents the largest biotope on Earth. Throughout the last years, we have obtained interesting insights into its microbial community composition. However, one component that was completely overlooked so far is the viral inventory of deep-subsurface sediments. While viral infections were identified to have a major impact on the benthic microflora of deep-sea surface sediments (Danavaro et al. 2008), no studies were performed on deep-biosphere samples, so far. As grazers probably play only a minor role in anoxic and highly compressed deep sediments, viruses might be the main “predators” for indigenous microorganisms. Furthermore, the release of cell components, called “the viral shunt”, could have a major impact on the deep biosphere in providing labile organic compounds to non-infected microorganisms in these generally nutrient depleted sediments. However, direct counting of viruses in sediments is highly challenging due to the small size of viruses and the high background of small particles. Even molecular surveys using “universal” PCR primers that target phage-specific genes fail due to the vast phage diversity. One solution for this problem is the lysogenic viral life cycle as many bacteriophages integrate their DNA into the host genome. It is estimated that up to 70% of cultivated bacteria contain prophages within their genome. Therefore, culture collections (Batzke et al. 2007) represent an archive of the viral composition within the respective habitat. These prophages can be induced to become free phage particles in stimulation experiments in which the host cells are set under certain stress situations such as a treatment with UV exposure or DNA-damaging antibiotics. The study of the viral component within the deep biosphere offers to answer the following questions: To which extent are deep-biosphere populations controlled by viral infections? What is the inter- and intra-specific diversity and the host-specific viral

  20. Viral immunity. Transkingdom control of viral infection and immunity in the mammalian intestine.

    Science.gov (United States)

    Pfeiffer, Julie K; Virgin, Herbert W

    2016-01-15

    Viruses that infect the intestine include major human pathogens (retroviruses, noroviruses, rotaviruses, astroviruses, picornaviruses, adenoviruses, herpesviruses) that constitute a serious public health problem worldwide. These viral pathogens are members of a large, complex viral community inhabiting the intestine termed "the enteric virome." Enteric viruses have intimate functional and genetic relationships with both the host and other microbial constituents that inhabit the intestine, such as the bacterial microbiota, their associated phages, helminthes, and fungi, which together constitute the microbiome. Emerging data indicate that enteric viruses regulate, and are in turn regulated by, these other microbes through a series of processes termed "transkingdom interactions." This represents a changing paradigm in intestinal immunity to viral infection. Here we review recent advances in the field and propose new ways in which to conceptualize this important area.

  1. Transfusions of blood and blood products and viral infections

    Directory of Open Access Journals (Sweden)

    Marta Wróblewska

    2002-06-01

    Full Text Available Transfusions of blood and blood products are commonly used in medicine, but being biological materials they carry a risk of transmitting infections--viral, bacterial, parasitic, as well as prions. Laboratory tests used for screening of donated blood for viral infections at present cannot detect all infectious units. Criteria for selection of blood donors therefore must be very strict, while methods of inactivation of viruses and laboratory assays for detection of their presence must be improved. Indications for blood transfusion should be restricted.

  2. A method for quantifying mechanical properties of tissue following viral infection.

    Directory of Open Access Journals (Sweden)

    Vy Lam

    Full Text Available Viral infection and replication involves the reorganization of the actin network within the host cell. Actin plays a central role in the mechanical properties of cells. We have demonstrated a method to quantify changes in mechanical properties of fabricated model three-dimensional (3D connective tissue following viral infection. Using this method, we have characterized the impact of infection by the human herpesvirus, cytomegalovirus (HCMV. HCMV is a member of the herpesvirus family and infects a variety of cell types including fibroblasts. In the body, fibroblasts are necessary for maintaining connective tissue and function by creating mechanical force. Using this 3D connective tissue model, we observed that infection disrupted the cell's ability to generate force and reduced the cumulative contractile force of the tissue. The addition of HCMV viral particles in the absence of both viral gene expression and DNA replication was sufficient to disrupt tissue function. We observed that alterations of the mechanical properties are, in part, due to a disruption of the underlying complex actin microfilament network established by the embedded fibroblasts. Finally, we were able to prevent HCMV-mediated disruption of tissue function by the addition of human immune globulin against HCMV. This study demonstrates a method to quantify the impact of viral infection on mechanical properties which are not evident using conventional cell culture systems.

  3. Cellular Immune Responses and Viral Diversity in Individuals Treated during Acute and Early HIV-1 Infection

    Science.gov (United States)

    Altfeld, Marcus; Rosenberg, Eric S.; Shankarappa, Raj; Mukherjee, Joia S.; Hecht, Frederick M.; Eldridge, Robert L.; Addo, Marylyn M.; Poon, Samuel H.; Phillips, Mary N.; Robbins, Gregory K.; Sax, Paul E.; Boswell, Steve; Kahn, James O.; Brander, Christian; Goulder, Philip J.R.; Levy, Jay A.; Mullins, James I.; Walker, Bruce D.

    2001-01-01

    Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection. PMID:11148221

  4. Current approaches on viral infection: proteomics and functional validations

    Directory of Open Access Journals (Sweden)

    Jie eZheng

    2012-11-01

    Full Text Available Viruses could manipulate cellular machinery to ensure their continuous survival and thus become parasites of living organisms. Delineation of sophisticated host responses upon virus infection is a challenging task. It lies in identifying the repertoire of host factors actively involved in the viral infectious cycle and characterizing host responses qualitatively and quantitatively during viral pathogenesis. Mass spectrometry based proteomics could be used to efficiently study pathogen-host interactions and virus-hijacked cellular signaling pathways. Moreover, direct host and viral responses upon infection could be further investigated by activity based functional validation studies. These approaches involve drug inhibition of secretory pathway, immunofluorescence staining, dominant negative mutation of protein target, real time PCR, small interfering siRNA-mediated knockdown, and molecular cloning studies. In this way, functional validation could gain novel insights into the high-content proteomic dataset in an unbiased and comprehensive way.

  5. Rapid, targeted and culture-free viral infectivity assay in drop-based microfluidics.

    Science.gov (United States)

    Tao, Ye; Rotem, Assaf; Zhang, Huidan; Chang, Connie B; Basu, Anindita; Kolawole, Abimbola O; Koehler, Stephan A; Ren, Yukun; Lin, Jeffrey S; Pipas, James M; Feldman, Andrew B; Wobus, Christiane E; Weitz, David A

    2015-10-07

    A key viral property is infectivity, and its accurate measurement is crucial for the understanding of viral evolution, disease and treatment. Currently viral infectivity is measured using plaque assays, which involve prolonged culturing of host cells, and whose measurement is unable to differentiate between specific strains and is prone to low number fluctuation. We developed a rapid, targeted and culture-free infectivity assay using high-throughput drop-based microfluidics. Single infectious viruses are incubated in a large number of picoliter drops with host cells for one viral replication cycle followed by in-drop gene-specific amplification to detect infection events. Using murine noroviruses (MNV) as a model system, we measure their infectivity and determine the efficacy of a neutralizing antibody for different variants of MNV. Our results are comparable to traditional plaque-based assays and plaque reduction neutralization tests. However, the fast, low-cost, highly accurate genomic-based assay promises to be a superior method for drug screening and isolation of resistant viral strains. Moreover our technique can be adapted to measuring the infectivity of other pathogens, such as bacteria and fungi.

  6. Environmental modulation of mucosal immunity : Opportunities in respiratory viral infections

    NARCIS (Netherlands)

    Schijf, M.A.

    2013-01-01

    The exact cause of severe disease in children during primary RSV infections is not completely clear. There is a link with viral load, but differences virus strains do not seem to be the major reason why in some children the disease manifests as a mild cold while others suffer from a severe lower

  7. Quantum virology : improved management of viral infections through quantitative measurements

    NARCIS (Netherlands)

    Kalpoe, Jaijant Satishkumar

    2007-01-01

    Real-time monitoring of PCR has strongly supported the increased diagnostic use of nucleic acid detection assays in clinical virology. Particularly the improvements in the ability to quantify target nucleic acid sequences offer new opportunities in the management of viral infections. Real-time PCR

  8. Environmental modulation of mucosal immunity : Opportunities in respiratory viral infections

    NARCIS (Netherlands)

    Schijf, M.A.

    2013-01-01

    The exact cause of severe disease in children during primary RSV infections is not completely clear. There is a link with viral load, but differences virus strains do not seem to be the major reason why in some children the disease manifests as a mild cold while others suffer from a severe lower res

  9. Viral infections among couples for assisted reproduction in a fertility ...

    African Journals Online (AJOL)

    2012-09-28

    Sep 28, 2012 ... Nigerian Journal of Clinical Practice • Jul-Sep 2013 • Vol 16 • Issue 3 ... Aims: To assess the burden of viral infection among couples that present for ... Materials and Methods: Screening for HIV, hepatitis B virus (HBV) and ... Statistical analysis Used: Statistical Package for Social Sciences was employed.

  10. Prevalence and incidence of bloodborne viral infections among Danish prisoners

    NARCIS (Netherlands)

    Christensen, P B; Krarup, H B; Niesters, H G; Norder, H; Georgsen, J

    2000-01-01

    In order to determine the prevalence and incidence of bloodborne viral infections among prisoners, we conducted a prospective study in a Danish medium security prison for males. The prisoners were offered an interview and blood test for hepatitis and human immunodeficiency virus HIV at inclusion as

  11. Patterns of viral infection in honey bee queens

    DEFF Research Database (Denmark)

    Francis, Roy Mathew; Kryger, Per; Nielsen, Steen Lykke

    2013-01-01

    The well-being of a colony and replenishment of the workers depends on a healthy queen. Diseases in queens are seldom reported, and our knowledge on viral infection in queens is limited. In this study, 86 honey bee queens were collected from beekeepers in Denmark. All queens were tested separatel...

  12. ISG15 regulates peritoneal macrophages functionality against viral infection.

    Directory of Open Access Journals (Sweden)

    Emilio Yángüez

    Full Text Available Upon viral infection, the production of type I interferon (IFN and the subsequent upregulation of IFN stimulated genes (ISGs generate an antiviral state with an important role in the activation of innate and adaptive host immune responses. The ubiquitin-like protein (UBL ISG15 is a critical IFN-induced antiviral molecule that protects against several viral infections, but the mechanism by which ISG15 exerts its antiviral function is not completely understood. Here, we report that ISG15 plays an important role in the regulation of macrophage responses. ISG15-/- macrophages display reduced activation, phagocytic capacity and programmed cell death activation in response to vaccinia virus (VACV infection. Moreover, peritoneal macrophages from mice lacking ISG15 are neither able to phagocyte infected cells nor to block viral infection in co-culture experiments with VACV-infected murine embryonic fibroblast (MEFs. This phenotype is independent of cytokine production and secretion, but clearly correlates with impaired activation of the protein kinase AKT in ISG15 knock-out (KO macrophages. Altogether, these results indicate an essential role of ISG15 in the cellular immune antiviral response and point out that a better understanding of the antiviral responses triggered by ISG15 may lead to the development of therapies against important human pathogens.

  13. Dynamic Model Visualizing the Process of Viral Plaque Formation

    Directory of Open Access Journals (Sweden)

    Boriana Marintcheva

    2012-09-01

    Full Text Available In Microbiology and Virology courses, viral plaques are often presented to students as the way one can visualize viruses/bacteriophages. While students generally grasp the idea that counting plaques is essentially the same as counting viruses in their sample (assuming that one virus entering the cell is sufficient for productive infection, the process of plaque formation itself remains largely obscure. Many students fail to appreciate that viral plaques are actually a “laboratory-made” phenomenon allowing us to observe and study the growth of lytic viruses. The latter often presents a challenge for the interpretation of experimental data related to viral growth and drug discovery using plaque reduction assay. The hands-on model described here creates an opportunity for students to experience the process of viral plaque formation while engaging multiple senses and creating a lasting impression.  

  14. Twenty years of psychoneuroimmunology and viral infections in Brain, Behavior, and Immunity.

    Science.gov (United States)

    Bonneau, Robert H; Padgett, David A; Sheridan, John F

    2007-03-01

    For 20 years, Brain, Behavior, and Immunity has provided an important venue for the publication of studies in psychoneuroimmunology. During this time period, psychoneuroimmunology has matured into an important multidisciplinary science that has contributed significantly to our knowledge of mind, brain, and body interactions. This review will not only focus on the primary research papers dealing with psychoneuroimmunology, viral infections, and anti-viral vaccine responses in humans and animal models that have appeared on the pages of Brain, Behavior, and Immunity during the past 20 years, but will also outline a variety of strategies that could be used for expanding our understanding of the neuroimmune-viral pathogen relationship.

  15. The importance of lytic and nonlytic immune responses in viral infections

    DEFF Research Database (Denmark)

    Wodarz, Dominik; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2002-01-01

    Antiviral immune effector mechanisms can be divided broadly into lytic and nonlytic components. We use mathematical models to investigate the fundamental question of which type of response is required to combat different types of viral infection. According to our model, the relative roles...

  16. Innate immune responses of salmonid fish to viral infections.

    Science.gov (United States)

    Collet, Bertrand

    2014-04-01

    Viruses are the most serious pathogenic threat to the production of the main aquacultured salmonid species the rainbow trout Oncorhynchus mykiss and the Atlantic salmon Salmo salar. The viral diseases Infectious Pancreatic Necrosis (IPN), Pancreatic Disease (PD), Infectious Haemorrhagic Necrosis (IHN), Viral Haemorrhagic Septicaemia (VHS), and Infectious Salmon Anaemia (ISA) cause massive economic losses to the global salmonid aquaculture industry every year. To date, no solution exists to treat livestock affected by a viral disease and only a small number of efficient vaccines are available to prevent infection. As a consequence, understanding the host immune response against viruses in these fish species is critical to develop prophylactic and preventive control measures. The innate immune response represents an important part of the host defence mechanism preventing viral replication after infection. It is a fast acting response designed to inhibit virus propagation immediately within the host, allowing for the adaptive specific immunity to develop. It has cellular and humoral components which act in synergy. This review will cover inflammation responses, the cell types involved, apoptosis, antimicrobial peptides. Particular attention will be given to the type I interferon system as the major player in the innate antiviral defence mechanism of salmonids. Viral evasion strategies will also be discussed.

  17. [Liver transplantation in hepatitis B viral infection].

    Science.gov (United States)

    Kanizaj, Tajana Filipec; Colić-Cvrlje, Vesna; Mrzljak, Anna; Ostojić, Rajko

    2013-10-01

    Hepatitis B infection (HBV) causes liver cirrhosis and hepatocellular carcinoma that are indications for orthotopic liver transplantation (OLT). The outcome of OLT depends on the prevention of HBV reinfection and disease relapses. Out of 692 liver transplantations performed at Merkur University Hospital, 30 were done for HBV infection. These patients were treated with HBIG post OLT and lamivudine, entecavir, adefovir, tenofovir prior and post OLT. All patients became HBsAg and HBV DNA negative but four of them became HbsAg positive one year post OLT. The patients survived for 2 months to 7 years post OLT. With the introduction of HBIG immunoprophylaxis and new efficient antiviral treatment, the risk of relapse is only < 10%, and survival is the same as in other indications for OLT. Because of the high cost and long-term treatment, efforts have been made to prevent recurrent HBV disease by using the schedules according to pre- and post-transplant HBV viremia and introducing the new potent antiviral analogue nucleos(t)ides.

  18. Innate immune response to viral infection of the lungs.

    Science.gov (United States)

    See, Hayley; Wark, Peter

    2008-12-01

    Viral respiratory tract infections are the most common infectious illnesses, though they are usually self-limiting and confined to the respiratory tract. The rapid identification of viruses and their effective elimination with minimal local and systemic inflammation is a testament to the efficiency of the innate immune response within the airways and lungs. A failure of this response appears to occur in those with asthma and chronic obstructive pulmonary disease, where viral infection is an important trigger for acute exacerbations. The innate immune response to viruses requires their early detection through pathogen recognition receptors and the recruitment of the efficient antiviral response that is centred around the release of type 1 interferons. The airway epithelium provides both a barrier and an early detector for viruses, and interacts closely with cells of the innate immune response, especially macrophages and dendritic cells, to eliminate infection and trigger a specific adaptive immune response.

  19. Contrasting life strategies of viruses that infect photo- and heterotrophic bacteria, as revealed by viral tagging.

    Science.gov (United States)

    Deng, Li; Gregory, Ann; Yilmaz, Suzan; Poulos, Bonnie T; Hugenholtz, Philip; Sullivan, Matthew B

    2012-10-30

    Ocean viruses are ubiquitous and abundant and play important roles in global biogeochemical cycles by means of their mortality, horizontal gene transfer, and manipulation of host metabolism. However, the obstacles involved in linking viruses to their hosts in a high-throughput manner bottlenecks our ability to understand virus-host interactions in complex communities. We have developed a method called viral tagging (VT), which combines mixtures of host cells and fluorescent viruses with flow cytometry. We investigated multiple viruses which infect each of two model marine bacteria that represent the slow-growing, photoautotrophic genus Synechococcus (Cyanobacteria) and the fast-growing, heterotrophic genus Pseudoalteromonas (Gammaproteobacteria). Overall, viral tagging results for viral infection were consistent with plaque and liquid infection assays for cyanobacterial myo-, podo- and siphoviruses and some (myo- and podoviruses) but not all (four siphoviruses) heterotrophic bacterial viruses. Virus-tagged Pseudoalteromonas organisms were proportional to the added viruses under varied infection conditions (virus-bacterium ratios), while no more than 50% of the Synechococcus organisms were virus tagged even at viral abundances that exceeded (5 to 10×) that of their hosts. Further, we found that host growth phase minimally impacts the fraction of virus-tagged Synechococcus organisms while greatly affecting phage adsorption to Pseudoalteromonas. Together these findings suggest that at least two contrasting viral life strategies exist in the oceans and that they likely reflect adaptation to their host microbes. Looking forward to the point at which the virus-tagging signature is well understood (e.g., for Synechococcus), application to natural communities should begin to provide population genomic data at the proper scale for predictively modeling two of the most abundant biological entities on Earth. Viral study suffers from an inability to link viruses to hosts en

  20. Exosome Biogenesis, Regulation, and Function in Viral Infection.

    Science.gov (United States)

    Alenquer, Marta; Amorim, Maria João

    2015-09-17

    Exosomes are extracellular vesicles released upon fusion of multivesicular bodies(MVBs) with the cellular plasma membrane. They originate as intraluminal vesicles (ILVs) during the process of MVB formation. Exosomes were shown to contain selectively sorted functional proteins, lipids, and RNAs, mediating cell-to-cell communications and hence playing a role in the physiology of the healthy and diseased organism. Challenges in the field include the identification of mechanisms sustaining packaging of membrane-bound and soluble material to these vesicles and the understanding of the underlying processes directing MVBs for degradation or fusion with the plasma membrane. The investigation into the formation and roles of exosomes in viral infection is in its early years. Although still controversial, exosomes can, in principle, incorporate any functional factor, provided they have an appropriate sorting signal, and thus are prone to viral exploitation.This review initially focuses on the composition and biogenesis of exosomes. It then explores the regulatory mechanisms underlying their biogenesis. Exosomes are part of the endocytic system,which is tightly regulated and able to respond to several stimuli that lead to alterations in the composition of its sub-compartments. We discuss the current knowledge of how these changes affect exosomal release. We then summarize how different viruses exploit specific proteins of endocytic sub-compartments and speculate that it could interfere with exosome function, although no direct link between viral usage of the endocytic system and exosome release has yet been reported. Many recent reports have ascribed functions to exosomes released from cells infected with a variety of animal viruses, including viral spread, host immunity, and manipulation of the microenvironment, which are discussed. Given the ever-growing roles and importance of exosomes in viral infections, understanding what regulates their composition and levels, and

  1. Transmission of single and multiple viral variants in primary HIV-1 subtype C infection.

    Directory of Open Access Journals (Sweden)

    Vladimir Novitsky

    Full Text Available To address whether sequences of viral gag and env quasispecies collected during the early post-acute period can be utilized to determine multiplicity of transmitted HIV's, recently developed approaches for analysis of viral evolution in acute HIV-1 infection [1,2] were applied. Specifically, phylogenetic reconstruction, inter- and intra-patient distribution of maximum and mean genetic distances, analysis of Poisson fitness, shape of highlighter plots, recombination analysis, and estimation of time to the most recent common ancestor (tMRCA were utilized for resolving multiplicity of HIV-1 transmission in a set of viral quasispecies collected within 50 days post-seroconversion (p/s in 25 HIV-infected individuals with estimated time of seroconversion. The decision on multiplicity of HIV infection was made based on the model's fit with, or failure to explain, the observed extent of viral sequence heterogeneity. The initial analysis was based on phylogeny, inter-patient distribution of maximum and mean distances, and Poisson fitness, and was able to resolve multiplicity of HIV transmission in 20 of 25 (80% cases. Additional analysis involved distribution of individual viral distances, highlighter plots, recombination analysis, and estimation of tMRCA, and resolved 4 of the 5 remaining cases. Overall, transmission of a single viral variant was identified in 16 of 25 (64% cases, and transmission of multiple variants was evident in 8 of 25 (32% cases. In one case multiplicity of HIV-1 transmission could not be determined. In primary HIV-1 subtype C infection, samples collected within 50 days p/s and analyzed by a single-genome amplification/sequencing technique can provide reliable identification of transmission multiplicity in 24 of 25 (96% cases. Observed transmission frequency of a single viral variant and multiple viral variants were within the ranges of 64% to 68%, and 32% to 36%, respectively.

  2. Viral infection drives tissue fibrosis in vitro

    Directory of Open Access Journals (Sweden)

    Andrea P. Malizia

    2008-04-01

    Full Text Available Idiopathic Pulmonary Fibrosis (IPF is a refractory and lethal interstitial lung disease characterized by loss of alveolar epithelial cells, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. In this study we utilised a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV associated with lung fibrosis. A549 cells and an alveolar epithelial cell line infected with EBV (VAAK were used to identify genes whose expression was altered by EBV reactivation. EBV reactivation by TGFbeta1 drives alterations in expression of non-canonical Wnt pathway mediators, implicating it in epithelial mesenchymal transition (EMT, the molecular event underpinning scar production in tissue fibrosis. Cell invasion, EMT correlated transcripts expression, GSK-3b and c-Jun activation were altered in response to non-canonical Wnt pathway regulation. The role of EBV in promoting fibrosis can be attenuated by antiviral strategies and inhibition of Wnt signalling. Activation of non-canonical Wnt signalling pathway by EBV in epithelial cells suggests a novel mechanism of tissue fibrosis. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  3. Antiviral defense in shrimp: from innate immunity to viral infection.

    Science.gov (United States)

    Wang, Pei-Hui; Huang, Tianzhi; Zhang, Xiaobo; He, Jian-Guo

    2014-08-01

    The culture of penaeid shrimp is rapidly developing as a major business endeavor worldwide. However, viral diseases have caused huge economic loss in penaeid shrimp culture industries. Knowledge of shrimp innate immunity and antiviral responses has made important progress in recent years, allowing the design of better strategies for the prevention and control of shrimp diseases. In this study, we have updated information on shrimp antiviral immunity and interactions between shrimp hosts and viral pathogens. Current knowledge and recent progress in immune signaling pathways (e.g., Toll/IMD-NF-κB and JAK-STAT signaling pathways), RNAi, phagocytosis, and apoptosis in shrimp antiviral immunity are discussed. The mechanism of viral infection in shrimp hosts and the interactions between viruses and shrimp innate immune systems are also analyzed.

  4. Drosophila Adaptation to Viral Infection through Defensive Symbiont Evolution

    Science.gov (United States)

    Faria, Vitor G.; Magalhães, Sara; Paulo, Tânia F.; Nolte, Viola; Schlötterer, Christian

    2016-01-01

    Microbial symbionts can modulate host interactions with biotic and abiotic factors. Such interactions may affect the evolutionary trajectories of both host and symbiont. Wolbachia protects Drosophila melanogaster against several viral infections and the strength of the protection varies between variants of this endosymbiont. Since Wolbachia is maternally transmitted, its fitness depends on the fitness of its host. Therefore, Wolbachia populations may be under selection when Drosophila is subjected to viral infection. Here we show that in D. melanogaster populations selected for increased survival upon infection with Drosophila C virus there is a strong selection coefficient for specific Wolbachia variants, leading to their fixation. Flies carrying these selected Wolbachia variants have higher survival and fertility upon viral infection when compared to flies with the other variants. These findings demonstrate how the interaction of a host with pathogens shapes the genetic composition of symbiont populations. Furthermore, host adaptation can result from the evolution of its symbionts, with host and symbiont functioning as a single evolutionary unit. PMID:27684942

  5. DMPD: Toll-like receptors regulation of viral infection and disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18280610 Toll-like receptors regulation of viral infection and disease. Thompson JM...how Toll-like receptors regulation of viral infection and disease. PubmedID 18280610 Title Toll-like recepto...rs regulation of viral infection and disease. Authors Thompson JM, Iwasaki A. Pub

  6. INADEQUATE ANTIBODY-RESPONSE AGAINST RESPIRATORY VIRAL-INFECTION IN LONG-SURVIVING RAT LUNG ALLOGRAFTS

    NARCIS (Netherlands)

    WINTER, JB; GROEN, M; VANDERLOGT, K; WILDEVUUR, CRH; PROP, J

    1995-01-01

    Lung transplant recipients suffer from a high number of viral infections. It has been suggested that the defense against viral infections is impaired in lung transplants, Therefore, we investigated in rat lung transplants whether antibody responses against an intrapulmonary viral infection were impa

  7. Exosome Biogenesis, Regulation, and Function in Viral Infection

    Directory of Open Access Journals (Sweden)

    Marta Alenquer

    2015-09-01

    Full Text Available Exosomes are extracellular vesicles released upon fusion of multivesicular bodies(MVBs with the cellular plasma membrane. They originate as intraluminal vesicles (ILVs duringthe process of MVB formation. Exosomes were shown to contain selectively sorted functionalproteins, lipids, and RNAs, mediating cell-to-cell communications and hence playing a role in thephysiology of the healthy and diseased organism. Challenges in the field include the identificationof mechanisms sustaining packaging of membrane-bound and soluble material to these vesicles andthe understanding of the underlying processes directing MVBs for degradation or fusion with theplasma membrane. The investigation into the formation and roles of exosomes in viral infection is inits early years. Although still controversial, exosomes can, in principle, incorporate any functionalfactor, provided they have an appropriate sorting signal, and thus are prone to viral exploitation.This review initially focuses on the composition and biogenesis of exosomes. It then explores theregulatory mechanisms underlying their biogenesis. Exosomes are part of the endocytic system,which is tightly regulated and able to respond to several stimuli that lead to alterations in thecomposition of its sub-compartments. We discuss the current knowledge of how these changesaffect exosomal release. We then summarize how different viruses exploit specific proteins ofendocytic sub-compartments and speculate that it could interfere with exosome function, althoughno direct link between viral usage of the endocytic system and exosome release has yet beenreported. Many recent reports have ascribed functions to exosomes released from cells infectedwith a variety of animal viruses, including viral spread, host immunity, and manipulation of themicroenvironment, which are discussed. Given the ever-growing roles and importance of exosomesin viral infections, understanding what regulates their composition and levels, and

  8. Aptamers in Diagnostics and Treatment of Viral Infections

    Directory of Open Access Journals (Sweden)

    Tomasz Wandtke

    2015-02-01

    Full Text Available Aptamers are in vitro selected DNA or RNA molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. They have been conducted through the process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment. It serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. Properties of aptamers allow detecting virus infected cells or viruses themselves and make them competitive to monoclonal antibodies. Specific aptamers can be used to interfere in each stage of the viral replication cycle and also inhibit its penetration into cells. Many current studies have reported possible application of aptamers as a treatment or diagnostic tool in viral infections, e.g., HIV (Human Immunodeficiency Virus, HBV (Hepatitis B Virus, HCV (Hepatitis C Virus, SARS (Severe Acute Respiratory Syndrome, H5N1 avian influenza and recently spread Ebola. This review presents current developments of using aptamers in the diagnostics and treatment of viral diseases.

  9. HLA-KIR Interactions and Immunity to Viral Infections

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    Masoud Sabouri Ghannad

    2014-02-01

    Full Text Available Host genetic factors play a central role in determining the clinical phenotype of human diseases. Association between two polymorphic loci in human genome, human leukocyte antigen (HLA and killer cell immunoglobulin-like receptors (KIRs, and genetically complex infectious disease, particularly those of viral etiology, have been historically elusive. Hence, defining the influence of genetic diversity in HLA and KIRs on the outcome of viral infections has been extensively started in clinically well-defined cohort studies. HLA genes encode molecules which present antigenic peptide fragments to T lymphocytes as central players in adaptive immunity against infectious diseases. KIRs are expressed on natural killer cells which perform a crucial role in innate immunity to pathogen infection. The effector functions of NK cells such as direct killing of infected cells, cytokine production, and cross-talk with adaptive immune system depend on activation of NK cells, which is determined by their surface receptors. Among these receptors, KIRs, which interact with HLA class I, are mainly inhibitory and exhibit substantial genetic diversity. An extensive body of association studies indicates a role for HLA–KIRs interactions in infectious diseases, autoimmune disorders, cancer, transplantation, and reproduction. Various compound HLA-KIR genotypes appear to affect outcome of viral infections that suggests a role for HLA class I diversity in innate immunity as well as adaptive immune responses. The aim of this review is focusing on the impact of HLA and KIR alleles and different combinations of these alleles on clinical outcome of viral diseases to validate this proof-of-concept with respect to the therapeutic interventions.

  10. Mathematical Modeling of Viral Zoonoses in Wildlife

    OpenAIRE

    2011-01-01

    Zoonoses are a worldwide public health concern, accounting for approximately 75% of human infectious diseases. In addition, zoonoses adversely affect agricultural production and wildlife. We review some mathematical models developed for the study of viral zoonoses in wildlife and identify areas where further modeling efforts are needed.

  11. P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Bo Liu

    2013-02-01

    Full Text Available Arthropod-borne pathogens account for millions of deaths each year. Understanding the genetic mechanisms controlling vector susceptibility to pathogens has profound implications for developing novel strategies for controlling insect-transmitted infectious diseases. The fact that many viruses carry genes that have anti-apoptotic activity has long led to the hypothesis that induction of apoptosis could be a fundamental innate immune response. However, the cellular mechanisms mediating the induction of apoptosis following viral infection remained enigmatic, which has prevented experimental verification of the functional significance of apoptosis in limiting viral infection in insects. In addition, studies with cultured insect cells have shown that there is sometimes a lack of apoptosis, or the pro-apoptotic response happens relatively late, thus casting doubt on the functional significance of apoptosis as an innate immunity. Using in vivo mosquito models and the native route of infection, we found that there is a rapid induction of reaper-like pro-apoptotic genes within a few hours following exposure to DNA or RNA viruses. Recapitulating a similar response in Drosophila, we found that this rapid induction of apoptosis requires the function of P53 and is mediated by a stress-responsive regulatory region upstream of reaper. More importantly, we showed that the rapid induction of apoptosis is responsible for preventing the expression of viral genes and blocking the infection. Genetic changes influencing this rapid induction of reaper-like pro-apoptotic genes led to significant differences in susceptibility to viral infection.

  12. Final Technical Report: Viral Infection of Subsurface Microorganisms and Metal/Radionuclide Transport

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Karrie A.; Bender, Kelly S.; Li, Yusong

    2013-09-28

    Microbially mediated metabolisms have been identified as a significant factor either directly or indirectly impacting the fate and transport of heavy metal/radionuclide contaminants. To date microorganisms have been isolated from contaminated environments. Examination of annotated finished genome sequences of many of these subsurface isolates from DOE sites, revealed evidence of prior viral infection. To date the role that viruses play influencing microbial mortality and the resulting community structure which directly influences biogeochemical cycling in soils and sedimentary environments remains poorly understood. The objective of this exploratory study was to investigate the role of viral infection of subsurface bacteria and the formation of contaminant-bearing viral particles. This objective was approached by examining the following working hypotheses: (i) subsurface microorganisms are susceptible to viral infections by the indigenous subsurface viral community, and (ii) viral surfaces will adsorb heavy metals and radionuclides. Our results have addressed basic research needed to accomplish the BER Long Term Measure to provide sufficient scientific understanding such that DOE sites would be able to incorporate coupled physical, chemical and biological processes into decision making for environmental remediation or natural attenuation and long-term stewardship by establishing viral-microbial relationships on the subsequent fate and transport of heavy metals and radionuclides. Here we demonstrated that viruses play a significant role in microbial mortality and community structure in terrestrial subsurface sedimentary systems. The production of viral-like particles within subsurface sediments in response to biostimulation with dissolved organic carbon and a terminal electron acceptor resulted in the production of viral-like particles. Organic carbon alone did not result in significant viral production and required the addition of a terminal electron acceptor

  13. Mixed Viral Infections Circulating in Hospitalized Patients with Respiratory Tract Infections in Kuwait

    Directory of Open Access Journals (Sweden)

    Sahar Essa

    2015-01-01

    Full Text Available The aim of this study was to determine the frequency of viral mixed detection in hospitalized patients with respiratory tract infections and to evaluate the correlation between viral mixed detection and clinical severity. Hospitalized patients with respiratory tract infections (RTI were investigated for 15 respiratory viruses by using sensitive molecular techniques. In total, 850 hospitalized patients aged between 3 days and 80 years were screened from September 2010 to April 2014. Among the 351 (47.8% patients diagnosed with viral infections, viral mixed detection was identified in 49 patients (14%, with human rhinovirus (HRV being the most common virus associated with viral mixed detection (7.1%, followed by adenovirus (AdV (4% and human coronavirus-OC43 (HCoV-OC43 (3.7%. The highest combination of viral mixed detection was identified with HRV and AdV (2%, followed by HRV and HCoV-OC43 (1.4%. Pneumonia and bronchiolitis were the most frequent reason for hospitalization with viral mixed detection (9.1%. There were statistical significance differences between mixed and single detection in patients diagnosed with bronchiolitis (P=0.002 and pneumonia (P=0.019. Our findings might indicate a significant association between respiratory virus mixed detection and the possibility of developing more severe LRTI such as bronchiolitis and pneumonia when compared with single detection.

  14. Frequency dependence and viral diversity imply chaos in an HIV model

    Science.gov (United States)

    Iwami, Shingo; Nakaoka, Shinji; Takeuchi, Yasuhiro

    2006-11-01

    In this paper, we consider the effect of viral diversity on the human immune system with frequency dependent rate of proliferation of CTLs (cytotoxic T-lymphocytes) and rate of elimination of infected cells by CTLs. We show that the interior equilibrium of our model can become unstable without viral diversity and we observe stable periodic orbits. Furthermore, our mathematical models suggest that viral diversity produces strange attractors.

  15. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection

    Directory of Open Access Journals (Sweden)

    Jeyaseelan Nadarajah

    2015-01-01

    Full Text Available Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made.

  16. Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins.

    Directory of Open Access Journals (Sweden)

    Ekaterina Dadachova

    2006-11-01

    Full Text Available BACKGROUND: The HIV epidemic is a major threat to health in the developing and western worlds. A modality that targets and kills HIV-1-infected cells could have a major impact on the treatment of acute exposure and the elimination of persistent reservoirs of infected cells. The aim of this proof-of-principle study was to demonstrate the efficacy of a therapeutic strategy of targeting and eliminating HIV-1-infected cells with radiolabeled antibodies specific to viral proteins in vitro and in vivo. METHODS AND FINDINGS: Antibodies to HIV-1 envelope glycoproteins gp120 and gp41 labeled with radioisotopes bismuth 213 ((213Bi and rhenium 188 ((188Re selectively killed chronically HIV-1-infected human T cells and acutely HIV-1-infected human peripheral blood mononuclear cells (hPBMCs in vitro. Treatment of severe combined immunodeficiency (SCID mice harboring HIV-1-infected hPBMCs in their spleens with a (213Bi- or (188Re-labeled monoclonal antibody (mAb to gp41 resulted in a 57% injected dose per gram uptake of radiolabeled mAb in the infected spleens and in a greater than 99% elimination of HIV-1-infected cells in a dose-dependent manner. The number of HIV-1-infected thymocytes decreased 2.5-fold in the human thymic implant grafts of SCID mice treated with the (188Re-labeled antibody to gp41 compared with those treated with the (188Re-control mAb. The treatment did not cause acute hematologic toxicity in the treated mice. CONCLUSIONS: The current study demonstrates the effectiveness of HIV-targeted radioimmunotherapy and may provide a novel treatment option in combination with highly active antiretroviral therapy for the eradication of HIV.

  17. Massive activation of archaeal defense genes during viral infection

    NARCIS (Netherlands)

    Quax, T.E.F.; Voet, M.; Sismeiro, O.; Dillies, M.A.; Jagla, B.; Coppée, J.Y.; Sezonov, G.; Forterre, P.; Oost, van der J.; Lavigne, R.; Prangishvili, D.

    2013-01-01

    Archaeal viruses display unusually high genetic and morphological diversity. Studies of these viruses proved to be instrumental for the expansion of knowledge on viral diversity and evolution. The Sulfolobus islandicus rod-shaped virus 2 (SIRV2) is a model to study virus-host interactions in Archaea

  18. Association between high nasopharyngeal viral load and disease severity in children with human metapneumovirus infection

    NARCIS (Netherlands)

    Bosis, Samantha; Esposito, Susanna; Osterhaus, Albert D. M. E.; Tremolati, Elena; Begliatti, Enrica; Tagliabue, Claudia; Corti, Fabiola; Principi, Nicola; Niesters, Hubert G. M.

    Background: Previous studies have shown that viral genotype and viral load may play a significant role in the pathogenesis of viral infections. Objectives: The aim of this study was to evaluate these aspects of hMPV infections in children and their household contacts. Study design: Between I

  19. Infections in hemodialysis: a concise review. Part II: blood transmitted viral infections

    Science.gov (United States)

    Eleftheriadis, T; Liakopoulos, V; Leivaditis, K; Antoniadi, G; Stefanidis, I

    2011-01-01

    Hemodialysis (HD) patients are particularly predisposed to infections. It seems that the HD procedure per se as well as disturbances in both innate and adaptive immunity significantly contribute to this susceptibility. Infections are the major cause of morbidity and the second cause of death following cardiovascular events in HD patients. Episodes of bacteremia and pneumonia account for the majority of severe infections in this population. In addition to these bacterial infections another common problem in HD units is the blood transmitted viral infections, particularly infections caused by hepatitis B virus, hepatitis C virus and Human immunodeficiency virus. A number of safety concerns exist for limiting the spread of these viral infections among HD patients and the staff of the unit. The aim of the present review is to present in a concise albeit practical form the difficult aspect of infections in HD. For practical reasons the review is separated in two parts. The previous first part covered bacteremia and respiratory infections, while the present second part covers blood transmitted viral infections. PMID:22110292

  20. The herpes simplex virus host shutoff RNase degrades cellular and viral mRNAs made before infection but not viral mRNA made after infection.

    Science.gov (United States)

    Taddeo, Brunella; Zhang, Weiran; Roizman, Bernard

    2013-04-01

    A herpes simplex virus tegument protein brought into the cell during infection and designated the virion host shutoff protein (VHS) is an endoribonuclease that degrades mRNA. The prevailing view for many years has been that the VHS-RNase does not discriminate between cellular and viral RNAs and that the viruses prevail because the accumulation of viral transcripts outpaces their degradation. Here we report the following. (i) The degradation of viral mRNA made during infection of Vero or HEp-2 cells proceeds at a much-reduced rate compared to that of cellular mRNA. In effect, viral mRNAs are largely stable, whereas cellular mRNAs are rapidly degraded or, in the case of AU-rich mRNA, cleaved and rendered dysfunctional. (ii) In contrast to viral mRNAs made after infection, viral mRNAs expressed by plasmids transfected into cells prior to infection are degraded after infection at a rate comparable to that of cellular mRNAs. Moreover, the mRNA encoded by the transfected plasmid is hyperadenylated in the infected cell. Hyperadenylation but not degradation of mRNAs is blocked by actinomycin D. The results indicate that VHS-mRNA discriminates between viral and cellular mRNA but only in the context of infection and that discrimination is not based on the sequence of the mRNA but most likely on one or more viral factors expressed in the infected cell.

  1. The type I interferon response during viral infections: a "SWOT" analysis.

    Science.gov (United States)

    Gaajetaan, Giel R; Bruggeman, Cathrien A; Stassen, Frank R

    2012-03-01

    The type I interferon (IFN) response is a strong and crucial moderator for the control of viral infections. The strength of this system is illustrated by the fact that, despite some temporary discomfort like a common cold or diarrhea, most viral infections will not cause major harm to the healthy immunocompetent host. To achieve this, the immune system is equipped with a wide array of pattern recognition receptors and the subsequent coordinated type I IFN response orchestrated by plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs). The production of type I IFN subtypes by dendritic cells (DCs), but also other cells is crucial for the execution of many antiviral processes. Despite this coordinated response, morbidity and mortality are still common in viral disease due to the ability of viruses to exploit the weaknesses of the immune system. Viruses successfully evade immunity and infection can result in aberrant immune responses. However, these weaknesses also open opportunities for improvement via clinical interventions as can be seen in current vaccination and antiviral treatment programs. The application of IFNs, Toll-like receptor ligands, DCs, and antiviral proteins is now being investigated to further limit viral infections. Unfortunately, a common threat during stimulation of immunity is the possible initiation or aggravation of autoimmunity. Also the translation from animal models to the human situation remains difficult. With a Strengths-Weaknesses-Opportunities-Threats ("SWOT") analysis, we discuss the interaction between host and virus as well as (future) therapeutic options, related to the type I IFN system.

  2. Viral infection and innate pattern recognition receptors in induction of Hashimoto's thyroiditis.

    Science.gov (United States)

    Morohoshi, Kazuki; Takahashi, Yurie; Mori, Kouki

    2011-12-01

    Hashimoto's thyroiditis, a common organ-specific autoimmune disease, is multifactorial in which both genetic susceptibility and environmental factors including infection play a critical role in its pathogenesis. Viral infection activates both the innate and adaptive immunity and is implicated as a trigger of Hashimoto's thyroiditis. Candidate viruses include hepatitis C virus and human parvovirus B19. Viral components, which are recognized by innate receptors including Toll-like receptors (TLRs), are detected in thyroid tissues and sera of patients with Hashimoto's thyroiditis. While conflicting results have been obtained regarding the role of TLRs in autoimmune diseases, our preliminary study suggested a contribution of TLR2 and dectin-1 in combination, TLR4, or TLR7 to the production of anti-thyroglobulin antibody in nonobese diabetic mice, a mouse model of Hashimoto's thyroiditis. Despite interesting circumstantial evidence, however, whether viral infection and innate receptors are involved in the development of Hashimoto's thyroiditis remains largely unclear. In this review, we summarize our knowledge regarding the role of viral infection and innate receptors in the etiology of Hashimoto's thyroiditis.

  3. Immune biomarkers predictive of respiratory viral infection in elderly nursing home residents.

    Directory of Open Access Journals (Sweden)

    Jennie Johnstone

    Full Text Available OBJECTIVE: To determine if immune phenotypes associated with immunosenescence predict risk of respiratory viral infection in elderly nursing home residents. METHODS: Residents ≥ 65 years from 32 nursing homes in 4 Canadian cities were enrolled in Fall 2009, 2010 and 2011, and followed for one influenza season. Following influenza vaccination, peripheral blood mononuclear cells (PBMCs were obtained and analysed by flow cytometry for T-regs, CD4+ and CD8+ T-cell subsets (CCR7+CD45RA+, CCR7-CD45RA+ and CD28-CD57+ and CMV-reactive CD4+ and CD8+ T-cells. Nasopharyngeal swabs were obtained and tested for viruses in symptomatic residents. A Cox proportional hazards model adjusted for age, sex and frailty, determined the relationship between immune phenotypes and time to viral infection. RESULTS: 1072 residents were enrolled; median age 86 years and 72% female. 269 swabs were obtained, 87 were positive for virus: influenza (24%, RSV (14%, coronavirus (32%, rhinovirus (17%, human metapneumovirus (9% and parainfluenza (5%. In multivariable analysis, high T-reg% (HR 0.41, 95% CI 0.20-0.81 and high CMV-reactive CD4+ T-cell% (HR 1.69, 95% CI 1.03-2.78 were predictive of respiratory viral infection. CONCLUSIONS: In elderly nursing home residents, high CMV-reactive CD4+ T-cells were associated with an increased risk and high T-regs were associated with a reduced risk of respiratory viral infection.

  4. Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

    Directory of Open Access Journals (Sweden)

    Karl J Staples

    Full Text Available Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

  5. VIRAL ETIOLOGY ACUTE INTESTINAL INFECTIONS MOLECULAR MONITORING IN CHILDREN’S HOSPITAL

    OpenAIRE

    A. V. Sergeeva; L. Y. Poslova; O. V. Kovalishena; A. S. Blagonravova; N. V. Epifanova; T. A. Sashina; Morozova, O.V.; N. A. Novikova

    2015-01-01

    On the territory of the Russian Federation in the overall structure of acute intestinal infections the proportion of viral diarrhea among children varies from 24 to 78% of cases depending on the season. The acute viral intestinal infections etiological confirmation is performed mainly among patients of infectious hospitals. The prevalence of viral acute intestinal infections in non-infectious hospitals, including infections associated with medical care, remains unclear. Currently estimation o...

  6. RNA interference strategies as therapy for respiratory viral infections.

    Science.gov (United States)

    DeVincenzo, John P

    2008-10-01

    RNA interference (RNAi) is a recently discovered, naturally occurring intracellular process that regulates gene expression through the silencing of specific mRNAs. Methods of harnessing this natural pathway are being developed that allow the catalytic degradation of targeted mRNAs using specifically designed complementary small-interfering RNAs (siRNA). siRNAs are being chemically modified to acquire drug-like properties. Numerous recent high profile publications have provided proofs of concept that RNAi may be of therapeutic use. Much of the design of these siRNAs can be accomplished bioinformatically, thus potentially expediting drug discovery and opening new avenues of therapy for many uncommon, orphan, or emerging diseases. Although endogenous human disease targets can theoretically be affected by RNAi therapeutics, nonendogenous targets (eg, viral targets) are attractive and RNAi therapeutics have been shown to act as antivirals in vivo and in vitro. Respiratory viral infections are particularly attractive targets for RNAi therapeutics because the infected cells exist at the air-lung interface, thereby positioning these cells to be accessible to topical administration of siRNA, for example by aerosol. RNAi therapeutics have been shown to be active against respiratory syncytial virus, parainfluenza and influenza in vitro and in vivo resulting in profound antiviral effects. The first RNAi therapeutic to be designed as an anti-infective medication has now entered proof of concept clinical trials in man. A discussion of the science behind RNAi is followed by a presentation of the potential practical issues in applying this technology to respiratory viral diseases. RNAi may offer new strategies for the treatment of respiratory syncytial virus and other respiratory viruses.

  7. Radiometric Methods for Rapid Diagnosis of Viral Infection.

    Science.gov (United States)

    2014-09-26

    6/ NL IL 1-2 1-N6 U..V. -- V-- 1** ’~r I Ii’sW - -Kw RADIOMETRIC METHODS FOR RAPID DIAGNOSIS OF VIRAL INFECTION o Annual Report Min-Fu Tsan, M.D...REPORT DATE Command November 22, 1976 *U. S.. Army Medical Research and Development/ 13 NUMBER OF P!AGES Fort Detrick, Frederick, MD1 21701,5012 21...by black number) , Radiometric methods Virus r; fV 20. AISSY fRACT (Continue on, reverse sie it nwc. urr and ldvntity by block nuaibe,) -Vrtwo

  8. [Progression of viral infection in twins born from a mother infected with human immunodeficiency virus].

    Science.gov (United States)

    Gaggero, A; Escanilla, D; Larrañaga, C; Uribe, P; Espejo, R

    1995-10-01

    We studied the evolution of HIV-1 infection and immune response during six years in two twins born from an infected mother. The children had a continuous progression of the infection, proved by CD4+ cell count, serum anti-HIV antibodies, cultivable virus and proviral load. Now, both children are on antiviral treatment. The analysis of serum antibodies showed a different immune response in both children. One of them developed higher levels of antibodies directed against viral proteins and synthetic peptides derived from their aminoacid sequence. In this child, the amount of cultivable virus increased less than in his twin. Nucleotide sequencing of a part of viral genoma, showed that the virus belonged to the B subtype, prevalent in America and Europe. The observed differences in viral sequences suggest a different selective pressure in both twins. This phenomenon could be related to the observed differences in immune response.

  9. The Role of IL-22 in Viral Infections: Paradigms and Paradoxes

    Directory of Open Access Journals (Sweden)

    Silvia eGimeno Brias

    2016-05-01

    Full Text Available Interleukin-22 (IL-22 is a member of the IL-10 family of cytokines. Hematopoietic cells express IL-22, and this cytokine signals through the heterodimeric IL-22R expressed by non-hematopoietic cells. A growing body of evidence points towards a role for IL-22 in a diverse array of biological functions ranging from cellular proliferation, tissue protection and regeneration, and inflammation. In recent years, the role that IL-22 plays in antiviral immune responses has been examined in a number of infection models. Herein, we assess our current understanding of how IL-22 determines the outcome of viral infections and define common mechanisms that are evident from, sometimes paradoxical, findings derived from these studies. Finally, we discuss the potential therapeutic utility of IL-22 manipulation in the treatment and prevention of viral infections and associated pathologies.

  10. Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.

    Science.gov (United States)

    Heaton, Nicholas S; Moshkina, Natasha; Fenouil, Romain; Gardner, Thomas J; Aguirre, Sebastian; Shah, Priya S; Zhao, Nan; Manganaro, Lara; Hultquist, Judd F; Noel, Justine; Sachs, David; Sachs, David H; Hamilton, Jennifer; Leon, Paul E; Chawdury, Amit; Tripathi, Shashank; Melegari, Camilla; Campisi, Laura; Hai, Rong; Metreveli, Giorgi; Gamarnik, Andrea V; García-Sastre, Adolfo; Greenbaum, Benjamin; Simon, Viviana; Fernandez-Sesma, Ana; Krogan, Nevan J; Mulder, Lubbertus C F; van Bakel, Harm; Tortorella, Domenico; Taunton, Jack; Palese, Peter; Marazzi, Ivan

    2016-01-19

    Viruses are obligate parasites and thus require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy hosts use to suppress viral replication and a potential pan-antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling and genetic and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication, we have identified targetable host factors for broad-spectrum antiviral therapies.

  11. Virally encoded chemokines and chemokine receptors in the role of viral infections

    DEFF Research Database (Denmark)

    Holst, Peter J; Lüttichau, Hans R; Schwartz, Thue W

    2003-01-01

    are the acquisition and modification of host-encoded chemokines and chemokine receptors. The described viral molecules leave nothing to chance and have thoroughly and efficiently corrupted the host immune system. Through this process viruses have identified key molecules in antiviral responses by their inhibition...... of these or potent ways to alter an efficient antiviral response to a weak Th2-driven response. Examples here are the chemokine scavenging by US28, attractance of Th2 cells and regulatory cells by vMIP1-3 and the selective engaging of CCR8 by MC148. Important insights into viral pathology and possible targets...... for antiviral therapies have been provided by UL33, UL78 and in particular ORF74 and the chances are that many more will follow. In HHV8 vMIP-2 and the chemokine-binding proteins potent anti-inflammatory agents have been provided. These have already had their potential demonstrated in animal models and may...

  12. Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy

    Directory of Open Access Journals (Sweden)

    Eliana C.A. Benites

    2014-07-01

    Full Text Available OBJECTIVE: to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI and/or fever. METHODS: cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc and University Hospital (HU, Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland, and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta for detection of influenza virus (H1N1, B, rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ2 or Fisher's exact test. RESULTS: 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3% was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%, respiratory syncytial virus AB (8.7%, and coronavirus (6.8%. Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7 were positive for viruses. There were no deaths. CONCLUSIONS: the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs.

  13. Amitraz and its metabolite modulate honey bee cardiac function and tolerance to viral infection.

    Science.gov (United States)

    O'Neal, Scott T; Brewster, Carlyle C; Bloomquist, Jeffrey R; Anderson, Troy D

    2017-10-01

    The health and survival of managed honey bee (Apis mellifera) colonies are affected by multiple factors, one of the most important being the interaction between viral pathogens and infestations of the ectoparasitic mite Varroa destructor. Currently, the only effective strategy available for mitigating the impact of viral infections is the chemical control of mite populations. Unfortunately, the use of in-hive acaricides comes at a price, as they can produce sublethal effects that are difficult to quantify, but may ultimately be as damaging as the mites they are used to treat. The goal of this study was to investigate the physiological and immunological effects of the formamidine acaricide amitraz and its primary metabolite in honey bees. Using flock house virus as a model for viral infection, this study found that exposure to a formamidine acaricide may have a negative impact on the ability of honey bees to tolerate viral infection. Furthermore, this work has demonstrated that amitraz and its metabolite significantly alter honey bee cardiac function, most likely through interaction with octopamine receptors. The results suggest a potential drawback to the in-hive use of amitraz and raise intriguing questions about the relationship between insect cardiac function and disease tolerance. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Polyphasic innate immune responses to acute and chronic LCMV infection: Innate immunity to acute & chronic viral infection

    OpenAIRE

    Norris, Brian A; Uebelhoer, Luke S.; Nakaya, Helder I.; Price, Aryn A; Grakoui, Arash; Pulendran, Bali

    2013-01-01

    Resolution of acute and chronic viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. Here we report that infection with acute Armstrong (ARM) or chronic Clone 13 (C13) strains of lymphocytic choriomeningitis virus (LCMV) led to two distinct phases of innate immune response. During the first 72hr of infection, dendritic cells upregulated activation markers, and stimulated anti-viral CD8+ T cells, independent of viral strain. Seven days after ...

  15. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia.

    Directory of Open Access Journals (Sweden)

    Yuly Andrea Remolina

    Full Text Available To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI admitted to sentinel surveillance institutions in Bogotá in 2012.A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained.Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia.Ninety-one adult patients with acute respiratory infection (55% were female.Viral identification, intensive care unit admission, hospital stay, and mortality.Viral identification was achieved for 63 patients (69.2%. Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients.The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality.

  16. Sensors of Infection: Viral Nucleic Acid PRRs in Fish

    Directory of Open Access Journals (Sweden)

    Sarah Poynter

    2015-07-01

    Full Text Available Viruses produce nucleic acids during their replication, either during genomic replication or transcription. These nucleic acids are present in the cytoplasm or endosome of an infected cell, or in the extracellular space to be sensed by neighboring cells during lytic infections. Cells have mechanisms of sensing virus-generated nucleic acids; these nucleic acids act as flags to the cell, indicating an infection requiring defense mechanisms. The viral nucleic acids are called pathogen-associated molecular patterns (PAMPs and the sensors that bind them are called pattern recognition receptors (PRRs. This review article focuses on the most recent findings regarding nucleic acids PRRs in fish, including: Toll-like receptors (TLRs, RIG-I-like receptors (RLRs, cytoplasmic DNA sensors (CDSs and class A scavenger receptors (SR-As. It also discusses what is currently known of the downstream signaling molecules for each PRR family and the resulting antiviral response, either type I interferons (IFNs or pro-inflammatory cytokine production. The review highlights what is known but also defines what still requires elucidation in this economically important animal. Understanding innate immune systems to virus infections will aid in the development of better antiviral therapies and vaccines for the future.

  17. Aberrant CD8+ T-Cell Responses and Memory Differentiation upon Viral Infection of an Ataxia-Telangiectasia Mouse Model Driven by Hyper-Activated Akt and mTORC1 Signaling

    Science.gov (United States)

    D'Souza, Anthony D.; Parish, Ian A.; McKay, Sharen E.; Kaech, Susan M.; Shadel, Gerald S.

    2011-01-01

    Immune system-related pathology is common in ataxia-telangiectasia (A-T) patients and mice that lack the protein kinase, A-T mutated (ATM). However, it has not been studied how ATM influences immune responses to a viral infection. Using the lymphocytic choriomeningitis virus (LCMV) infection model, we show that ATM−/− mice, despite having fewer naïve CD8+ T cells, effectively clear the virus. However, aberrant CD8+ T-cell responses are observed, including defective expansion and contraction, effector-to-memory differentiation, and a switch in viral-epitope immunodominance. T-cell receptor-activated, but not naïve, ATM−/− splenic CD8+ T cells have increased ribosomal protein S6 and Akt phosphorylation and do not proliferate well in response to IL-15, a cytokine important for memory T-cell development. Accordingly, pharmacological Akt or mammalian target of rapamycin complex 1 (mTORC1) inhibition during T-cell receptor activation alone rescues the IL-15 proliferation defect. Finally, rapamycin treatment during LCMV infection in vivo increases the number of memory T cells in ATM−/− mice. Altogether, these results show that CD8+ T cells lacking ATM have hyperactive Akt and mTORC1 signaling in response to T-cell receptor activation, which results in aberrant cytokine responses and memory T-cell development. We speculate that similar signaling defects contribute to the immune system pathology of A-T, and that inhibition of Akt and/or mTORC1 may be of therapeutic value. PMID:21641396

  18. Foxp3+ regulatory T cells control persistence of viral CNS infection.

    Directory of Open Access Journals (Sweden)

    Dajana Reuter

    Full Text Available We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified mice and recombinant measles virus (MV. Using this model infection we investigated the role of regulatory T cells (Tregs as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+ CD25(+ Foxp3(+ Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+ T cells predominantly recognising the H-2D(b-presented viral hemagglutinin epitope MV-H(22-30 (RIVINREHL were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p. application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT in DEREG (depletion of regulatory T cells-mice induced an increase of virus-specific CD8(+ effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.

  19. Human immunodeficiency virus type 1 infection of human uterine epithelial cells: viral shedding and cell contact-mediated infectivity.

    Science.gov (United States)

    Asin, Susana N; Wildt-Perinic, Dunja; Mason, Sarah I; Howell, Alexandra L; Wira, Charles R; Fanger, Michael W

    2003-05-15

    We examined the mechanism of human immunodeficiency virus (HIV) type 1 infection of human uterine epithelial cells to gain a clearer understanding of the events by which HIV-1 infects cells within the female reproductive tract. We demonstrated that these cells can be productively infected by HIV-1 and that infection is associated with viral RNA reverse transcription, DNA transcription, and secretion of infectious virus. Levels of viral DNA and secreted virus decreased gradually after infection. Moreover, virus released by the uterine epithelial cells shortly after infection was able to infect human T cell lines, but virus released later did not. In contrast, human CD4(+) T cell lines were infected after cocultivation with epithelial cells at both early and late stages of infection. These data demonstrated that HIV-1 infects human epithelial cells of upper reproductive tract origin and that productive viral infection of epithelial cells may be an important mechanism of transmission of HIV-1 infection in women.

  20. Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients▿

    Science.gov (United States)

    Soares, Rui S.; Tendeiro, Rita; Foxall, Russell B.; Baptista, António P.; Cavaleiro, Rita; Gomes, Perpétua; Camacho, Ricardo; Valadas, Emília; Doroana, Manuela; Lucas, Margarida; Antunes, Francisco; Victorino, Rui M. M.; Sousa, Ana E.

    2011-01-01

    Viremia is significantly lower in HIV-2 than in HIV-1 infection, irrespective of disease stage. Nevertheless, the comparable proviral DNA burdens observed for these two infections indicate similar numbers of infected cells. Here we investigated this apparent paradox by assessing cell-associated viral replication. We found that untreated HIV-1-positive (HIV-1+) and HIV-2+ individuals, matched for CD4 T cell depletion, exhibited similar gag mRNA levels, indicating that significant viral transcription is occurring in untreated HIV-2+ patients, despite the reduced viremia (undetectable to 2.6 × 104 RNA copies/ml). However, tat mRNA transcripts were observed at significantly lower levels in HIV-2+ patients, suggesting that the rate of de novo infection is decreased in these patients. Our data also reveal a direct relationship of gag and tat transcripts with CD4 and CD8 T cell activation, respectively. Antiretroviral therapy (ART)-treated HIV-2+ patients showed persistent viral replication, irrespective of plasma viremia, possibly contributing to the emergence of drug resistance mutations, persistent hyperimmune activation, and poor CD4 T cell recovery that we observed with these individuals. In conclusion, we provide here evidence of significant ongoing viral replication in HIV-2+ patients, further emphasizing the dichotomy between amount of plasma virus and cell-associated viral burden and stressing the need for antiretroviral trials and the definition of therapeutic guidelines for HIV-2 infection. PMID:21159859

  1. Hepatitis C viral infection as an associated risk factor for necrotizing fasciitis.

    Science.gov (United States)

    Scher, Danielle; Kanlic, Enes; Bader, Julia; Ortiz, Melchor; Abdelgawad, Amr

    2012-04-01

    Necrotizing fasciitis is a rare soft tissue infection associated with a high mortality rate. Several risk factors for the development of necrotizing fasciitis have been studied, which has given surgeons insight into the types of patients who are more likely to present with this rapidly progressive infection. The concomitant diagnosis of hepatitis C viral infection has not been reported in the literature previously. In this retrospective study covering a 12-year period in 1 Level I trauma center, 10 (34%) of 29 patients presenting with necrotizing fasciitis had an underlying diagnosis of hepatitis C viral infection. The mortality rate in patients with hepatitis C viral infection was 30% compared with 21% for those without hepatitis C viral infection (P=.59). The proportion of patients presenting with the concomitant diagnosis of hepatitis C viral infection and necrotizing fasciitis was statistically greater than that expected from the prevalence of hepatitis C viral infection in the general population (1.8%; Pnecrotizing fasciitis. Although our sample size was too small to show a statistical significance, we believe that a clinically significant increase in mortality of necrotizing fasciitis occurred in patients with concomitant hepatitis C viral infection. Therefore, the presence of hepatitis C viral infection in patients presenting with symptoms of necrotizing fasciitis should raise the clinical suspicion for this diagnosis, with the potential for a worse prognosis.

  2. Viral vector vaccines protect cockatiels from inflammatory lesions after heterologous parrot bornavirus 2 challenge infection.

    Science.gov (United States)

    Runge, Solveig; Olbert, Marita; Herden, Christiane; Malberg, Sara; Römer-Oberdörfer, Angela; Staeheli, Peter; Rubbenstroth, Dennis

    2017-01-23

    Avian bornaviruses are causative agents of proventricular dilatation disease (PDD), a chronic neurologic and often fatal disorder of psittacines including endangered species. To date no causative therapy or immunoprophylaxis is available. Our previous work has shown that viral vector vaccines can delay the course of homologous bornavirus challenge infections but failed to protect against PDD when persistent infection was not prevented. The goal of this study was to refine our avian bornavirus vaccination and infection model to better represent natural bornavirus infections in order to achieve full protection against a heterologous challenge infection. We observed that parrot bornavirus 2 (PaBV-2) readily infected cockatiels (Nymphicus hollandicus) by combined intramuscular and subcutaneous injection with as little as 10(2.7)foci-forming units (ffu) per bird, whereas a 500-fold higher dose of the same virus administered via peroral and oculonasal route did not result in persistent infection. These results indicated that experimental bornavirus challenge infections with this virus should be performed via the parenteral route. Prime-boost vaccination of cockatiels with Newcastle disease virus (NDV) and modified vaccinia virus Ankara (MVA) vectors expressing the nucleoprotein and phosphoprotein genes of PaBV-4 substantially blocked bornavirus replication following parenteral challenge infection with 10(3.5)ffu of heterologous PaBV-2. Only two out of six vaccinated birds had very low viral levels detectable in a few organs. As a consequence, only one vaccinated bird developed mild PDD-associated microscopic lesions, while mock-vaccinated controls were not protected against PaBV-2 infection and inflammation. Our results demonstrate that NDV and MVA vector vaccines can protect against invasive heterologous bornavirus challenge infections and subsequent PDD. These vector vaccines represent a promising tool to combat avian bornaviruses in psittacine populations. Copyright

  3. Innate Immune Responses in Viral Hepatitis: the role of Kupffer cells and liver-derived monocytes in shaping intrahepatic immunity in mice using the LCMV infection model

    NARCIS (Netherlands)

    D. Movita (Dowty)

    2014-01-01

    markdownabstract__Abstract__ This study was performed to elucidate the immunological role of the liver in viral hepatitis. The immune functions of the liver are shaped by the intrahepatic cells present during steady state condition, as well as the recruited immune cells during liver

  4. Innate Immune Responses in Viral Hepatitis: the role of Kupffer cells and liver-derived monocytes in shaping intrahepatic immunity in mice using the LCMV infection model

    NARCIS (Netherlands)

    D. Movita (Dowty)

    2014-01-01

    markdownabstract__Abstract__ This study was performed to elucidate the immunological role of the liver in viral hepatitis. The immune functions of the liver are shaped by the intrahepatic cells present during steady state condition, as well as the recruited immune cells during liver inflammation.

  5. Viral respiratory infections among Hajj pilgrims in 2013

    Institute of Scientific and Technical Information of China (English)

    Osamah; Barasheed; Harunor; Rashid; Mohammad; Alfelali; Mohamed; Tashani; Mohammad; Azeem; Hamid; Bokhary; Nadeen; Kalantan; Jamil; Samkari; Leon; Heron; Jen; Kok; Janette; Taylor; Haitham; El; Bashir; Ziad; A.Memish; Elizabeth; Haworth; Edward; C.Holmes; Dominic; E; Dwyer; Atif; Asghar; Robert; Booy

    2014-01-01

    Middle East respiratory syndrome coronavirus(MERS-Co V) has emerged in the Arabian Gulf region, with its epicentre in Saudi Arabia, the host of the ‘Hajj’ which is the world’s the largest mass gathering. Transmission of MERS-Co V at such an event could lead to its rapid worldwide dissemination. Therefore, we studied the frequency of viruses causing influenza-like illnesses(ILI) among participants in a randomised controlled trial at the Hajj 2013. We recruited 1038 pilgrims from Saudi Arabia, Australia and Qatar during the first day of Hajj and followed them closely for four days. A nasal swab was collected from each pilgrim who developed ILI. Respiratory viruses were detected using multiplex RT-PCR. ILI occurred in 112/1038(11%) pilgrims. Their mean age was 35 years, 49(44%) were male and 35(31%) had received the influenza vaccine pre-Hajj. Forty two(38%) pilgrims had laboratory-confirmed viral infections; 28(25%) rhinovirus, 5(4%) influenza A, 2(2%) adenovirus, 2(2%) human coronavirus OC43/229 E, 2(2%) parainfluenza virus 3, 1(1%) parainfluenza virus 1, and 2(2%) dual infections. No MERS-Co V was detected in any sample. Rhinovirus was the commonest cause of ILI among Hajj pilgrims in 2013. Infection control and appropriate vaccination are necessary to prevent transmission of respiratory viruses at Hajj and other mass gatherings.

  6. Role of viral replication in extrahepatic syndromes related to hepatitis B virus infection.

    Science.gov (United States)

    Mason, A

    2006-03-01

    Approximately 20% of patients with hepatitis B virus (HBV) infection may experience extrahepatic disease. These manifestations include a viral prodrome with a serum sickness-like syndrome, polyarteritis nodosa, glomerulonephritis, as well as various neurological and dermatologic diseases amongst other manifestations. The viral pathogenesis is not well understood and has been difficult to study due to the lack of an animal model of HBV-related extrahepatic disease. Deposition of immune complexes and activation of the complement cascade has been most widely studied. However, circulating immune complexes are physiologic and occur more frequently than extrahepatic disease. Also, HBV-related extrahepatic syndromes occur in the absence of immune complex formation. Several studies support the notion that HBV replication in extrahepatic tissues may also precipitate disease but extrahepatic replication has commonly been observed without any apparent cytopathic or immune related tissue damage. It is clear that suppression of viral replication with antiviral therapy or spontaneous viral clearance positively correlates with resolution of extrahepatic disease. The use of continuous immunosuppressive therapy has largely been abandoned with the advent of robust antiviral strategies to manage disease. These data support the notion that a combination of factors including inadequate clearance immune complexes and viral replication in extrahepatic tissues play an important role in the pathogenesis. This conceptual framework is potentially significant as it emphasizes the importance of antiviral treatment in the management of extrahepatic disease.

  7. Interplay between viral infections and genetic alterations in liver cancer

    Directory of Open Access Journals (Sweden)

    Pierre Hainaut

    2007-02-01

    Full Text Available

    With over 500 000 annual deaths, Hepatocellular carcinoma (HCC is the fifth most common cancer worldwide and a leading cause of death in developing countries where about 80% of the cases arise. Risk factors include chronic hepatitis infections (hepatitis B, (HBV and hepatitis C (HCV viruses, alcohol, dietary contaminants such as falatoxins The incidence shows important geographic variations, accor In southern Asia, HCC development is mainly related to the endemic Hepatitis B Virus (HBV infection, cases with hot spot mutation in codon 249 (249ser of TP53 tumor suppressor gene were also described and associated to a low-intermediate exposure rate to Aflatoxin B1 (AFB1. Presence of Hepatitis C Virus (HCV infection was also detected in 12 - 17% of HCC cases. Despite the increasing number of studies identifying viral/host interactions in viro-induced HCC or describing potential pathways for hepatocarcinogenesis, precise mechanism has not been identified so far. HBV was demonstrated to enhance hepatocarcinogenesis by different manners; HBV chronic infection is associated to active hepatitis (CAH and cirrhosis which are hepatic complications considered as early stage for HCC development. These complications mobilise the host immune response, the resulting inflammation initiates and selects the first genetic alteration at the origin of loss of cell control. Moreover, HBV can also promote carcinogenesis through genetic instability generated by its common integration in host DNA. HBV proteins, as HBx, was proven to interact with a variety of targets in the host cell including protein or host transcription factor such as, in particular, the p53 protein or the transcription factor E4F, which is implicated in growth, differenciation and senescence. Specific HBV mutations or distinct HBV genotypes are associated to higher risks factors for HCC or hepatic complications leading

  8. Platelets and infection — an emerging role of platelets in viral infection

    Directory of Open Access Journals (Sweden)

    Alice eAssinger

    2014-12-01

    Full Text Available Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia and several platelet function disorders increase the risk of bleeding. Over the last years more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients.Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favours platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen-antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies.All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count, but also shapes immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation and platelet-mediated modulations of innate and adaptive immune responses.

  9. Platelets and infection - an emerging role of platelets in viral infection.

    Science.gov (United States)

    Assinger, Alice

    2014-01-01

    Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis) are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia) and several platelet function disorders increase the risk of bleeding. Over the last years, more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients. Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favors platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen-antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies. All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count but also shape immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation, and platelet-mediated modulations of innate and adaptive immune responses.

  10. Viral and atypical bacterial infections in the outpatient pediatric cystic fibrosis clinic

    DEFF Research Database (Denmark)

    Olesen, Hanne Vebert; Nielsen, Lars P; Schiotz, Peter Oluf

    2006-01-01

    for 12 months at regular clinic visits. Routine sputum/laryngeal aspirations were tested with PCR for 7 respiratory viruses. Antibodies against C. pneumoniae, M. pneumoniae and B. pertussis were measured every 3-4 months. FEV-1, FEF(25-75) and specific airway resistance, "viral" symptoms and bacterial.......039). Viral and atypical bacterial infections caused no change in type and frequency of bacterial culture. Positive predictive value of "viral symptoms" was low (0.64%). Eight patients received "unnecessary" antibiotics because of viral symptoms. CONCLUSIONS: Some viral infections and atypical bacterial......BACKGROUND: Respiratory viral and atypical bacterial infections are associated with pulmonary exacerbations and hospitalisations in cystic fibrosis patients. We wanted to study the impact of such infections on children attending the outpatient clinic. METHODS: Seventy-five children were followed...

  11. The association between invasive group A streptococcal diseases and viral respiratory tract infections

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    Andrea L Herrera

    2016-03-01

    Full Text Available Viral infections of the upper respiratory tract are associated with a variety of invasive diseases caused by Streptococcus pyogenes, the group A streptococcus, including pneumonia, necrotizing fasciitis, toxic shock syndrome, and bacteremia. While these polymicrobial infections, or superinfections, are complex, progress has been made in understanding the molecular basis of disease. Areas of investigation have included the characterization of virus-induced changes in innate immunity, differences in bacterial adherence and internalization following viral infection, and the efficacy of vaccines in mitigating the morbidity and mortality of superinfections. Here, we briefly summarize viral-S. pyogenes superinfections with an emphasis on those affiliated with influenza viruses.

  12. Pseudo-nitzschia Challenged with Co-occurring Viral Communities Display Diverse Infection Phenotypes.

    Science.gov (United States)

    Carlson, Michael C G; McCary, Nicolette D; Leach, Terence S; Rocap, Gabrielle

    2016-01-01

    Viruses are catalysts of biogeochemical cycling, architects of microbial community structure, and terminators of phytoplankton blooms. Viral lysis of diatoms, a key group of eukaryotic phytoplankton, has the potential to impact carbon export and marine food webs. However, the impact of viruses on diatom abundance and community composition is unknown. Diatom-virus dynamics were explored by sampling every month at two coastal and estuarine locations in Washington state, USA resulting in 41 new isolates of the pennate diatom Pseudo-nitzschia and 20 environmental virus samples. We conducted a total of 820 pair-wise crosses of the Pseudo-nitzschia isolates and viral communities. Viral communities infected Pseudo-nitzschia isolates in 8% of the crosses overall and 16% of crosses when the host and viral communities were isolated from the same sample. Isolates ranged in their permissivity to infection with some isolates not infected by any viral samples and others infected by up to 10 viral communities. Isolates that were infected by the most viral communities also had the highest maximum observed viral titers (as high as 16000 infectious units ml(-1)). Titers of the viral communities were host dependent, as titers for one viral sample on eight different hosts spanned four orders of magnitude. Sequencing of the Pseudo-nitzschia Internal Transcribed Spacer 1 (ITS1) of the revealed multiple subgroups of hosts with 100% ITS1 identities that were infected by different viral communities. Indeed, we repeatedly isolated groups of isolates with identical ITS1 sequences from the same water sample that displayed different viral infection phenotypes. The interactions between Pseudo-nitzschia and the viral communities highlight the diversity of diatoms and emphasize the complexity and variability of diatom-virus dynamics in the ocean.

  13. Pseudo-nitzschia challenged with co-occurring viral communities display diverse infection phenotypes

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    Michael Curtis Grier Carlson

    2016-04-01

    Full Text Available Viruses are catalysts of biogeochemical cycling, architects of microbial community structure, and terminators of phytoplankton blooms. Viral lysis of diatoms, a key group of eukaryotic phytoplankton, has the potential to impact carbon export and marine food webs. However, the impact of viruses on diatom abundance and community composition is unknown. Diatom-virus dynamics were explored by sampling every month at 2 coastal and estuarine locations in Washington state, USA resulting in 41 new isolates of the pennate diatom Pseudo-nitzschia and 20 environmental virus samples. We conducted a total of 820 pair-wise crosses of the Pseudo-nitzschia isolates and viral communities. Viral communities infected Pseudo-nitzschia isolates in 8% of the crosses overall and 16% of crosses when the host and viral communities were isolated from the same sample. Isolates ranged in their permissivity to infection with some isolates not infected by any viral samples and others infected by up to 10 viral communities. Isolates that were infected by the most viral communities also had the highest maximum observed viral titers (as high as 16000 infectious units ml-1. Titers of the viral communities were host dependent, as titers for one viral sample on 8 different hosts spanned 4 orders of magnitude. Sequencing of the Pseudo-nitzschia Internal Transcribed Spacer 1 (ITS1 of the revealed multiple subgroups of hosts with 100% ITS1 identity that were infected by different viral communities. Indeed, we repeatedly isolated groups of isolates with identical ITS1 sequences from the same water sample that displayed different viral infection phenotypes. The interactions between Pseudo-nitzschia and the viral communities highlight the diversity of diatoms and emphasize the complexity and variability of diatom-virus dynamics in the ocean.

  14. Protective Effect of Surfactant Protein D in Pulmonary Vaccinia Virus Infection: Implication of A27 Viral Protein

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    Julien Perino

    2013-03-01

    Full Text Available Vaccinia virus (VACV was used as a surrogate of variola virus (VARV (genus Orthopoxvirus, the causative agent of smallpox, to study Orthopoxvirus infection. VARV is principally transmitted between humans by aerosol droplets. Once inhaled, VARV first infects the respiratory tract where it could encounter surfactant components, such as soluble pattern recognition receptors. Surfactant protein D (SP-D, constitutively present in the lining fluids of the respiratory tract, plays important roles in innate host defense against virus infection. We investigated the role of SP-D in VACV infection and studied the A27 viral protein involvement in the interaction with SP-D. Interaction between SP-D and VACV caused viral inhibition in a lung cell model. Interaction of SP-D with VACV was mediated by the A27 viral protein. Binding required Ca2+ and interactions were blocked in the presence of excess of SP-D saccharide ligands. A27, which lacks glycosylation, directly interacted with SP-D. The interaction between SP-D and the viral particle was also observed using electron microscopy. Infection of mice lacking SP-D (SP-D-/- resulted in increased mortality compared to SP-D+/+ mice. Altogether, our data show that SP-D participates in host defense against the vaccinia virus infection and that the interaction occurs with the viral surface protein A27.

  15. Prophylaxis and therapy of viral infections in pediatric patients treated for malignancy

    OpenAIRE

    Licciardello, Maria; Pegoraro, Anna; Cesaro, Simone

    2011-01-01

    Infections are still an important cause of mortality and morbidity in pediatric cancer patients. Most of the febrile episodes in immunocompromised patients are classified as a fever of unknown origin (FUO) while bacteria are the more frequent causes of documented infections. Viral infections are also feared during chemotherapy but less data are available on their incidence and morbidity. We reviewed the literature on incidence, morbidity, and mortality of viral infections in children undergoi...

  16. [Detection of viral infection pathogens in medicinal plants grown in Ukraine].

    Science.gov (United States)

    Mishchenko, L T; Korenieva, A A; Molchanets', O V; Boĭko, A L

    2009-01-01

    Monitoring of viral infection on medicinal plant plantations is carried out. Panax ginseng C.A. Meyer, Valeriana officinalis L., Plantago major L. with symptoms of viral infection were revealed. Viral nature of symptoms was proved with biotesting method. Morphology and sizes of virus particles, detected in Panax ginseng method. Morphology and sizes of virus particles, detected in Panax ginseng C.A. Meyer, Valeriana officinalis L., Plantago major L., were determined with electron microscopy method. The paper is presented in Ukrainian.

  17. Alzheimer's disease gene signature says: beware of brain viral infections

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    Ianni Manuela

    2010-12-01

    Full Text Available Abstract Background Recent findings from a genome wide association investigation in a large cohort of patients with Alzheimer's disease (AD and non demented controls (CTR showed that a limited set of genes was in a strong association (p > l0-5 with the disease. Presentation of the hypothesis In this report we suggest that the polymorphism association in 8 of these genes is consistent with a non conventional interpretation of AD etiology. Nectin-2 (NC-2, apolipoprotein E (APOE, glycoprotein carcinoembryonic antigen related cell adhesion molecule- 16 (CEACAM-16, B-cell lymphoma-3 (Bcl-3, translocase of outer mitochondrial membrane 40 homolog (T0MM-40, complement receptor-1 (CR-l, APOJ or clusterin and C-type lectin domain A family-16 member (CLEC-16A result in a genetic signature that might affect individual brain susceptibility to infection by herpes virus family during aging, leading to neuronal loss, inflammation and amyloid deposition. Implications of the hypothesis We hypothesized that such genetic trait may predispose to AD via complex and diverse mechanisms each contributing to an increase of individual susceptibility to brain viral infections

  18. Papanicolaou smears induce partial immunity against sexually transmitted viral infections.

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    Shapiro, Samuel; Hoffman, Margaret; Constant, Deborah; Rosenberg, Lynn; Carrara, Henri; Allan, Bruce Rider; Marais, Dianne Jean; Passmore, Jo-Ann Shelley; Williamson, Anna-Lise

    2007-11-01

    In a case-control study of hormonal contraceptives and invasive cervical cancer, an unexpected finding was a substantial decline in the prevalence of high-risk human papillomavirus (HPV) infection according to the lifetime number of Pap smears received. Here we assess the risk of 3 sexually transmitted viral infections -- herpes simplex virus 2 (HSV2), HPV, and human immunodeficiency virus (HIV) 1 and 2 -- in relation to the lifetime receipt of Pap smears. Stored sera taken from 1540 controls were tested for HSV2 and HIV; cervical scrapings were tested for HPV. Confounder-adjusted odds ratios for the lifetime receipt of Pap smears were estimated, relative to never having had a Papanicolau test. For ever-receipt of a Papanicolau test, the odds ratios for HSV2 and HPV were 0.7 (95% confidence interval = 0.5-0.9) and 0.5 (0.3-0.7), respectively, and there were dose-response trends according to the lifetime number of Pap smears received (test for trend P = 0.02 and 0.04, respectively). For HSV2 the odds ratios according to last receipt declined from 0.8 for 10 or more years previously to 0.4 for <1 year previously (trend P = 0.002). For HPV the ORs were 0.4 (0.3-0.7) for last receipt 5-9 years previously and 0.5 (0.4-0.8) for less than 5 years previously; for HIV the odds ratio for last receipt less than 5 years previously was 0.4 (0.3-0.9). For HSV2 and HIV the crude odds ratio estimates were systematically lower than the adjusted estimates, and residual confounding cannot be ruled out. In particular, the true number of sexual partners may have been under-reported, and there was no information on the sexual activity of the male partners, or on other health behaviors of the women or their partners. We hypothesize that Pap smears may provoke a short-term immune response against sexually transmitted viral infections.

  19. EV71 infection correlates with viral IgG preexisting at pharyngolaryngeal mucosa in children

    Institute of Scientific and Technical Information of China (English)

    Jingchang; Xue; Yaoming; Li; Xiaoyi; Xu; Jie; Yu; Hu; Yan; Huimin; Yan

    2015-01-01

    Enterovirus 71(EV71) infection causes severe central nervous system damage, particularly for children under the age of 5 years old, which remains a major public health burden worldwide. Clinical data released that children may be repeatedly infected by different members in enterovirus and get even worsen. Mucosa, especially epithelium of alimentary canal, was considered the primary site of EV71 infection. It has been elusive whether the preexsiting viral antibody in mucosa plays a role in EV71 infection. To answer this question, we respectively measured viral antibody response and EV71 RNA copy number of one hundred throat swab specimens from clinically confirmed EV71-infected children. The results released that low-level of mucosal Ig G antibody against EV71 broadly existed in young population. More importantly, it further elucidated that the children with mucosal preexsiting EV71 Ig G were prone to be infected, which suggested a former viral Ig G mediated enhancement of viral infection in vivo.

  20. High Programmed Death-1 levels on HCV specific T cells during acute infection are associated with viral persistence and require preservation of cognate antigen during chronic infection1

    Science.gov (United States)

    Rutebemberwa, Alleluiah; Ray, Stuart C.; Astemborski, Jacquie; Levine, Jordana; Liu, Lin; Dowd, Kimberly A.; Clute, Shalyn; Wang, Changyu; Korman, Alan; Sette, Alessandro; Sidney, John; Pardoll, Drew M.; Cox, Andrea L.

    2009-01-01

    HCV is an important human pathogen that represents a model for chronic infection since the majority of infected individuals fail to clear the infection despite generation of virus-specific T cell responses during the period of acute infection. While viral sequence evolution at targeted MHC class I restricted epitopes represents one mechanism for immune escape in HCV, many targeted epitopes remain intact under circumstances of viral persistence. In order to explore alternative mechanisms of HCV immune evasion, we analyzed patterns of expression of a major inhibitory receptor on T cells, programmed death-1 (PD-1), from the time of initial infection and correlated these with HCV RNA levels, outcome of infection, and sequence escape within the targeted epitope. We show that the level of PD-1 expression in early HCV infection is significantly higher on HCV-specific T cells from those who progress to chronic HCV infection compared to those who clear infection. This correlation is independent of HCV RNA levels, compatible with the notion that high PD-1 expression on HCV-specific CD8 T cells during acute infection inhibits viral clearance. Viral escape during persistent infection is associated with reduction in PD-1 levels on the surface of HCV specific T cells, supporting the necessity of ongoing antigenic stimulation of T cells for maintenance of PD-1 expression. These results support the idea that PD-1 expression on T cells specific for nonescaped epitopes contributes to viral persistence and suggest that PD-1 blockade may alter the outcome of HCV infection. PMID:19050238

  1. Modeling the three stages in HIV infection.

    Science.gov (United States)

    Hernandez-Vargas, Esteban A; Middleton, Richard H

    2013-03-07

    A typical HIV infection response consists of three stages: an initial acute infection, a long asymptomatic period and a final increase in viral load with simultaneous collapse in healthy CD4+T cell counts. The majority of existing mathematical models give a good representation of either the first two stages or the last stage of the infection. Using macrophages as a long-term active reservoir, a deterministic model is proposed to explain the three stages of the infection including the progression to AIDS. Simulation results illustrate how chronic infected macrophages can explain the progression to AIDS provoking viral explosion. Further simulation studies suggest that the proposed model retains its key properties even under moderately large parameter variations. This model provides important insights on how macrophages might play a crucial role in the long term behavior of HIV infection. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  2. Experimental infection with non-cytopathic bovine viral diarrhea virus 1 in mice induces inflammatory cell infiltration in the spleen.

    Science.gov (United States)

    Han, Yu-Jung; Kwon, Young-Je; Lee, Kyung-Hyun; Choi, Eun-Jin; Choi, Kyoung-Seong

    2016-09-01

    Previously, our study showed that oral inoculation of mice with cytopathic (cp) bovine viral diarrhea virus (BVDV) led to lymphocyte depletion and increased numbers of megakaryocytes in the spleen as well as thrombocytopenia and lymphopenia. In the present study, to investigate the possible differences in the detection of viral antigen, histopathological lesions, and hematologic changes between non-cytopathic (ncp) BVDV1 and cp BVDV1, mice were orally administered low and high doses of ncp BVDV1 and were necropsied at days 0, 2, 5, and 9 postinfection (pi). None of the ncp BVDV1-infected mice exhibited clinical signs of illness, unlike those infected with cp BVDV1. Statistically significant thrombocytopenia was observed during ncp BVDV1 infection, and lymphopenia was found only in mice infected with a high dose at day 9 pi. Interestingly, ncp BVDV1 infection increased the numbers of basophils, eosinophils, neutrophils, and monocytes in some infected mice. Viral antigen was detected in the lymphocytes of the spleen, mesenteric lymph nodes, Peyer's patches, and bone marrow by immunohistochemistry. Lymphoid depletion was evident in the mesenteric lymph nodes of mice infected with a high dose and also found in the Peyer's patches of some infected mice. Infiltration of inflammatory cells, including neutrophils and monocytes, and an increased number of megakaryocytes were seen in the spleen. These results suggest that the distribution of viral antigens is not associated with the presence of histopathological lesions. Inflammatory cell infiltration was observed in the spleens as a result of viral replication and may be attributable to the host reaction to ncp BVDV1 infection. Together, these findings support the possibility that mice can be used as an animal model for BVDV infection.

  3. The control of viral infection by tripartite motif proteins and cyclophilin A

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    Towers Greg J

    2007-06-01

    Full Text Available Abstract The control of retroviral infection by antiviral factors referred to as restriction factors has become an exciting area in infectious disease research. TRIM5α has emerged as an important restriction factor impacting on retroviral replication including HIV-1 replication in primates. TRIM5α has a tripartite motif comprising RING, B-Box and coiled coil domains. The antiviral α splice variant additionally encodes a B30.2 domain which is recruited to incoming viral cores and determines antiviral specificity. TRIM5 is ubiquitinylated and rapidly turned over by the proteasome in a RING dependent way. Protecting restricted virus from degradation, by inhibiting the proteasome, rescues DNA synthesis, but not infectivity, indicating that restriction of infectivity by TRIM5α does not depend on the proteasome but the early block to DNA synthesis is likely to be mediated by rapid degradation of the restricted cores. The peptidyl prolyl isomerase enzyme cyclophilin A isomerises a peptide bond on the surface of the HIV-1 capsid and impacts on sensitivity to restriction by TRIM5α from Old World monkeys. This suggests that TRIM5α from Old World monkeys might have a preference for a particular capsid isomer and suggests a role for cyclophilin A in innate immunity in general. Whether there are more human antiviral TRIMs remains uncertain although the evidence for TRIM19's (PML antiviral properties continues to grow. A TRIM5-like molecule with broad antiviral activity in cattle suggests that TRIM mediated innate immunity might be common in mammals. Certainly the continued study of restriction of viral infectivity by antiviral host factors will remain of interest to a broad audience and impact on a variety of areas including development of animal models for infection, development of viral vectors for gene therapy and the search for novel antiviral drug targets.

  4. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco.

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    Moupali Das

    Full Text Available BACKGROUND: At the individual level, higher HIV viral load predicts sexual transmission risk. We evaluated San Francisco's community viral load (CVL as a population level marker of HIV transmission risk. We hypothesized that the decrease in CVL in San Francisco from 2004-2008, corresponding with increased rates of HIV testing, antiretroviral therapy (ART coverage and effectiveness, and population-level virologic suppression, would be associated with a reduction in new HIV infections. METHODOLOGY/PRINCIPAL FINDINGS: We used San Francisco's HIV/AIDS surveillance system to examine the trends in CVL. Mean CVL was calculated as the mean of the most recent viral load of all reported HIV-positive individuals in a particular community. Total CVL was defined as the sum of the most recent viral loads of all HIV-positive individuals in a particular community. We used Poisson models with robust standard errors to assess the relationships between the mean and total CVL and the primary outcome: annual numbers of newly diagnosed HIV cases. Both mean and total CVL decreased from 2004-2008 and were accompanied by decreases in new HIV diagnoses from 798 (2004 to 434 (2008. The mean (p = 0.003 and total CVL (p = 0.002 were significantly associated with new HIV cases from 2004-2008. CONCLUSIONS/SIGNIFICANCE: Reductions in CVL are associated with decreased HIV infections. Results suggest that wide-scale ART could reduce HIV transmission at the population level. Because CVL is temporally upstream of new HIV infections, jurisdictions should consider adding CVL to routine HIV surveillance to track the epidemic, allocate resources, and to evaluate the effectiveness of HIV prevention and treatment efforts.

  5. Clinical guidelines for the management of acute viral infections in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Ramos-Casals, M; Cuadrado, M J; Alba, P; Sanna, G; Brito-Zerón, P; Bertolaccini, L; Babini, A; Moreno, A; D'Cruz, D; Khamashta, M A

    2009-12-01

    In recent decades, many research groups have focused on the role of viral infections in the etiopathogenesis of systemic lupus erythematosus (SLE), the so-called "viral hypothesis". The main candidates are herpes viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), which have a high seroprevalence in the general population. However, a viral causal agent of SLE has not yet been discovered, although many interesting clinical findings on the complex interactions between viruses and SLE have been made. This review analyzes 88 cases of acute viral infections in adult patients with SLE and identifies situations in which viral infections influenced the diagnosis, prognosis or treatment of SLE. We also propose clinical guidelines for the management of these infections in patients with SLE.

  6. MicroRNAs in the host response to viral infections of veterinary importance

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    Mohamed Samir Ahmed

    2016-10-01

    Full Text Available The discovery of small regulatory non-coding RNAs has been an exciting advance in the field of genomics. MicroRNAs (miRNAs are endogenous RNA molecules, approximately 22 nucleotides in length that regulate gene expression, mostly at the post-transcriptional level. MiRNA profiling technologies have made it possible to identify and quantify novel miRNAs and to study their regulation and potential roles in disease pathogenesis. Although miRNAs have been extensively investigated in viral infections of humans, their implications in viral diseases affecting animals of veterinary importance are much less understood. The number of annotated miRNAs in different animal species is growing continuously, and novel roles in regulating host-pathogen interactions are being discovered, for instance miRNA-mediated augmentation of viral transcription and replication. In this review, we present an overview of synthesis and function of miRNAs and an update on the current state of research on host-encoded miRNAs in the genesis of viral infectious diseases in their natural animal host as well as in selected in vivo and in vitro laboratory models.

  7. Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication.

    Science.gov (United States)

    Dutartre, Hélène; Clavière, Mathieu; Journo, Chloé; Mahieux, Renaud

    2016-09-01

    Human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) are complex retroviruses mainly infecting CD4(+) T lymphocytes. In addition, antigen-presenting cells such as dendritic cells (DCs) are targeted in vivo by both viruses, although to a lesser extent. Interaction of HIV-1 with DCs plays a key role in viral dissemination from the mucosa to CD4(+) T lymphocytes present in lymphoid organs. While similar mechanisms may occur for HTLV-1 as well, most HTLV-1 data were obtained from T-cell studies, and little is known regarding the trafficking of this virus in DCs. We first compared the efficiency of cell-free versus cell-associated viral sources of both retroviruses at infecting DCs. We showed that both HIV-1 and HTLV-1 cell-free particles are poorly efficient at productively infecting DCs, except when DC-SIGN has been engaged. Furthermore, while SAMHD-1 accounts for restriction of cell-free HIV-1 infection, it is not involved in HTLV-1 restriction. In addition, cell-free viruses lead mainly to a nonproductive DC infection, leading to trans-infection of T-cells, a process important for HIV-1 spread but not for that of HTLV-1. Finally, we show that T-DC cell-to-cell transfer implies viral trafficking in vesicles that may both increase productive infection of DCs ("cis-infection") and allow viral escape from immune surveillance. Altogether, these observations allowed us to draw a model of HTLV-1 and HIV-1 trafficking in DCs.

  8. TREM-2 promotes macrophage survival and lung disease after respiratory viral infection

    Science.gov (United States)

    Wu, Kangyun; Byers, Derek E.; Jin, Xiaohua; Agapov, Eugene; Alexander-Brett, Jennifer; Patel, Anand C.; Cella, Marina; Gilfilan, Susan; Colonna, Marco; Kober, Daniel L.; Brett, Tom J.

    2015-01-01

    Viral infections and type 2 immune responses are thought to be critical for the development of chronic respiratory disease, but the link between these events needs to be better defined. Here, we study a mouse model in which infection with a mouse parainfluenza virus known as Sendai virus (SeV) leads to long-term activation of innate immune cells that drive IL-13–dependent lung disease. We find that chronic postviral disease (signified by formation of excess airway mucus and accumulation of M2-differentiating lung macrophages) requires macrophage expression of triggering receptor expressed on myeloid cells-2 (TREM-2). Analysis of mechanism shows that viral replication increases lung macrophage levels of intracellular and cell surface TREM-2, and this action prevents macrophage apoptosis that would otherwise occur during the acute illness (5–12 d after inoculation). However, the largest increases in TREM-2 levels are found as the soluble form (sTREM-2) long after clearance of infection (49 d after inoculation). At this time, IL-13 and the adapter protein DAP12 promote TREM-2 cleavage to sTREM-2 that is unexpectedly active in preventing macrophage apoptosis. The results thereby define an unprecedented mechanism for a feed-forward expansion of lung macrophages (with IL-13 production and consequent M2 differentiation) that further explains how acute infection leads to chronic inflammatory disease. PMID:25897174

  9. Viral infection in community-acquired pneumonia: a systematic review and meta-analysis

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    Michael Burk

    2016-06-01

    Full Text Available The advent of PCR has improved the identification of viruses in patients with community-acquired pneumonia (CAP. Several studies have used PCR to establish the importance of viruses in the aetiology of CAP. We performed a systematic review and meta-analysis of the studies that reported the proportion of viral infection detected via PCR in patients with CAP. We excluded studies with paediatric populations. The primary outcome was the proportion of patients with viral infection. The secondary outcome was short-term mortality. Our review included 31 studies. Most obtained PCR via nasopharyngeal or oropharyngeal swab. The pooled proportion of patients with viral infection was 24.5% (95% CI 21.5–27.5%. In studies that obtained lower respiratory samples in >50% of patients, the proportion was 44.2% (95% CI 35.1–53.3%. The odds of death were higher in patients with dual bacterial and viral infection (OR 2.1, 95% CI 1.32–3.31. Viral infection is present in a high proportion of patients with CAP. The true proportion of viral infection is probably underestimated because of negative test results from nasopharyngeal or oropharyngeal swab PCR. There is increased mortality in patients with dual bacterial and viral infection.

  10. Direct infection of dendritic cells during chronic viral infection suppresses antiviral T cell proliferation and induces IL-10 expression in CD4 T cells.

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    Carmen Baca Jones

    Full Text Available Elevated levels of systemic IL-10 have been associated with several chronic viral infections, including HCV, EBV, HCMV and LCMV. In the chronic LCMV infection model, both elevated IL-10 and enhanced infection of dendritic cells (DCs are important for viral persistence. This report highlights the relationship between enhanced viral tropism for DCs and the induction of IL-10 in CD4 T cells, which we identify as the most frequent IL-10-expressing cell type in chronic LCMV infection. Here we report that infected CD8αneg DCs express elevated IL-10, induce IL-10 expression in LCMV specific CD4 T cells, and suppress LCMV-specific T cell proliferation. DCs exposed in vivo to persistent LCMV retain the capacity to stimulate CD4 T cell proliferation but induce IL-10 production by both polyclonal and LCMV-specific CD4 T cells. Our study delineates the unique effects of direct infection versus viral exposure on DCs. Collectively these data point to enhanced infection of DCs as a key trigger of the IL-10 induction cascade resulting in maintenance of elevated IL-10 expression in CD4 T cells and inhibition of LCMV-specific CD4 and CD8 T cell proliferation.

  11. An HIV epidemic model based on viral load dynamics: value in assessing empirical trends in HIV virulence and community viral load.

    Science.gov (United States)

    Herbeck, Joshua T; Mittler, John E; Gottlieb, Geoffrey S; Mullins, James I

    2014-06-01

    Trends in HIV virulence have been monitored since the start of the AIDS pandemic, as studying HIV virulence informs our understanding of HIV epidemiology and pathogenesis. Here, we model changes in HIV virulence as a strictly evolutionary process, using set point viral load (SPVL) as a proxy, to make inferences about empirical SPVL trends from longitudinal HIV cohorts. We develop an agent-based epidemic model based on HIV viral load dynamics. The model contains functions for viral load and transmission, SPVL and disease progression, viral load trajectories in multiple stages of infection, and the heritability of SPVL across transmissions. We find that HIV virulence evolves to an intermediate level that balances infectiousness with longer infected lifespans, resulting in an optimal SPVL∼4.75 log10 viral RNA copies/mL. Adaptive viral evolution may explain observed HIV virulence trends: our model produces SPVL trends with magnitudes that are broadly similar to empirical trends. With regard to variation among studies in empirical SPVL trends, results from our model suggest that variation may be explained by the specific epidemic context, e.g. the mean SPVL of the founding lineage or the age of the epidemic; or improvements in HIV screening and diagnosis that results in sampling biases. We also use our model to examine trends in community viral load, a population-level measure of HIV viral load that is thought to reflect a population's overall transmission potential. We find that community viral load evolves in association with SPVL, in the absence of prevention programs such as antiretroviral therapy, and that the mean community viral load is not necessarily a strong predictor of HIV incidence.

  12. An HIV epidemic model based on viral load dynamics: value in assessing empirical trends in HIV virulence and community viral load.

    Directory of Open Access Journals (Sweden)

    Joshua T Herbeck

    2014-06-01

    Full Text Available Trends in HIV virulence have been monitored since the start of the AIDS pandemic, as studying HIV virulence informs our understanding of HIV epidemiology and pathogenesis. Here, we model changes in HIV virulence as a strictly evolutionary process, using set point viral load (SPVL as a proxy, to make inferences about empirical SPVL trends from longitudinal HIV cohorts. We develop an agent-based epidemic model based on HIV viral load dynamics. The model contains functions for viral load and transmission, SPVL and disease progression, viral load trajectories in multiple stages of infection, and the heritability of SPVL across transmissions. We find that HIV virulence evolves to an intermediate level that balances infectiousness with longer infected lifespans, resulting in an optimal SPVL∼4.75 log10 viral RNA copies/mL. Adaptive viral evolution may explain observed HIV virulence trends: our model produces SPVL trends with magnitudes that are broadly similar to empirical trends. With regard to variation among studies in empirical SPVL trends, results from our model suggest that variation may be explained by the specific epidemic context, e.g. the mean SPVL of the founding lineage or the age of the epidemic; or improvements in HIV screening and diagnosis that results in sampling biases. We also use our model to examine trends in community viral load, a population-level measure of HIV viral load that is thought to reflect a population's overall transmission potential. We find that community viral load evolves in association with SPVL, in the absence of prevention programs such as antiretroviral therapy, and that the mean community viral load is not necessarily a strong predictor of HIV incidence.

  13. Zebrafish: modeling for herpes simplex virus infections.

    Science.gov (United States)

    Antoine, Thessicar Evadney; Jones, Kevin S; Dale, Rodney M; Shukla, Deepak; Tiwari, Vaibhav

    2014-02-01

    For many years, zebrafish have been the prototypical model for studies in developmental biology. In recent years, zebrafish has emerged as a powerful model system to study infectious diseases, including viral infections. Experiments conducted with herpes simplex virus type-1 in adult zebrafish or in embryo models are encouraging as they establish proof of concept with viral-host tropism and possible screening of antiviral compounds. In addition, the presence of human homologs of viral entry receptors in zebrafish such as 3-O sulfated heparan sulfate, nectins, and tumor necrosis factor receptor superfamily member 14-like receptor bring strong rationale for virologists to test their in vivo significance in viral entry in a zebrafish model and compare the structure-function basis of virus zebrafish receptor interaction for viral entry. On the other end, a zebrafish model is already being used for studying inflammation and angiogenesis, with or without genetic manipulations, and therefore can be exploited to study viral infection-associated pathologies. The major advantage with zebrafish is low cost, easy breeding and maintenance, rapid lifecycle, and a transparent nature, which allows visualizing dissemination of fluorescently labeled virus infection in real time either at a localized region or the whole body. Further, the availability of multiple transgenic lines that express fluorescently tagged immune cells for in vivo imaging of virus infected animals is extremely attractive. In addition, a fully developed immune system and potential for receptor-specific knockouts further advocate the use of zebrafish as a new tool to study viral infections. In this review, we focus on expanding the potential of zebrafish model system in understanding human infectious diseases and future benefits.

  14. Synaptic transmission and the susceptibility of HIV infection to anti-viral drugs

    Science.gov (United States)

    Komarova, Natalia L.; Levy, David N.; Wodarz, Dominik

    2013-07-01

    Cell-to-cell viral transmission via virological synapses has been argued to reduce susceptibility of the virus population to anti-viral drugs through multiple infection of cells, contributing to low-level viral persistence during therapy. Using a mathematical framework, we examine the role of synaptic transmission in treatment susceptibility. A key factor is the relative probability of individual virions to infect a cell during free-virus and synaptic transmission, a currently unknown quantity. If this infection probability is higher for free-virus transmission, then treatment susceptibility is lowest if one virus is transferred per synapse, and multiple infection of cells increases susceptibility. In the opposite case, treatment susceptibility is minimized for an intermediate number of virions transferred per synapse. Hence, multiple infection via synapses does not simply lower treatment susceptibility. Without further experimental investigations, one cannot conclude that synaptic transmission provides an additional mechanism for the virus to persist at low levels during anti-viral therapy.

  15. Interleukin-1 mediates long-term hippocampal dentate granule cell loss following postnatal viral infection.

    Science.gov (United States)

    Orr, Anna G; Sharma, Anup; Binder, Nikolaus B; Miller, Andrew H; Pearce, Bradley D

    2010-05-01

    Viral infections of the developing CNS can cause long-term neuropathological sequela through undefined mechanisms. Proinflammatory cytokines such as IL-1beta have gained attention in mediating neurodegeneration in corticohippocampal structures due to a variety of insults in adults, though there is less information on the developing brain. Little is known concerning the spatial-temporal pattern of IL-1beta induction in the developing hippocampus following live virus infection, and there are few studies addressing the long-term consequences of this cytokine induction. We report that infection of rats with lymphocytic choriomeningitis virus on postnatal day 4 induces IL-1beta protein in select regions of the hippocampus on 6, 15, 21, and 45 days after infection. This infection resulted in a 71% reduction of dentate granule cell neurons by the time the rats reached mid-adulthood. We further investigated the causative role of IL-1 in this dentate granule cell loss by blocking IL-1 activity using an IL-1ra-expressing adenoviral vector administered at the time of infection. Blockade of IL-1 abrogated the infection-associated neuron loss in this vivo model. Considering that IL-1 can be triggered by multiple perinatal insults, our findings suggest that early therapy with anti-inflammatory agents that block IL-1 may be effective for reducing adulthood neuropathology.

  16. Regulation of T cell migration during viral infection: role of adhesion molecules and chemokines

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Nansen, Anneline; Madsen, Andreas Nygaard

    2003-01-01

    T cell mediated immunity and in particular CD8+ T cells are pivotal for the control of most viral infections. T cells exclusively exert their antiviral effect through close cellular interaction with relevant virus-infected target cells in vivo. It is therefore imperative that efficient mechanisms...... exist, which will rapidly direct newly generated effector T cells to sites of viral replication. In the present report we have reviewed our present knowledge concerning the molecular interactions, which are important in targeting of effector CD8+ T cells to sites of viral infection....

  17. p53 Activation following Rift Valley fever virus infection contributes to cell death and viral production.

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    Dana Austin

    Full Text Available Rift Valley fever virus (RVFV is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production.

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

    Science.gov (United States)

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

    2015-05-01

    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. 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. Our data demonstrate

  19. High numbers of IL-2-producing CD8+ T cells during viral infection: correlation with stable memory development

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2002-01-01

    that IL-2-producing cells appear slightly delayed compared with the majority of IFN-gamma producing cells, and the relative frequency of the IL-2-producing subset increases with transition into the memory phase. In contrast to acute immunizing infection, few IL-2-producing cells are generated during......Using infections with lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus in mice as model systems, we have investigated the ability of antigen-primed CD8+ T cells generated in the context of viral infections to produce IL-2. Our results indicate that acute immunizing infection...

  20. Immune and viral correlates of "secondary viral control" after treatment interruption in chronically HIV-1 infected patients.

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    Ellen Van Gulck

    Full Text Available Upon interruption of antiretroviral therapy, HIV-infected patients usually show viral load rebound to pre-treatment levels. Four patients, hereafter referred to as secondary controllers (SC, were identified who initiated therapy during chronic infection and, after stopping treatment, could control virus replication at undetectable levels for more than six months. In the present study we set out to unravel possible viral and immune parameters or mechanisms of this phenomenon by comparing secondary controllers with elite controllers and non-controllers, including patients under HAART. As candidate correlates of protection, virus growth kinetics, levels of intracellular viral markers, several aspects of HIV-specific CD4+ and CD8+ T cell function and HIV neutralizing antibodies were investigated. As expected all intracellular viral markers were lower in aviremic as compared to viremic subjects, but in addition both elite and secondary controllers had lower levels of viral unspliced RNA in PBMC as compared to patients on HAART. Ex vivo cultivation of the virus from CD4+ T cells of SC consistently failed in one patient and showed delayed kinetics in the three others. Formal in vitro replication studies of these three viruses showed low to absent growth in two cases and a virus with normal fitness in the third case. T cell responses toward HIV peptides, evaluated in IFN-γ ELISPOT, revealed no significant differences in breadth, magnitude or avidity between SC and all other patient groups. Neither was there a difference in polyfunctionality of CD4+ or CD8+ T cells, as evaluated with intracellular cytokine staining. However, secondary and elite controllers showed higher proliferative responses to Gag and Pol peptides. SC also showed the highest level of autologous neutralizing antibodies. These data suggest that higher T cell proliferative responses and lower replication kinetics might be instrumental in secondary viral control in the absence of

  1. Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA.

    Science.gov (United States)

    Lanford, Robert E; Feng, Zongdi; Chavez, Deborah; Guerra, Bernadette; Brasky, Kathleen M; Zhou, Yan; Yamane, Daisuke; Perelson, Alan S; Walker, Christopher M; Lemon, Stanley M

    2011-07-05

    Hepatitis A virus (HAV) is an hepatotropic human picornavirus that is associated only with acute infection. Its pathogenesis is not well understood because there are few studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by quantitative RT-PCR and examining critical aspects of the innate immune response including intrahepatic IFN-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), an hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I IFN-stimulated genes in the liver compared with chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal IFN-stimulated gene 15 and IFIT1 responses peaked 1-2 wk after HAV challenge and then subsided despite continuing high hepatic viral RNA. An acute inflammatory response at 3-4 wk correlated with the appearance of virus-specific antibodies and apoptosis and proliferation of hepatocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for significantly longer (35 to >48 wk) than HCV RNA in animals with acute resolving HCV infection (10-20 wk). Collectively, these findings indicate that HAV is far stealthier than HCV early in the course of acute resolving infection. HAV infections represent a distinctly different paradigm in virus-host interactions within the liver.

  2. Experimental infection of pregnant goats with bovine viral diarrhea virus (BVDV)1 or 2

    Science.gov (United States)

    Infections with bovine viral diarrhea virus (BVDV) of the genus pestivirus, family Flaviviridae, are not limited to cattle but occur in various artiodactyls. Persistently infected (PI) cattle are the main source of BVDV. Persistent infections also occur in heterologous hosts such as sheep and deer. ...

  3. Innate Immunity and the Inter-exposure Interval Determine the Dynamics of Secondary Influenza Virus Infection and Explain Observed Viral Hierarchies.

    Directory of Open Access Journals (Sweden)

    Pengxing Cao

    2015-08-01

    Full Text Available Influenza is an infectious disease that primarily attacks the respiratory system. Innate immunity provides both a very early defense to influenza virus invasion and an effective control of viral growth. Previous modelling studies of virus-innate immune response interactions have focused on infection with a single virus and, while improving our understanding of viral and immune dynamics, have been unable to effectively evaluate the relative feasibility of different hypothesised mechanisms of antiviral immunity. In recent experiments, we have applied consecutive exposures to different virus strains in a ferret model, and demonstrated that viruses differed in their ability to induce a state of temporary immunity or viral interference capable of modifying the infection kinetics of the subsequent exposure. These results imply that virus-induced early immune responses may be responsible for the observed viral hierarchy. Here we introduce and analyse a family of within-host models of re-infection viral kinetics which allow for different viruses to stimulate the innate immune response to different degrees. The proposed models differ in their hypothesised mechanisms of action of the non-specific innate immune response. We compare these alternative models in terms of their abilities to reproduce the re-exposure data. Our results show that 1 a model with viral control mediated solely by a virus-resistant state, as commonly considered in the literature, is not able to reproduce the observed viral hierarchy; 2 the synchronised and desynchronised behaviour of consecutive virus infections is highly dependent upon the interval between primary virus and challenge virus exposures and is consistent with virus-dependent stimulation of the innate immune response. Our study provides the first mechanistic explanation for the recently observed influenza viral hierarchies and demonstrates the importance of understanding the host response to multi-strain viral infections

  4. Viral persistence, liver disease and host response in Hepatitis C-like virus rat model

    DEFF Research Database (Denmark)

    Trivedi, Sheetal; Murthy, Satyapramod; Sharma, Himanshu

    2017-01-01

    The lack of a relevant, tractable, and immunocompetent animal model for hepatitis C virus (HCV) has severely impeded investigations of viral persistence, immunity and pathogenesis. In the absence of immunocompetent models with robust HCV infection, homolog hepaciviruses in their natural host coul......, immunity and pathogenesis. This article is protected by copyright. All rights reserved....

  5. Pathology and viral antigen distribution following experimental infection of sheep and goats with capripoxvirus.

    Science.gov (United States)

    Embury-Hyatt, C; Babiuk, S; Manning, L; Ganske, S; Bowden, T R; Boyle, D B; Copps, J

    2012-01-01

    Current understanding of capripoxvirus pathogenesis is limited since there have been no detailed studies examining cell tropism at well-defined intervals following infection. We undertook time-course studies in sheep and goats following inoculation of sheeppox or goatpox viruses in their respective homologous hosts, and examined tissues by light microscopy. A monoclonal antibody generated to a sheeppox virus core protein was used for immunohistochemical detection of viral antigen in tissue sections. Lesions and virus antigen were observed consistently in the skin, lung and lymph nodes. Antigen was detected at 6 and 8 days post inoculation for skin and lung, respectively, within cells which appeared to be of monocyte/macrophage lineage. In sheep skin capripoxvirus immunoreactivity was detected within previously unreported large multinucleated cells. In the lung, double immunolabelling detected the simultaneous expression of capripoxvirus antigen and cytokeratin indicating the presence of virus within pneumocytes. Lung double immunolabelling also detected the expression of capripoxvirus antigen in CD68(+) cells, confirming the presence of viral antigen within macrophages. Based on early detection of infected macrophages, dissemination of virus within the host and localization to tissues likely occurred through cells of the monocyte/macrophage lineage. Histological findings revealed similarities with both monkeypox and smallpox, thus capripoxvirus infection in sheep and goats may represent useful models with which to study strategies for poxvirus-specific virus vaccine concepts and therapeutics.

  6. Determining host metabolic limitations on viral replication via integrated modeling and experimental perturbation.

    Directory of Open Access Journals (Sweden)

    Elsa W Birch

    Full Text Available Viral replication relies on host metabolic machinery and precursors to produce large numbers of progeny - often very rapidly. A fundamental example is the infection of Escherichia coli by bacteriophage T7. The resource draw imposed by viral replication represents a significant and complex perturbation to the extensive and interconnected network of host metabolic pathways. To better understand this system, we have integrated a set of structured ordinary differential equations quantifying T7 replication and an E. coli flux balance analysis metabolic model. Further, we present here an integrated simulation algorithm enforcing mutual constraint by the models across the entire duration of phage replication. This method enables quantitative dynamic prediction of virion production given only specification of host nutritional environment, and predictions compare favorably to experimental measurements of phage replication in multiple environments. The level of detail of our computational predictions facilitates exploration of the dynamic changes in host metabolic fluxes that result from viral resource consumption, as well as analysis of the limiting processes dictating maximum viral progeny production. For example, although it is commonly assumed that viral infection dynamics are predominantly limited by the amount of protein synthesis machinery in the host, our results suggest that in many cases metabolic limitation is at least as strict. Taken together, these results emphasize the importance of considering viral infections in the context of host metabolism.

  7. VIRAL ETIOLOGY ACUTE INTESTINAL INFECTIONS MOLECULAR MONITORING IN CHILDREN’S HOSPITAL

    Directory of Open Access Journals (Sweden)

    A. V. Sergeeva

    2015-01-01

    Full Text Available On the territory of the Russian Federation in the overall structure of acute intestinal infections the proportion of viral diarrhea among children varies from 24 to 78% of cases depending on the season. The acute viral intestinal infections etiological confirmation is performed mainly among patients of infectious hospitals. The prevalence of viral acute intestinal infections in non-infectious hospitals, including infections associated with medical care, remains unclear. Currently estimation of viral component in the acute intestinal infections overall structure mainly consists in determination of rotavirus infection prevalence excluding other pathogens. As the part of viral etiology hospital infections epidemiological surveillance in non-infections children’s hospital the study of acute viral intestinal infections etiological structure and molecular genetics characterization of identified enteric viruses is conducted. The syndrome diagnosis of acute intestinal infections cases was introduced — an identification and evaluation of patients with signs of dysfunction of the gastrointestinal tract, that is not related to the underlying disease. A set of laboratory methods included identification of various intestinal pathogens DNA (RNA by PCR-RT method; genotyping of enteric viruses using sequencing; nucleotide sequence analysis of cDNA fragments using the BLAST software package for identification of closely related strains and an online service for automatic genotyping of noroviruses by Norovirus Genotyping Tool Version 1.0. Alignment of nucleotide sequences and phylogenetic analysis was performed using the software MEGA 5.0. The obtained sequence fragments of the genome was downloaded in GenBank international database. The use of molecular genetics research methods allowed to differentiate viral pathogens of acute intestinal infections and to establish the fact of nosocomial transmission. The proportion of viral etiology acute intestinal

  8. Viral etiology of acute respiratory infections (ari) in old adults from ageriatric care unit

    OpenAIRE

    Beltrán, Karent Julieth; Grupo de Enfermedades Infecciosas, Línea de investigación Microbiología Molecular y Aplicada de las enfermedades Infecciosas, Pontificia Universidad Javeriana, Bogotá-Colombia.; Segura, Juan Camilo; Pontificia Universidad Javeriana, Bogotá-Colombia; Bettin, Laura; Pontificia Universidad Javeriana, Bogotá-Colombia; Coriat, Jeanette; Programa de Medicina, Pontificia Universidad Javeriana, Bogotá-Colombia; Mercado, Marcela; Instituto Nacional de Salud, Bogotá-Colombia.; Hidalgo, Marylin; Grupo de Enfermedades Infecciosas, Departamento de Microbiología. Facultad de Ciencias. Pontificia Universidad Javeriana. Bogotá, D.C. Colombia.; Díez, Hugo; Grupo de Enfermedades Infecciosas, Pontificia Universidad Javeriana, Bogotá-Colombia.

    2015-01-01

    Objective: To determine viral etiology of acute respiratory infections in older-than-60 adults, living at 4 geriatric care units in Bogota.Methods: The study was performed in two phases: Phase 1: Descriptive prospective study to evaluate incidence of viral respiratory infection during 1 year in old adults. 71 patients, suffering respiratory diseases, were selected, and evaluated, including physical exploration, thorax X-ray, and collection of respiratory samples for analysis. In order to dete...

  9. Wolbachia Blocks Viral Genome Replication Early in Infection without a Transcriptional Response by the Endosymbiont or Host Small RNA Pathways.

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    Stephanie M Rainey

    2016-04-01

    Full Text Available The intracellular endosymbiotic bacterium Wolbachia can protect insects against viral infection, and is being introduced into mosquito populations in the wild to block the transmission of arboviruses that infect humans and are a major public health concern. To investigate the mechanisms underlying this antiviral protection, we have developed a new model system combining Wolbachia-infected Drosophila melanogaster cell culture with the model mosquito-borne Semliki Forest virus (SFV; Togaviridae, Alphavirus. Wolbachia provides strong antiviral protection rapidly after infection, suggesting that an early stage post-infection is being blocked. Wolbachia does appear to have major effects on events distinct from entry, assembly or exit as it inhibits the replication of an SFV replicon transfected into the cells. Furthermore, it causes a far greater reduction in the expression of proteins from the 3' open reading frame than the 5' non-structural protein open reading frame, indicating that it is blocking the replication of viral RNA. Further to this separation of the replicase proteins and viral RNA in transreplication assays shows that uncoupling of viral RNA and replicase proteins does not overcome Wolbachia's antiviral activity. This further suggests that replicative processes are disrupted, such as translation or replication, by Wolbachia infection. This may occur by Wolbachia mounting an active antiviral response, but the virus did not cause any transcriptional response by the bacterium, suggesting that this is not the case. Host microRNAs (miRNAs have been implicated in protection, but again we found that host cell miRNA expression was unaffected by the bacterium and neither do our findings suggest any involvement of the antiviral siRNA pathway. We conclude that Wolbachia may directly interfere with early events in virus replication such as translation of incoming viral RNA or RNA transcription, and this likely involves an intrinsic (as opposed to

  10. Wolbachia Blocks Viral Genome Replication Early in Infection without a Transcriptional Response by the Endosymbiont or Host Small RNA Pathways.

    Science.gov (United States)

    Rainey, Stephanie M; Martinez, Julien; McFarlane, Melanie; Juneja, Punita; Sarkies, Peter; Lulla, Aleksei; Schnettler, Esther; Varjak, Margus; Merits, Andres; Miska, Eric A; Jiggins, Francis M; Kohl, Alain

    2016-04-01

    The intracellular endosymbiotic bacterium Wolbachia can protect insects against viral infection, and is being introduced into mosquito populations in the wild to block the transmission of arboviruses that infect humans and are a major public health concern. To investigate the mechanisms underlying this antiviral protection, we have developed a new model system combining Wolbachia-infected Drosophila melanogaster cell culture with the model mosquito-borne Semliki Forest virus (SFV; Togaviridae, Alphavirus). Wolbachia provides strong antiviral protection rapidly after infection, suggesting that an early stage post-infection is being blocked. Wolbachia does appear to have major effects on events distinct from entry, assembly or exit as it inhibits the replication of an SFV replicon transfected into the cells. Furthermore, it causes a far greater reduction in the expression of proteins from the 3' open reading frame than the 5' non-structural protein open reading frame, indicating that it is blocking the replication of viral RNA. Further to this separation of the replicase proteins and viral RNA in transreplication assays shows that uncoupling of viral RNA and replicase proteins does not overcome Wolbachia's antiviral activity. This further suggests that replicative processes are disrupted, such as translation or replication, by Wolbachia infection. This may occur by Wolbachia mounting an active antiviral response, but the virus did not cause any transcriptional response by the bacterium, suggesting that this is not the case. Host microRNAs (miRNAs) have been implicated in protection, but again we found that host cell miRNA expression was unaffected by the bacterium and neither do our findings suggest any involvement of the antiviral siRNA pathway. We conclude that Wolbachia may directly interfere with early events in virus replication such as translation of incoming viral RNA or RNA transcription, and this likely involves an intrinsic (as opposed to an induced

  11. Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection.

    Science.gov (United States)

    Pettigrew, Melinda M; Gent, Janneane F; Pyles, Richard B; Miller, Aaron L; Nokso-Koivisto, Johanna; Chonmaitree, Tasnee

    2011-11-01

    Acute otitis media (AOM) is a common complication of upper respiratory tract infection whose pathogenesis involves both viruses and bacteria. We examined risks of acute otitis media associated with specific combinations of respiratory viruses and acute otitis media bacterial pathogens. Data were from a prospective study of children ages 6 to 36 months and included viral and bacterial culture and quantitative PCR for respiratory syncytial virus (RSV), human bocavirus, and human metapneumovirus. Repeated-measure logistic regression was used to assess the relationship between specific viruses, bacteria, and the risk of acute otitis media complicating upper respiratory tract infection. In unadjusted analyses of data from 194 children, adenovirus, bocavirus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were significantly associated with AOM (P virus loads (≥3.16 × 10(7) copies/ml) experienced increased acute otitis media risk. Higher viral loads of bocavirus and metapneumovirus were not significantly associated with acute otitis media. In adjusted models controlling for the presence of key viruses, bacteria, and acute otitis media risk factors, acute otitis media risk was independently associated with high RSV viral load with Streptococcus pneumoniae (odds ratio [OR], 4.40; 95% confidence interval [CI], 1.90 and 10.19) and Haemophilus influenzae (OR, 2.04; 95% CI, 1.38 and 3.02). The risk was higher for the presence of bocavirus and H. influenzae together (OR, 3.61; 95% CI, 1.90 and 6.86). Acute otitis media risk differs by the specific viruses and bacteria involved. Acute otitis media prevention efforts should consider methods for reducing infections caused by respiratory syncytial virus, bocavirus, and adenovirus in addition to acute otitis media bacterial pathogens.

  12. Who Regulates Whom? An Overview of RNA Granules and Viral Infections

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    Natalia Poblete-Durán

    2016-06-01

    Full Text Available After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs, which are translationally silent sites of RNA triage and processing bodies (PBs, which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs.

  13. Who Regulates Whom? An Overview of RNA Granules and Viral Infections

    Science.gov (United States)

    Poblete-Durán, Natalia; Prades-Pérez, Yara; Vera-Otarola, Jorge; Soto-Rifo, Ricardo; Valiente-Echeverría, Fernando

    2016-01-01

    After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis) and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs), which are translationally silent sites of RNA triage and processing bodies (PBs), which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs). PMID:27367717

  14. Evidences for viral strain selection in late stages of HIV infection: an analysis of Vpu alleles.

    Science.gov (United States)

    Gondim, Marcos Vinícius Pereira; da Silva, Joaquim Xavier; Prosdocimi, Francisco; Leonardecz-Neto, Eduardo; Franco, Octávio Luiz; Argañaraz, Enrique Roberto

    2012-02-01

    One of the most studied topics about AIDS disease is the presence of different progression levels in patients infected by HIV. Several studies have shown that this progression is directly associated with host genetics, although viral factors are also known to play a role. Here we explore the contribution of Vpu protein in the evolution of viral population. The sequence variation of Vpu was analyzed during HIV infection in peripheral blood monocyte cells of 12 patients in different clinical stages of HIV-1 infection early and late stages of infections, separated by at least 4 years. The clustering analysis of Vpu sequences showed higher diversity of early alleles, non-random distribution of sequences, and viral evolution strains selection. Forty-two amino acid modifications were found in the multiple alignments of the 57 different alleles found for early stage were 23 modifications were found in the late stage dataset. Interestingly fourteen alteration of early stage were located in conserved site related with Vpu functions alterations while these alterations appear with less frequency in the late stage of infection. Moreover, late stage alleles tend to be similar with the Vpu wild type sequence, suggesting viral selection toward populations harboring more efficient variants during the course of infection. This would contribute to higher infectivity and viral replication actually observed at the aggressive late stages of infection. These data, in conjunction with in vitro experiments, will be important to elucidation of the physiological relevance of Vpu protein in the pathogenic mechanisms of AIDS.

  15. Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice

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    Asquith Kelly L

    2010-02-01

    Full Text Available Abstract Background Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV, increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a species-specific model of RSV and subsequent allergen exposure predisposed to the development of features of asthma. Methods We employed a unique combination of animal models in which BALB/c mice were neonatally infected with pneumonia virus of mice (PVM, which replicates severe RSV disease in human infants and following recovery, were intranasally sensitised with ovalbumin. Animals received low-level challenge with aerosolised antigen for 4 weeks to elicit changes of chronic asthma, followed by a single moderate-level challenge to induce an exacerbation of inflammation. We then assessed airway inflammation, epithelial changes characteristic of remodelling, airway hyperresponsiveness (AHR and host immunological responses. Results Allergic airway inflammation, including recruitment of eosinophils, was prominent only in animals that had recovered from neonatal infection with PVM and then been sensitised and chronically challenged with antigen. Furthermore, only these mice exhibited an augmented Th2-biased immune response, including elevated serum levels of anti-ovalbumin IgE and IgG1 as well as increased relative expression of Th2-associated cytokines IL-4, IL-5 and IL-13. By comparison, development of AHR and mucous cell change were associated with recovery from PVM infection, regardless of subsequent allergen challenge. Increased expression of IL-25, which could contribute to induction of a Th2 response, was demonstrable in the lung following PVM infection. Signalling via the IL-4 receptor α chain was crucial to the development of allergic inflammation, mucous cell change and AHR, because all of these were absent in receptor-deficient mice. In contrast, changes of remodelling were evident in mice

  16. Prophylaxis and therapy of viral infections in pediatric patients treated for malignancy

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    Anna Pegoraro

    2011-02-01

    Full Text Available Infections are still an important cause of mortality and morbidity in pediatric cancer patients. Most of the febrile episodes in immunocompromised patients are classified as a fever of unknown origin (FUO while bacteria are the more frequent causes of documented infections. Viral infections are also feared during chemotherapy but less data are available on their incidence and morbidity. We reviewed the literature on incidence, morbidity, and mortality of viral infections in children undergoing chemotherapy and discussed the evidence concerning the prophylaxis and the therapy.

  17. Perinatal HIV-infection in Sankt Petersburg and Modern Therapy Concomitant Viral Infections

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    V. N. Timchenko

    2016-01-01

    Full Text Available The study included 338 HIV-infected children (B-23 and 350 children with perinatal contact HIV infection (R-75, consisting on the dispensary in the department of maternal and child the St. Petersburg City AIDS Center. In 32 persons (9.5% diagnosed with secondary infections. In the structure of viral opportunistic infections (herpesvirus, SARS amounted to 39.8%, bacterial (bronchitis, tonsillitis, pyoderma, tuberculosis — 34.8%, fungal and parasitic (candidiasis of the oral mucosa, PCP — 25.4 %. Combined therapy (causal, pathogenetic, symptomatic SARS in children with B-23 and R-75, allows you to get in early (6th d. Treatment regress the main symptoms of acute respiratory diseases. Modern therapy of congenital cytomegalovirus infection (VTSMI in children with B-23 and R-75 of the first year of life with antitsitomegalovirusnogo immunoglobulin and preparation of human recombinant interferon alfa-2b in the form of rectal suppositories — VIFERON, causes persistent normalization of clinical and laboratory parameters.

  18. Toward Information Diffusion Model for Viral Marketing in Business

    Directory of Open Access Journals (Sweden)

    Lulwah AlSuwaidan

    2016-02-01

    Full Text Available Current obstacles in the study of social media marketing include dealing with massive data and real-time updates have motivated to contribute solutions that can be adopted for viral marketing. Since information diffusion and social networks are the core of viral marketing, this article aims to investigate the constellation of diffusion methods for viral marketing. Studies on diffusion methods for viral marketing have applied different computational methods, but a systematic investigation of these methods has limited. Most of the literature have focused on achieving objectives such as influence maxi-mization or community detection. Therefore, this article aims to conduct an in-depth review of works related to diffusion for viral marketing. Viral marketing has applied to business-to-consumer transactions but has seen limited adoption in business-to-business transactions. The literature review reveals a lack of new diffusion methods, especially in dynamic and large-scale networks. It also offers insights into applying various mining methods for viral marketing. It discusses some of the challenges, limitations, and future research directions of information diffusion for viral marketing. The article also introduces a viral marketing informa-tion diffusion model. The proposed model attempts to solve the dynamicity and large-scale data of social networks by adopting incremental clustering and a stochastic differential equation for business-to-business transactions.

  19. Human papillomavirus type 16 viral load measurement as a predictor of infection clearance.

    Science.gov (United States)

    Trevisan, Andrea; Schlecht, Nicolas F; Ramanakumar, Agnihotram V; Villa, Luisa L; Franco, Eduardo L

    2013-08-01

    Viral load measurements may predict whether human papillomavirus (HPV) type 16 infections may become persistent and eventually lead to cervical lesions. Today, multiple PCR methods exist to estimate viral load. We tested three protocols to investigate viral load as a predictor of HPV clearance. We measured viral load in 418 HPV16-positive cervical smears from 224 women participating in the Ludwig-McGill Cohort Study by low-stringency PCR (LS-PCR) using consensus L1 primers targeting over 40 known HPV types, and quantitative real-time PCR (qRT-PCR) targeting the HPV16 E6 and L1 genes. HPV16 clearance was determined by MY09/11 and PGMY PCR testing on repeated smears collected over 5 years. Correlation between viral load measurements by qRT-PCR (E6 versus L1) was excellent (Spearman's rank correlation, ρ = 0.88), but decreased for L1 qRT-PCR versus LS-PCR (ρ = 0.61). Viral load by LS-PCR was higher for HPV16 and related types independently of other concurrent HPV infections. Median duration of infection was longer for smears with high copy number by all three PCR protocols (log rank P<0.05). Viral load is inversely related to HPV16 clearance independently of concurrent HPV infections and PCR protocol.

  20. Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: clinical characterization and risk factors for severe disease.

    Science.gov (United States)

    Johnson, Reed F; Dodd, Lori E; Yellayi, Srikanth; Gu, Wenjuan; Cann, Jennifer A; Jett, Catherine; Bernbaum, John G; Ragland, Dan R; St Claire, Marisa; Byrum, Russell; Paragas, Jason; Blaney, Joseph E; Jahrling, Peter B

    2011-12-20

    Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe the pathogenesis of SHFV in rhesus macaques inoculated with doses ranging from 50 PFU to 500,000 PFU. Disease severity was independent of dose with an overall mortality rate of 64% with signs of hemorrhagic fever and multiple organ system involvement. Analyses comparing survivors and non-survivors were performed to identify factors associated with survival revealing differences in the kinetics of viremia, immunosuppression, and regulation of hemostasis. Notable similarities between the pathogenesis of SHFV in NHPs and hemorrhagic fever viruses in humans suggest that SHFV may serve as a suitable model of BSL-4 pathogens.

  1. Differential neutrophil activation in viral infections: Enhanced TLR-7/8-mediated CXCL8 release in asthma

    NARCIS (Netherlands)

    Tang, Francesca S.M.; Van Ly, David; Spann, Kirsten; Reading, Patrick C.; Burgess, Janette K.; Hartl, Dominik; Baines, Katherine J.; Oliver, Brian G.

    2016-01-01

    Background and objective Respiratory viral infections are a major cause of asthma exacerbations. Neutrophils accumulate in the airways and the mechanisms that link neutrophilic inflammation, viral infections and exacerbations are unclear. This study aims to investigate anti-viral responses in neutro

  2. Development of fetal and placental innate immune responses during establishment of persistent infection with bovine viral diarrhea virus.

    Science.gov (United States)

    Smirnova, Natalia P; Webb, Brett T; Bielefeldt-Ohmann, Helle; Van Campen, Hana; Antoniazzi, Alfredo Q; Morarie, Susan E; Hansen, Thomas R

    2012-08-01

    Transplacental viral infections are dependent upon complex interactions between feto-placental and maternal immune responses and the stage of fetal development at which the infection occurs. Bovine viral diarrhea virus (BVDV) has the ability to cross the placenta and infect the fetus. Infection early in gestation with non-cytopathic (ncp) BVDV leads to persistent infection. Establishment of fetal persistent infection results in life-long viremia, virus-specific immunotolerance, and may have detrimental developmental consequences. We have previously shown that heifers infected experimentally with ncp BVDV type 2 on d. 75 of gestation had transient robust up-regulation of the type I interferon (IFN) stimulated genes (ISGs) 3-15 days after viral inoculation. Blood from persistently infected (PI) fetuses, collected 115 days post maternal infection, demonstrated moderate chronic up-regulation of ISGs. This infection model was used to delineate timing of the development of innate immune responses in the fetus and placenta during establishment of persistent infection. It was hypothesized that: (i) chronic stimulation of innate immune responses occurs following infection of the fetus and (ii) placental production of the type I IFN contributes to up-regulation of ISGs in PI fetuses. PI fetuses, generated by intranasal inoculation of pregnant heifers with ncp BVDV, and control fetuses from uninfected heifers, were collected via Cesarean sections on d. 82, 89, 97, 192, and 245 of gestation. Fetal viremia was confirmed starting on d. 89. Significant up-regulation of mRNA encoding cytosolic dsRNA sensors -RIG-I and MDA5 - was detected on d. 82-192. Detection of viral dsRNA by cytosolic sensors leads to the stimulation of ISGs, which was reflected in significant up-regulation of ISG15 mRNA in fetal blood on d. 89, 97, and 192. No difference in IFN-α and IFN-β mRNA concentration was found in fetal blood or caruncular tissue, while a significant increase in both IFN-α and IFN

  3. T Cell Memory in the Context of Persistent Herpes Viral Infections

    Directory of Open Access Journals (Sweden)

    Nicole Torti

    2012-07-01

    Full Text Available The generation of a functional memory T cell pool upon primary encounter with an infectious pathogen is, in combination with humoral immunity, an essential process to confer protective immunity against reencounters with the same pathogen. A prerequisite for the generation and maintenance of long-lived memory T cells is the clearance of antigen after infection, which is fulfilled upon resolution of acute viral infections. Memory T cells play also a fundamental role during persistent viral infections by contributing to relative control and immuosurveillance of active replication or viral reactivation, respectively. However, the dynamics, the phenotype, the mechanisms of maintenance and the functionality of memory T cells which develop upon acute/resolved infection as opposed to chronic/latent infection differ substantially. In this review we summarize current knowledge about memory CD8 T cell responses elicited during α-, β-, and γ-herpes viral infections with major emphasis on the induction, maintenance and function of virus-specific memory CD8 T cells during viral latency and we discuss how the peculiar features of these memory CD8 T cell responses are related to the biology of these persistently infecting viruses.

  4. Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection.

    Science.gov (United States)

    Yang, Qian; Zhang, Qiong; Tang, Jun; Feng, Wen-Hai

    2015-10-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) represents a significantly economical challenge to the swine industry worldwide. In this study, we investigated the importance of cellular and viral lipid rafts in PRRSV infection. First, we demonstrated that PRRSV glycoproteins, Gp3 and Gp4, were associated with lipid rafts during viral entry, and disruption of cellular lipid rafts inhibited PRRSV entry. We also showed the raft-location of CD163, which might contribute to the glycoproteins-raft association. Subsequently, raft disruption caused a significant reduction of viral RNA production. Moreover, Nsp9 was shown to be distributed in rafts, suggesting that rafts probably serve as a platform for PRRSV replication. Finally, we confirmed that disassembly of rafts on the virus envelope may affect the integrity of PRRSV particles and cause the leakage of viral proteins, which impaired PRRSV infectivity. These findings might provide insights on our understanding of the mechanism of PRRSV infection.

  5. No evidence of an increase of bacterial and viral infections following Measles, Mumps and Rubella vaccine.

    Science.gov (United States)

    Stowe, Julia; Andrews, Nick; Taylor, Brent; Miller, Elizabeth

    2009-02-25

    The suggestion that multi-antigen vaccines might overload the immune system has led to calls for single antigen vaccines. In 2003 we showed that rather than an increase there appeared to be a reduced risk of severe bacterial infection in the three months following Measles, Mumps and Rubella vaccine (MMR). The present analysis of illnesses in a general population is based on an additional 10 years of data for bacterial infections and also includes admissions with viral infections. Analyses were carried out using the self-controlled case-series method and separately for bacterial and viral infection cases, using risk periods of 0-30 days, 31-60 days and 61-90 days post MMR vaccine. An analysis was also carried out for those cases which were given MMR and Meningococcal serogroup C (MCC) vaccines concomitantly. A reduced risk was seen in the 0-30-day period for both bacterial infection (relative incidence=0.68, 95% CI 0.54-0.86) and viral infections (relative incidence=0.68, 95% CI 0.49-0.93). There was no increased risk in any period when looking at combined viral or bacterial infections or for individual infections with the single exception of an increased risk in the 31-60 days post vaccination period for herpes infections (relative incidence=1.69, 95% CI 1.06-2.70). For the children given Meningococcal group C vaccines concomitantly no significantly increased risk was seen in either the bacterial (relative incidence=0.54, 95% CI 0.26-1.13) or viral cases (relative incidence=0.46, 95% CI 0.11-1.93). Our study confirms that the MMR vaccine does not increase the risk of invasive bacterial or viral infection in the 90 days after the vaccination and does not support the hypothesis that there is an induced immune deficiency due to overload from multi-antigen vaccines.

  6. Can information be spread as a virus? Viral Marketing as epidemiological model

    CERN Document Server

    Rodrigues, Helena Sofia

    2016-01-01

    In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of the critical factors to this communications strategy effectiveness remain largely unknown, the mathematical models in epidemiology are presented in this marketing specific field. In this paper, an epidemiological model SIR (Susceptible- Infected-Recovered) to study the effects of a viral marketing strategy is presented. It is made a comparison between the disease parameters and the marketing application, and Matlab simulations are performed. Finally, some conclusions are carried out and their marketing implications are e...

  7. Viral and therapeutic control of IFN-β promoter stimulator 1 during hepatitis C virus infection

    Science.gov (United States)

    Loo, Yueh-Ming; Owen, David M.; Li, Kui; Erickson, Andrea K.; Johnson, Cynthia L.; Fish, Penny M.; Carney, D. Spencer; Wang, Ting; Ishida, Hisashi; Yoneyama, Mitsutoshi; Fujita, Takashi; Saito, Takeshi; Lee, William M.; Hagedorn, Curt H.; Lau, Daryl T.-Y.; Weinman, Steven A.; Lemon, Stanley M.; Gale, Michael

    2006-01-01

    Viral signaling through retinoic acid-inducible gene-I (RIG-I) and its adaptor protein, IFN promoter-stimulator 1 (IPS-1), activates IFN regulatory factor-3 (IRF-3) and the host IFN-α/β response that limits virus infection. The hepatitis C virus (HCV) NS3/4A protease cleaves IPS-1 to block RIG-I signaling, but how this regulation controls the host response to HCV is not known. Moreover, endogenous IPS-1 cleavage has not been demonstrated in the context of HCV infection in vitro or in vivo. Here, we show that HCV infection transiently induces RIG-I- and IPS-1-dependent IRF-3 activation. This host response limits HCV production and constrains cellular permissiveness to infection. However, HCV disrupts this response early in infection by NS3/4A cleavage of IPS-1 at C508, releasing IPS-1 from the mitochondrial membrane. Cleavage results in subcellular redistribution of IPS-1 and loss of interaction with RIG-I, thereby preventing downstream activation of IRF-3 and IFN-β induction. Liver tissues from chronically infected patients similarly demonstrate subcellular redistribution of IPS-1 in infected hepatocytes and IPS-1 cleavage associated with a lack of ISG15 expression and conjugation of target proteins in vivo. Importantly, small-molecule inhibitors of NS3/4A prevent cleavage and restore RIG-I signaling of IFN-β induction. Our results suggest a dynamic model in which early activation of IRF-3 and induction of antiviral genes are reversed by IPS-1 proteolysis and abrogation of RIG-I signaling as NS3/4A accumulates in newly infected cells. HCV protease inhibitors effectively prevent IPS-1 proteolysis, suggesting they may be capable of restoring this innate host response in clinical practice. PMID:16585524

  8. Human Lectins and Their Roles in Viral Infections

    Directory of Open Access Journals (Sweden)

    Christopher P. Mason

    2015-01-01

    Full Text Available Innate recognition of virus proteins is an important component of the immune response to viral pathogens. A component of this immune recognition is the family of lectins; pattern recognition receptors (PRRs that recognise viral pathogen-associated molecular patterns (PAMPs including viral glycoproteins. In this review we discuss the contribution of soluble and membrane-associated PRRs to immunity against virus pathogens, and the potential role of these molecules in facilitating virus replication. These processes are illustrated with examples of viruses including human immunodeficiency virus (HIV, hepatitis C virus (HCV and Ebola virus (EBOV. We focus on the structure, function and genetics of the well-characterised C-type lectin mannose-binding lectin, the ficolins, and the membrane-bound CD209 proteins expressed on dendritic cells. The potential for lectin-based antiviral therapies is also discussed.

  9. Bovine viral diarrhea virus infections: manifestations of infection and recent advances in understanding pathogenesis and control.

    Science.gov (United States)

    Brodersen, B W

    2014-03-01

    Bovine viral diarrhea virus (BVDV) continues to be of economic significance to the livestock industry in terms of acute disease and fetal loss. Many of the lesions relating to BVDV infection have been well described previously. The virus is perpetuated in herds through the presence of calves that are persistently infected. Relationships between various species and biotypes of BVDV and host defenses are increasingly understood. Understanding of the host defense mechanisms of innate immunity and adaptive immunity continues to improve, and the effects of the virus on these immune mechanisms are being used to explain how persistent infection develops. The noncytopathic biotype of BVDV plays the major role in its effects on the host defenses by inhibiting various aspects of the innate immune system and creation of immunotolerance in the fetus during early gestation. Recent advances have allowed for development of affordable test strategies to identify and remove persistently infected animals. With these improved tests and removal strategies, the livestock industry can begin more widespread effective control programs.

  10. Early Viral Suppression Improves Neurocognitive Outcomes in HIV-infected Children

    Science.gov (United States)

    CROWELL, Claudia S.; HUO, Yanling; TASSIOPOULOS, Katherine; MALEE, Kathleen M.; YOGEV, Ram; HAZRA, Rohan; RUTSTEIN, Richard M.; NICHOLS, Sharon L.; SMITH, Renee A.; WILLIAMS, Paige L.; OLESKE, James; MULLER, William J.

    2014-01-01

    Objective To estimate the association of age of viral suppression and central nervous system penetration effectiveness (CPE) score with neurocognitive functioning among school-age children with perinatally-acquired HIV infection (PHIV+). Design We analyzed data from two U.S.-based multisite prospective cohort studies. Methods Multivariable general linear regression models were used to evaluate associations of age at viral suppression and CPE scores [of initial ART regimen and weighted average] with WISC-III or WISC-IV neurocognitive assessments [full scale IQ (FSIQ); performance IQ/ perceptual reasoning index (PIQ/PRI); and verbal IQ/ verbal comprehension index (VIQ/VCI)], adjusted for demographic and clinical covariates. Sensitivity analyses were stratified by birth cohort (before vs after 1996). Results 396 PHIV+ children were included. Estimated differences in mean FSIQ (comparing virally suppressed vs. unsuppressed children) by each age cutoff were 3.7, 2.2, 3.2, 4.4, and 3.9 points at ages 1, 2, 3, 4, and 5, respectively. For PIQ/PRI, estimated mean differences were 3.7, 2.4, 2.2, 4.6, and 4.5 at ages 1 through 5 respectively. In both cases, these differences were significant only at the age 4 and 5 thresholds. After stratifying by birth cohort the association between age at suppression and cognitive function persisted only among those born after 1996. Age at viral suppression was not associated with VIQ/VCI; CPE score was not associated with FSIQ, verbal comprehension or perceptual reasoning indices. Conclusions Virologic suppression during infancy or early childhood is associated with improved neurocognitive outcomes in school-aged PHIV+ children. In contrast, CPE scores showed no association with neurocognitive outcomes. PMID:25686678

  11. Comparison of five bacteriophages as models for viral aerosol studies.

    Science.gov (United States)

    Turgeon, Nathalie; Toulouse, Marie-Josée; Martel, Bruno; Moineau, Sylvain; Duchaine, Caroline

    2014-07-01

    Bacteriophages are perceived to be good models for the study of airborne viruses because they are safe to use, some of them display structural features similar to those of human and animal viruses, and they are relatively easy to produce in large quantities. Yet, only a few studies have investigated them as models. It has previously been demonstrated that aerosolization, environmental conditions, and sampling conditions affect viral infectivity, but viral infectivity is virus dependent. Thus, several virus models are likely needed to study their general behavior in aerosols. The aim of this study was to compare the effects of aerosolization and sampling on the infectivity of five tail-less bacteriophages and two pathogenic viruses: MS2 (a single-stranded RNA [ssRNA] phage of the Leviviridae family), Φ6 (a segmented double-stranded RNA [dsRNA] phage of the Cystoviridae family), ΦX174 (a single-stranded DNA [ssDNA] phage of the Microviridae family), PM2 (a double-stranded DNA [dsDNA] phage of the Corticoviridae family), PR772 (a dsDNA phage of the Tectiviridae family), human influenza A virus H1N1 (an ssRNA virus of the Orthomyxoviridae family), and the poultry virus Newcastle disease virus (NDV; an ssRNA virus of the Paramyxoviridae family). Three nebulizers and two nebulization salt buffers (with or without organic fluid) were tested, as were two aerosol sampling devices, a liquid cyclone (SKC BioSampler) and a dry cyclone (National Institute for Occupational Safety and Health two-stage cyclone bioaerosol sampler). The presence of viruses in collected air samples was detected by culture and quantitative PCR (qPCR). Our results showed that these selected five phages behave differently when aerosolized and sampled. RNA phage MS2 and ssDNA phage ΦX174 were the most resistant to aerosolization and sampling. The presence of organic fluid in the nebulization buffer protected phages PR772 and Φ6 throughout the aerosolization and sampling with dry cyclones. In this

  12. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

    Science.gov (United States)

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2015-01-01

    Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

  13. Type-I Interferon responses: From Friend to Foe in the Battle against Chronic Viral Infection

    Directory of Open Access Journals (Sweden)

    Armstrong Murira

    2016-12-01

    Full Text Available Type I interferons (IFN-I have long been heralded as key contributors to effective antiviral responses. More widely understood in the context of acute viral infection, the role of this pleiotropic cytokine has been characterized as triggering antiviral states in cells and potentiating adaptive immune responses. Upon induction in the innate immune response, IFN-I triggers the expression of interferon-stimulated genes (ISGs, which upregulate the effector function of immune cells (e.g., dendritic cells, B cells and T cells towards successful resolution of infections. However, emerging lines of evidence reveal that viral persistence in the course of chronic infections could be driven by deleterious immunomodulatory effects upon sustained IFN-I expression. In this setting, elevation of IFN-I and ISGs is directly correlated to viral persistence and elevated viral loads. It is important to note that the correlation among IFN-I expression, ISGs and viral persistence may be a cause or effect of chronic infection and this is an important distinction to make towards establishing the dichotomous nature of IFN-I responses. The aim of this mini-review is to (i summarize the interaction between IFN-I and downstream effector responses and therefore (ii delineate the function of this cytokine on positive and negative immunoregulation in chronic infection. This is a significant consideration given the current therapeutic administration of IFN-I in chronic viral infections whose therapeutic significance is projected to continue despite emergence of increasingly efficacious antiviral regimens. Furthermore, elucidation of the interplay between virus and the antiviral response in the context of IFN-I will elucidate avenues towards more effective therapeutic and prophylactic measures against chronic viral infections.

  14. 牛病毒性腹泻病毒BVDV2/JZ05-2毒株牛感染模型建立%Bovine Viral Diarrhea Virus BVDV2/JZ05-2 Strain Infection Modeling

    Institute of Scientific and Technical Information of China (English)

    冯卓; 刘艳环; 朱言柱; 李海涛; 钟宏鹏; 王坤; 张润祥; 苗利光

    2013-01-01

    试验用4~6月龄健康牛22头,共分5组,4个试验组5头/组,对照组2头。各试验组分别鼻内接种强毒107 FAID50/mL、106 FAID50/mL、105 FAID50/mL、104 FAID50/mL ,4mL/头,2mL/鼻孔。对照组鼻内接种MDBK细胞培养液冻融物,4mL/头,2mL/鼻孔。试验动物接种强毒后,每天观察实验动物的反应,包括精神状态、体温、食欲、黏膜颜色、呼吸频率、咳嗽、鼻腔分泌物及腹泻等;每天采集鼻拭子用于病毒分离。攻毒前2d、0d ,攻毒后隔天采血用于白细胞计数和病毒分离;试验于病毒接种后14d结束。试验过程中如有动物死亡,对死亡动物进行病理学检查。结果,106.6 FAID50/头BVDV2/JZ05-2攻击4~9月龄的牛,可引起被攻击牛有规律地体温升高和白细胞数量下降,同时可以从鼻拭子中分离到病毒。以这些指标作为感染模型可以有效地评价BVDV2疫苗免疫效果。%The aim of this experiment was to build bovine viral diarrhea virus BVDV 2/JZ05-2 strain infection model .Twenty two healthy cattle (4~6 months old ) were divided into 5 groups .In four experimental groups ,each group had 5 cattle .The control group had 2 cattle .The con-centrations of the BVDV2/JZ05-2 strain used in the experimental groups were 107 FAID50/mL ,106 FAID50/mL ,105 FAID50/mL ,104 FAID50/mL ,respectively .In control group ,the cattle were given MDBK nutrient solution .The volume of the sample was 4 mL through intranasal in dif-ferent groups .After inoculated the strong virus ,the clinical symptom was recorded everyday .The clinical symptom included psychosis ,tempera-ture ,appetite ,mucosa colour ,respiratory rate ,cough ,nasal cavity secreta and diarrhea .Nose swab was collected to separate the strong virus ev-eryday .The blood was obtained to determine white blood cell count and separate virus in -2 day ,0 day and 2 day .After the virus was inoculat-ed for 14 days ,the experiment was finished .If the dead cattle

  15. TCF1 Is Required for the T Follicular Helper Cell Response to Viral Infection

    Directory of Open Access Journals (Sweden)

    Tuoqi Wu

    2015-09-01

    Full Text Available T follicular helper (TFH and T helper 1 (Th1 cells generated after viral infections are critical for the control of infection and the development of immunological memory. However, the mechanisms that govern the differentiation and maintenance of these two distinct lineages during viral infection remain unclear. We found that viral-specific TFH and Th1 cells showed reciprocal expression of the transcriptions factors TCF1 and Blimp1 early after infection, even before the differential expression of the canonical TFH marker CXCR5. Furthermore, TCF1 was intrinsically required for the TFH cell response to viral infection; in the absence of TCF1, the TFH cell response was severely compromised, and the remaining TCF1-deficient TFH cells failed to maintain TFH-associated transcriptional and metabolic signatures, which were distinct from those in Th1 cells. Mechanistically, TCF1 functioned through forming negative feedback loops with IL-2 and Blimp1. Our findings demonstrate an essential role of TCF1 in TFH cell responses to viral infection.

  16. NADPH oxidases (NOXes) and reactive oxygen in viral infections, with emphasis on influenza

    Science.gov (United States)

    The body makes highly reactive molecules, at times as a by-product of other processes, but also sometimes intentionally. This book chapter reviews both the generation of these molecules and how the molecules can impact viral infections. There is a specific focus on influenza virus infections....

  17. Viral infections and cell cycle G2/M regulation

    Institute of Scientific and Technical Information of China (English)

    Richard Y.ZHAO; Robert T.ELDER

    2005-01-01

    Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. In both human and fission yeast(Schizosaccharomyces pombe) cells, the activity of Cdc2 is regulated in part by the phosphorylation status of tyrosine 15(Tyr15) on Cdc2, which is phosphorylated by Wee1 kinase during late G2 and is rapidly dephosphorylated by the Cdc25 tyrosine phosphatase to trigger entry into mitosis. These Cdc2 regulators are the downstream targets of two well-characterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. Increasing evidence suggests that Cdc2 is also commonly targeted by viral proteins,which modulate host cell cycle machinery to benefit viral survival or replication. In this review, we describe the effect of viral protein R (Vpr) encoded by human immunodeficiency virus type 1 (HIV-1) on cell cycle G2/M regulation. Based on our current knowledge about this viral effect, we hypothesize that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. One the unique features distinguishing Vpr-induced G2 arrest from the classic checkpoints is the role of phosphatase 2A (PP2A) in Vpr-induced G2 arrest.Interestingly, PP2A is targeted by a number of other viral proteins including SV40 small T antigen, polyomavirus T antigen, HTLV Tax and adenovirus E4orf4. Thus an in-depth understanding of the molecular mechanisms underlying Vpr-induced G2 arrest will provide additional insights into the basic biology of cell cycle G2/M regulation and into the biological significance of this effect during host-pathogen interactions.

  18. HPV infection, risk factors and viral load among Mexican male college students

    Directory of Open Access Journals (Sweden)

    Carmina Vera-Uehara

    2014-01-01

    Full Text Available Objectives: To determine the prevalence of HPV and the risky sexual behaviors associated to it in a sample of male college students, taking into account genotype and viral load. Methods: From 2002 to 2003, male students from the Autonomous University of Morelos State completed a questionnaire and provided self-collected genital samples to detect and quantify HPV. We performed a bivariate and a multivariate logistic regression analysis to identify correlates associated with the infection and to assess the viral load as a function of the viral infecting type. The fragments of β-globin gene and L1 of HPV, were amplified, purified and cloned, to evaluate viral load. Results: Among 253 subjects, HPV prevalence was 19.4%, and HPV16 was the most common subtype. History of STIs (OR = 4.8; 95% CI 1.2–18.9, contraceptive pill use by female partner (OR = 2.6; 95% CI 1.1–6.3 and exchanging sex for money (OR = 4.9; 95% CI 1.2–20 were associated to the HPV infection. HPV16 viral load was 7.8 copies (HPV/beta-globin compared to 0.9 copies for other HPV types. Discussion: HPV16 displayed the highest viral load, and it was the most prevalent. It was found that using contraceptive pills by female partners was associated with HPV infection.

  19. The host type Ⅰ interferon response to viral and bacterial infections

    Institute of Scientific and Technical Information of China (English)

    Andrea K. PERRY; Gang CHEN; Dahai ZHENG; Hong TANG; Genhong CHENG

    2005-01-01

    Type Ⅰ interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type Ⅰ IFNs are produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN production were largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type Ⅰ IFN during viral infections by recognizing various viral components. Furthermore, much progress has been made in defining the signaling pathways downstream of TLRs for type Ⅰ IFN production. TLR7 and TLR9 have become apparent as universally important in inducing type Ⅰ IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellular viral pattern recognition receptors leading to type Ⅰ IFN production have been identified. Many bacteria can also induce the up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type Ⅰ IFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. This review will discuss the recent advances made in defining the signaling pathways leading to type Ⅰ IFN production.

  20. Metabolomics technology and their application to the study of the viral infection.

    Science.gov (United States)

    Noto, Antonio; Dessi, Angelica; Puddu, Melania; Mussap, Michele; Fanos, Vassilios

    2014-10-01

    In the present review article we have summarized the use of the metabolomics approach to study the metabolic modifications occurring in several bio-fluids due to viral infections. The aim is to highlight the ability of metabolomics to find early fingerprints, which are related to the infections. The (1)H-NMR, UHPLC/MS/MS(2), UPLC/ESI-SYNAPT-HDMS, UPLC-Q-TOF-HDMS analyses were used for the determination of several metabolites representative of the viral infections. The data were analyzed by Principal Component Analysis (PCA), Partial Least Square Discriminant Analysis (PLS-DA) and by regression techniques. The major changes were related to nucleotide, carbohydrates, lipids and amino acid metabolisms. The metabolomics approach could be considered a viable option for characterization of the viral infection and for detecting on going differences in the bio-fluids composition.

  1. Conserved residues in Lassa fever virus Z protein modulate viral infectivity at the level of the ribonucleoprotein.

    Science.gov (United States)

    Capul, Althea A; de la Torre, Juan Carlos; Buchmeier, Michael J

    2011-04-01

    Arenaviruses are negative-strand RNA viruses that cause human diseases such as lymphocytic choriomeningitis, Bolivian hemorrhagic fever, and Lassa hemorrhagic fever. No licensed vaccines exist, and current treatment is limited to ribavirin. The prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is a model for dissecting virus-host interactions in persistent and acute disease. The RING finger protein Z has been identified as the driving force of arenaviral budding and acts as the viral matrix protein. While residues in Z required for viral budding have been described, residues that govern the Z matrix function(s) have yet to be fully elucidated. Because this matrix function is integral to viral assembly, we reasoned that this would be reflected in sequence conservation. Using sequence alignment, we identified several conserved residues in Z outside the RING and late domains. Nine residues were each mutated to alanine in Lassa fever virus Z. All of the mutations affected the expression of an LCMV minigenome and the infectivity of virus-like particles, but to greatly varying degrees. Interestingly, no mutations appeared to affect Z-mediated budding or association with viral GP. Our findings provide direct experimental evidence supporting a role for Z in the modulation of the activity of the viral ribonucleoprotein (RNP) complex and its packaging into mature infectious viral particles.

  2. Association between chronic viral hepatitis infection and breast cancer risk: a nationwide population-based case-control study

    Directory of Open Access Journals (Sweden)

    Su Fu-Hsiung

    2011-11-01

    Full Text Available Abstract Background In Taiwan, there is a high incidence of breast cancer and a high prevalence of viral hepatitis. In this case-control study, we used a population-based insurance dataset to evaluate whether breast cancer in women is associated with chronic viral hepatitis infection. Methods From the claims data, we identified 1,958 patients with newly diagnosed breast cancer during the period 2000-2008. A randomly selected, age-matched cohort of 7,832 subjects without cancer was selected for comparison. Multivariable logistic regression models were constructed to calculate odds ratios of breast cancer associated with viral hepatitis after adjustment for age, residential area, occupation, urbanization, and income. The age-specific ( Results There were no significant differences in the prevalence of hepatitis C virus (HCV infection, hepatitis B virus (HBV, or the prevalence of combined HBC/HBV infection between breast cancer patients and control subjects (p = 0.48. Multivariable logistic regression analysis, however, revealed that age Conclusions HCV infection, but not HBV infection, appears to be associated with early onset risk of breast cancer in areas endemic for HCV and HBV. This finding needs to be replicated in further studies.

  3. Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance.

    Directory of Open Access Journals (Sweden)

    Franz Puttur

    Full Text Available Plasmacytoid dendritic cells (pDCs express the I-type lectin receptor Siglec-H and produce interferon α (IFNα, a critical anti-viral cytokine during the acute phase of murine cytomegalovirus (MCMV infection. The ligands and biological functions of Siglec-H still remain incompletely defined in vivo. Thus, we generated a novel bacterial artificial chromosome (BAC-transgenic "pDCre" mouse which expresses Cre recombinase under the control of the Siglec-H promoter. By crossing these mice with a Rosa26 reporter strain, a representative fraction of Siglec-H⁺ pDCs is terminally labeled with red fluorescent protein (RFP. Interestingly, systemic MCMV infection of these mice causes the downregulation of Siglec-H surface expression. This decline occurs in a TLR9- and MyD88-dependent manner. To elucidate the functional role of Siglec-H during MCMV infection, we utilized a novel Siglec-H deficient mouse strain. In the absence of Siglec-H, the low infection rate of pDCs with MCMV remained unchanged, and pDC activation was still intact. Strikingly, Siglec-H deficiency induced a significant increase in serum IFNα levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFNα production, the control of viral replication was unchanged in vivo. The novel mouse models will be valuable to shed further light on pDC biology in future studies.

  4. In vivo imaging of alphaherpesvirus infection reveals synchronized activity dependent on axonal sorting of viral proteins.

    Science.gov (United States)

    Granstedt, Andrea E; Bosse, Jens B; Thiberge, Stephan Y; Enquist, Lynn W

    2013-09-10

    A clinical hallmark of human alphaherpesvirus infections is peripheral pain or itching. Pseudorabies virus (PRV), a broad host range alphaherpesvirus, causes violent pruritus in many different animals, but the mechanism is unknown. Previous in vitro studies have shown that infected, cultured peripheral nervous system (PNS) neurons exhibited aberrant electrical activity after PRV infection due to the action of viral membrane fusion proteins, yet it is unclear if such activity occurs in infected PNS ganglia in living animals and if it correlates with disease symptoms. Using two-photon microscopy, we imaged autonomic ganglia in living mice infected with PRV strains expressing GCaMP3, a genetically encoded calcium indicator, and used the changes in calcium flux to monitor the activity of many neurons simultaneously with single-cell resolution. Infection with virulent PRV caused these PNS neurons to fire synchronously and cyclically in highly correlated patterns among infected neurons. This activity persisted even when we severed the presynaptic axons, showing that infection-induced firing is independent of input from presynaptic brainstem neurons. This activity was not observed after infections with an attenuated PRV recombinant used for circuit tracing or with PRV mutants lacking either viral glycoprotein B, required for membrane fusion, or viral membrane protein Us9, required for sorting virions and viral glycoproteins into axons. We propose that the viral fusion proteins produced by virulent PRV infection induce electrical coupling in unmyelinated axons in vivo. This action would then give rise to the synchronous and cyclical activity in the ganglia and contribute to the characteristic peripheral neuropathy.

  5. Viral load and short-term natural history of type-specific oncogenic human papillomavirus infections in a high-risk cohort of midadult women.

    Science.gov (United States)

    Winer, Rachel L; Xi, Long Fu; Shen, Zhenping; Stern, Joshua E; Newman, Laura; Feng, Qinghua; Hughes, James P; Koutsky, Laura A

    2014-04-15

    Oncogenic human papillomavirus (HPV) viral load may inform the origin of newly detected infections and characterize oncogenic HPV natural history in midadult women. From 2007 to 2011, we enrolled 521 25-65-year-old-female online daters and followed them triannually with mailed health and sexual behavior questionnaires and kits for self-sampling for PCR-based HPV DNA testing. Samples from oncogenic HPV positive women were selected for type-specific DNA load testing by real-time PCR with adjustment for cellularity. Linear or logistic regression models were used to evaluate relationships between viral levels, health and sexual behavior, and longitudinal oncogenic HPV detection. Type-specific viral levels were borderline significantly higher in oncogenic HPV infections that were prevalent versus newly detected (p = 0.092), but levels in newly detected infections were higher than in infections redetected after intercurrent negativity (p infections detected intermittently, the likelihood of persistent (OR = 4.31, 95% CI: 2.20-8.45) or single-time (OR = 1.32, 95% CI: 1.03-1.71) detection increased per 1-unit increase in baseline log10 viral load. Viral load differences between redetected and newly detected infections suggest a portion of new detections were due to new acquisition, although report of recent new sex partners (a potential marker of new infection) was not predictive of viral load; oncogenic HPV infections in midadult women with new partners likely represent a mix of new acquisition and reactivation or intermittent detection of previous infection. Intermittent detection was characterized by low viral levels, suggesting that intermittent detection of persisting oncogenic HPV infection may be of limited clinical significance. © 2013 UICC.

  6. Experimental infection of reindeer with bovine viral diarrhea virus

    Directory of Open Access Journals (Sweden)

    J.K. Morton

    1990-08-01

    Full Text Available Two 8-month reindeer (Rangifer tarandus and a 1-month-old Hereford-Holstein calf (Bos taurus were inoculated intranasally with the Singer (cytopathogenic strain of bovine viral diarrhea (BVD virus. Clinical signs in reindeer included loose stools containing blood and mucus, and transient laminitis or coronitis. Signs in the calf were limited to bloody mucus in the stool and lesions in the nasal mucosa. Antibody titers to BVD virus in the reindeer were intermittent, and titers in the calf persisted from days 14 to 63 post-inoculation (PI. Viremia was detected on PI day 4 in one reindeer, days 3-7 in the other, and days 2-7 in the calf. Bovine viral diarrhea virus was isolated from the lung of the calf at necropsy (PI day 63.

  7. Possible involvement of maize Rop1 in the defence responses of plants to viral infection.

    Science.gov (United States)

    Cao, Yanyong; Shi, Yan; Li, Yongqiang; Cheng, Yuqin; Zhou, Tao; Fan, Zaifeng

    2012-09-01

    The expression of host genes can be altered during the process of viral infection. To investigate the viral infection-induced up-regulated gene expression changes of maize at different time intervals post-inoculation with Sugarcane mosaic virus (SCMV), a suppression subtractive hybridization cDNA library was constructed. A total of 454 cDNA clones were identified to be viral infection-induced up-regulated genes. The influence of Rop1 on the infection of maize by SCMV was investigated. The results showed that transient silencing of the ZmRop1 gene through virus-induced gene silencing enhanced the accumulation and systemic infection of SCMV and another potyvirus (Pennisetum mosaic virus) in maize plants, whereas transient over-expression of ZmRop1 in maize protoplasts reduced SCMV accumulation. Furthermore, it was demonstrated that the heterologous expression of ZmRop1 impaired Potato virus X infection in Nicotiana benthamiana plants. These data suggest that ZmRop1 may play a role in plant defence responses to viral infection.

  8. Generation of NK cell memory during viral infection

    OpenAIRE

    O’Sullivan, Timothy E.; Sun, Joseph C

    2015-01-01

    Immunological memory is classically regarded as an attribute of antigen-specific T and B-lymphocytes of the adaptive immune system. Cells of the innate immune system, including natural killer (NK) cells, have been considered short-lived cytolytic cells that can rapidly respond against pathogens in an antigen-independent manner, and then die off. However, NK cells have recently been described to possess traits of adaptive immunity, such as clonal expansion after viral antigen exposure to gener...

  9. Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

  10. DMPD: Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune diseases. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18641647 Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune dise... (.csml) Show Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune diseases....iral infection andautoimmune diseases. Authors Gilliet M, Cao W, Liu YJ. Publication Nat Rev Immunol. 2008 A

  11. Multiple functions of DDX3 RNA helicase in gene regulation, tumorigenesis, and viral infection

    OpenAIRE

    2014-01-01

    The DEAD-box RNA helicase DDX3 is a multifunctional protein involved in all aspects of RNA metabolism, including transcription, splicing, mRNA nuclear export, translation, RNA decay and ribosome biogenesis. In addition, DDX3 is also implicated in cell cycle regulation, apoptosis, Wnt-β-catenin signaling, tumorigenesis, and viral infection. Notably, recent studies suggest that DDX3 is a component of anti-viral innate immune signaling pathways. Indeed, DDX3 contributes to enhance the induction ...

  12. HEPATITIS A VIRAL INFECTION TRIGGERS AUTOIMMUNE HEPATITIS IN A PATIENT: A CASE REPORT

    OpenAIRE

    Jakkal Darpan; Solanke Sachin

    2014-01-01

    Hepatitis A virus is an infectious agent known to trigger autoimmune hepatitis (AIH). We present a case in a 40years old woman with Autoimmune hepatitis who presented 4 months after viral hepatits A infection. Diagnosis of hepatitis A virus was attributed on viral serological tests and autoimmune hepatitis (AIH) in accordance with international autoimmune hepatitis group system. [1] She is in remission with steroid therapy. The case we present is unusual with paucity ob...

  13. [Presence of autocomplementary RNA with viral specificity in cells infected with herpes virus].

    Science.gov (United States)

    Béchet, J M; Montagnier, L; Latarjet, R

    1975-01-13

    RNA from cells infected with Herpes simplex virus contain a higher percentage of double-stranded RNA than non-infected cells. This percentage increases three-fold upon self-annealing. The complementary RNA sequences were shown to be virus-specific by the following criteria: (1) high melting temperature than double-stranded RNA from non infected cells; (2) higher density in caesium sulphate; (3) specific hybridization with viral DNA.

  14. Effect of the bovine viral diarrhoea virus (BVDV) infection on dairy calf rearing.

    Science.gov (United States)

    Diéguez, Francisco J; Yus, Eduardo; Vilar, María J; Sanjuán, María L; Arnaiz, Ignacio

    2009-08-01

    The aim of this study was to compare the cumulative incidence of mortality, clinical diarrhoea and respiratory disease in calves, during their first six months of age, in herds with different bovine viral diarrhoea virus (BVDV) infection status. Calves' health indicators were tested by comparing proportions in 101 farms with dissimilar infection condition. The results indicate that there was a significant relationship between the BVDV status (actively infected herd or not) and the cumulative incidence of mortality and respiratory disorders.

  15. [Imported viral infections in international travel; from the virtual to real epidemiology of pandemics].

    Science.gov (United States)

    Jänisch, T; Junghanss, T

    2000-07-15

    Viruses have become more mobile alongside with increasing human mobility and speed of travel. At the same time we get access to information on viral outbreaks and epidemics from large parts of the world faster than ever before. Two recent epidemics will be presented to explore the value and the consequences of communicating epidemiological information through the Internet. The epidemiology, clinical features, diagnostic procedures and prophylaxis of imported viral infections are presented. Risk factors for the emergence and resurgence of viral diseases are being discussed.

  16. Radiometric Methods for Rapid Diagnosis of Viral Infection.

    Science.gov (United States)

    1975-11-01

    4, 6, 24, 48, and 72 hours postinfection, infection time beginning when the 14C-labeled medium was added. Nucleic acid sT, thesis system. Stationary...coccus epidermidis, Pseudomonas aeruginosa, and Acinetobacter caloaceticus var. anitratus) had no effect on the DNA synthesis of HSV-1 infected or...7 UNCLASS 41 RADIOMETRIC METHODS FOR RAPID DIAGNIS F VIRA ~ /fl INFECTION (U) JOHNS HOPKINS UNIV BALTIMORE MDUNC . IFEDH N WAG ER FT AL. NOV 75

  17. iNKT Cells and Their potential Lipid Ligands during Viral Infection

    Directory of Open Access Journals (Sweden)

    Anunya eOpasawatchai

    2015-07-01

    Full Text Available Invariant natural killer T (iNKT cells are a unique population of lipid reactive CD1d restricted innate-like T lymphocytes. Despite being a minor population, they serve as an early source of cytokines and promote immunological crosstalk thus bridging innate and adaptive immunity. Diseases ranging from allergy, autoimmunity, and cancer as well as infectious diseases, including viral infection, have been reported to be influenced by iNKT cells. However, it remains unclear how iNKT cells are activated during viral infection, as virus derived lipid antigens have not been reported. Cytokines may activate iNKT cells during infections from influenza and murine cytomegalovirus (MCMV, although CD1d dependent activation is evident in other viral infections. Several viruses, such as dengue virus (DENV, induce CD1d upregulation which correlates with iNKT cell activation. In contrast, Herpes simplex virus type 1 (HSV-1, Human immunodeficiency virus (HIV, Epstein-Barr virus (EBV and Human papiloma virus (HPV promote CD1d downregulation as a strategy to evade iNKT cell recognition. These observations suggest the participation of a CD1d-dependent process in the activation of iNKT cells in response to viral infection. Endogenous lipid ligands, including phospholipids as well as glycosphingolipids, such as glucosylceramide have been proposed to mediate iNKT cell activation. Pro-inflammatory signals produced during viral infection may stimulate iNKT cells through enhanced CD1d dependent endogenous lipid presentation. Furthermore, viral infection may alter lipid composition and inhibit endogenous lipid degradation. Recent advances in this field are reviewed.

  18. Viral infections during pregnancy and in early life.

    Science.gov (United States)

    Mata, L; Urrutia, J J; Serrato, G; Mohs, E; Chin, T D

    1977-11-01

    There is evidence that fetal antigenic stimulation and intrauterine infection is much more frequent in developing rural populations than in industrialized societies. A similar contrast is observed for postnatal intestinal infection that is significantly greater in the less developed areas. The differences are explained by the divergence in environmental sanitation and personal hygiene. Intestinal infection is important in that diarrheal disease is one of the main factors leading to malnutrition. It is apparent that for developing nations to attain better nutrition, much of the present burden of intestinal infection needs to be controlled.

  19. Dengue virus life cycle : viral and host factors modulating infectivity

    NARCIS (Netherlands)

    Rodenhuis-Zybert, Izabela A.; Wilschut, Jan; Smit, Jolanda M.

    2010-01-01

    Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited de

  20. Dengue virus life cycle : viral and host factors modulating infectivity

    NARCIS (Netherlands)

    Rodenhuis-Zybert, Izabela A.; Wilschut, Jan; Smit, Jolanda M.

    Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited

  1. Viral infection triggers rapid differentiation of human blood monocytes into dendritic cells.

    Science.gov (United States)

    Hou, Wanqiu; Gibbs, James S; Lu, Xiuju; Brooke, Christopher B; Roy, Devika; Modlin, Robert L; Bennink, Jack R; Yewdell, Jonathan W

    2012-03-29

    Surprisingly little is known about the interaction of human blood mononuclear cells with viruses. Here, we show that monocytes are the predominant cell type infected when peripheral blood mononuclear cells are exposed to viruses ex vivo. Remarkably, infection with vesicular stomatitis virus, vaccinia virus, and a variety of influenza A viruses (including circulating swine-origin virus) induces monocytes to differentiate within 18 hours into CD16(-)CD83(+) mature dendritic cells with enhanced capacity to activate T cells. Differentiation into dendritic cells does not require cell division and occurs despite the synthesis of viral proteins, which demonstrates that monocytes counteract the capacity of these highly lytic viruses to hijack host cell biosynthetic capacity. Indeed, differentiation requires infectious virus and viral protein synthesis. These findings demonstrate that monocytes are uniquely susceptible to viral infection among blood mononuclear cells, with the likely purpose of generating cells with enhanced capacity to activate innate and acquired antiviral immunity.

  2. [Consequences of extrahepatic manifestations of hepatitis C viral infection (HCV)].

    Science.gov (United States)

    Pawełczyk, Agnieszka

    2016-04-21

    The hepatitis C virus (HCV) is a primarily hepatotropic virus. However, numerous extrahepatic symptoms are observed in patients chronically infected with HCV, e.g. cryoglobulinemia, lymphoproliferative disorders, kidney diseases, disturbances of the central and peripheral nervous system, thyroid gland, pancreas, lymph nodes and pituitary gland, that develop at various times after the infection. Complex mechanisms underlie these processes, both molecular, related to direct effects of the virus on cells or tissues and indirect mechanisms, resulting from the response of the immune system to infection (via cytokines or oxidative stress), and from the antiviral treatment used. Understanding these mechanisms may contribute to the definition of new prognostic factors, important for the early diagnosis of the infection, which in turn may improve treatment efficacy. This paper is a review of the incidence of selected extrahepatic manifestations of HCV infection and their underlying pathogenetic mechanisms and risk factors.

  3. Quantification of infectious HIV-1 plasma viral load using a boosted in vitro infection protocol.

    Science.gov (United States)

    Rusert, Peter; Fischer, Marek; Joos, Beda; Leemann, Christine; Kuster, Herbert; Flepp, Markus; Bonhoeffer, Sebastian; Günthard, Huldrych F; Trkola, Alexandra

    2004-08-15

    Methods currently used for HIV-1 viral load measurements are very sensitive, but cannot distinguish between infectious and noninfectious particles. Here we describe the development of a novel, sensitive, and highly reproducible method that allows rapid isolation and quantification of infectious particles from patient plasma. By immobilizing HIV-1 particles in human plasma to platelets using polybrene, we observed a 10- to 1000-fold increase in infectivity over infection protocols using free virus particles. Using this method, we evaluated infectivity in plasma from 52 patients at various disease stages. At plasma viral loads of 1000-10000 HIV-1 RNA copies/ml 18%, at 10,000-50,000 copies/ml 73%, at 50,000-100,000 copies/ml 90%, and above 100,000 copies 96% of cultures were positive. We found that infectious titers among patients vary distinctively but are characteristic for a patient over extended time periods. Furthermore, we demonstrate that by evaluating infectious titers in conjunction with total HIV RNA loads, subtle effects of treatment intervention on viremia levels can be detected. The immobilization procedure does not interfere with viral entry and does not restore the infectivity of neutralized virus. Therefore, this assay system can be utilized to investigate the influence of substances that specifically affect virion infectivity such as neutralizing antibodies, soluble CD4, or protease inhibitors. Measuring viral infectivity may thereby function as an additional, useful marker in monitoring disease progression and evaluating efficacy of antivirals in vivo.

  4. Cytotoxic CD4 T Cells—Friend or Foe during Viral Infection?

    Science.gov (United States)

    Juno, Jennifer A.; van Bockel, David; Kent, Stephen J.; Kelleher, Anthony D.; Zaunders, John J.; Munier, C. Mee Ling

    2017-01-01

    CD4 T cells with cytotoxic function were once thought to be an artifact due to long-term in vitro cultures but have in more recent years become accepted and reported in the literature in response to a number of viral infections. In this review, we focus on cytotoxic CD4 T cells in the context of human viral infections and in some infections that affect mice and non-human primates. We examine the effector mechanisms used by cytotoxic CD4 cells, the phenotypes that describe this population, and the transcription factors and pathways that lead to their induction following infection. We further consider the cells that are the predominant targets of this effector subset and describe the viral infections in which CD4 cytotoxic T lymphocytes have been shown to play a protective or pathologic role. Cytotoxic CD4 T cells are detected in the circulation at much higher levels than previously realized and are now recognized to have an important role in the immune response to viral infections. PMID:28167943

  5. Viral Protein Kinetics of Piscine Orthoreovirus Infection in Atlantic Salmon Blood Cells

    Directory of Open Access Journals (Sweden)

    Hanne Merethe Haatveit

    2017-03-01

    Full Text Available Piscine orthoreovirus (PRV is ubiquitous in farmed Atlantic salmon (Salmo salar and the cause of heart and skeletal muscle inflammation. Erythrocytes are important target cells for PRV. We have investigated the kinetics of PRV infection in salmon blood cells. The findings indicate that PRV causes an acute infection of blood cells lasting 1–2 weeks, before it subsides into persistence. A high production of viral proteins occurred initially in the acute phase which significantly correlated with antiviral gene transcription. Globular viral factories organized by the non-structural protein µNS were also observed initially, but were not evident at later stages. Interactions between µNS and the PRV structural proteins λ1, µ1, σ1 and σ3 were demonstrated. Different size variants of µNS and the outer capsid protein µ1 appeared at specific time points during infection. Maximal viral protein load was observed five weeks post cohabitant challenge and was undetectable from seven weeks post challenge. In contrast, viral RNA at a high level could be detected throughout the eight-week trial. A proteolytic cleavage fragment of the µ1 protein was the only viral protein detectable after seven weeks post challenge, indicating that this µ1 fragment may be involved in the mechanisms of persistent infection.

  6. Targeting the IL-33/IL-13 Axis for Respiratory Viral Infections.

    Science.gov (United States)

    Donovan, Chantal; Bourke, Jane E; Vlahos, Ross

    2016-04-01

    Lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are highly prevalent worldwide. One of the major factors that limits the efficacy of current medication in these patients are viral infections, leading to exacerbations of symptoms and decreased quality of life. Current pharmacological strategies targeting virus-induced lung disease are problematic due to antiviral resistance and the requirement for strain-specific vaccination. Thus, new therapeutic strategies are urgently required. In this Opinion article, we provide state-of-the-art evidence from humans and preclinical animal models implicating the interleukin (IL)-33/IL-13 axis in virus-induced lung disease. Thus, targeting the IL-33/IL-13 axis may be a feasible way to overcome the limitations of current therapy used to treat virus-induced exacerbations of lung disease.

  7. Sphingosine kinase 1 serves as a pro-viral factor by regulating viral RNA synthesis and nuclear export of viral ribonucleoprotein complex upon influenza virus infection.

    Directory of Open Access Journals (Sweden)

    Young-Jin Seo

    Full Text Available Influenza continues to pose a threat to humans by causing significant morbidity and mortality. Thus, it is imperative to investigate mechanisms by which influenza virus manipulates the function of host factors and cellular signal pathways. In this study, we demonstrate that influenza virus increases the expression and activation of sphingosine kinase (SK 1, which in turn regulates diverse cellular signaling pathways. Inhibition of SK suppressed virus-induced NF-κB activation and markedly reduced the synthesis of viral RNAs and proteins. Further, SK blockade interfered with activation of Ran-binding protein 3 (RanBP3, a cofactor of chromosome region maintenance 1 (CRM1, to inhibit CRM1-mediated nuclear export of the influenza viral ribonucleoprotein complex. In support of this observation, SK inhibition altered the phosphorylation of ERK, p90RSK, and AKT, which is the upstream signal of RanBP3/CRM1 activation. Collectively, these results indicate that SK is a key pro-viral factor regulating multiple cellular signal pathways triggered by influenza virus infection.

  8. Complexities in Isolation and Purification of Multiple Viruses from Mixed Viral Infections: Viral Interference, Persistence and Exclusion.

    Directory of Open Access Journals (Sweden)

    Naveen Kumar

    Full Text Available Successful purification of multiple viruses from mixed infections remains a challenge. In this study, we investigated peste des petits ruminants virus (PPRV and foot-and-mouth disease virus (FMDV mixed infection in goats. Rather than in a single cell type, cytopathic effect (CPE of the virus was observed in cocultured Vero/BHK-21 cells at 6th blind passage (BP. PPRV, but not FMDV could be purified from the virus mixture by plaque assay. Viral RNA (mixture transfection in BHK-21 cells produced FMDV but not PPRV virions, a strategy which we have successfully employed for the first time to eliminate the negative-stranded RNA virus from the virus mixture. FMDV phenotypes, such as replication competent but noncytolytic, cytolytic but defective in plaque formation and, cytolytic but defective in both plaque formation and standard FMDV genome were observed respectively, at passage level BP8, BP15 and BP19 and hence complicated virus isolation in the cell culture system. Mixed infection was not found to induce any significant antigenic and genetic diversity in both PPRV and FMDV. Further, we for the first time demonstrated the viral interference between PPRV and FMDV. Prior transfection of PPRV RNA, but not Newcastle disease virus (NDV and rotavirus RNA resulted in reduced FMDV replication in BHK-21 cells suggesting that the PPRV RNA-induced interference was specifically directed against FMDV. On long-term coinfection of some acute pathogenic viruses (all possible combinations of PPRV, FMDV, NDV and buffalopox virus in Vero cells, in most cases, one of the coinfecting viruses was excluded at passage level 5 suggesting that the long-term coinfection may modify viral persistence. To the best of our knowledge, this is the first documented evidence describing a natural mixed infection of FMDV and PPRV. The study not only provides simple and reliable methodologies for isolation and purification of two epidemiologically and economically important groups of

  9. Pharmacologic inhibition of COX-1 and COX-2 in influenza A viral infection in mice.

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    Michelle A Carey

    Full Text Available BACKGROUND: We previously demonstrated that cyclooxygenase (COX-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560, a COX-2 inhibitor (celecoxib or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.

  10. Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study

    Science.gov (United States)

    Zhai, Yijie; Franco, Luis M.; Atmar, Robert L.; Quarles, John M.; Arden, Nancy; Bucasas, Kristine L.; Wells, Janet M.; Niño, Diane; Wang, Xueqing; Zapata, Gladys E.; Shaw, Chad A.; Belmont, John W.; Couch, Robert B.

    2015-01-01

    To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. PMID:26070066

  11. Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections--A Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Yijie Zhai

    2015-06-01

    Full Text Available To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55% had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32, other viral infections (N = 4, or no viral agent identified (N = 24. The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment. Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.

  12. Final Technical Report: Viral Infection of Subsurface Microorganisms and Metal/Radionuclide Transport

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Karrie A.; Bender, Kelly S.; Li, Yusong

    2013-09-28

    Microbially mediated metabolisms have been identified as a significant factor either directly or indirectly impacting the fate and transport of heavy metal/radionuclide contaminants. To date microorganisms have been isolated from contaminated environments. Examination of annotated finished genome sequences of many of these subsurface isolates from DOE sites, revealed evidence of prior viral infection. To date the role that viruses play influencing microbial mortality and the resulting community structure which directly influences biogeochemical cycling in soils and sedimentary environments remains poorly understood. The objective of this exploratory study was to investigate the role of viral infection of subsurface bacteria and the formation of contaminant-bearing viral particles. This objective was approached by examining the following working hypotheses: (i) subsurface microorganisms are susceptible to viral infections by the indigenous subsurface viral community, and (ii) viral surfaces will adsorb heavy metals and radionuclides. Our results have addressed basic research needed to accomplish the BER Long Term Measure to provide sufficient scientific understanding such that DOE sites would be able to incorporate coupled physical, chemical and biological processes into decision making for environmental remediation or natural attenuation and long-term stewardship by establishing viral-microbial relationships on the subsequent fate and transport of heavy metals and radionuclides. Here we demonstrated that viruses play a significant role in microbial mortality and community structure in terrestrial subsurface sedimentary systems. The production of viral-like particles within subsurface sediments in response to biostimulation with dissolved organic carbon and a terminal electron acceptor resulted in the production of viral-like particles. Organic carbon alone did not result in significant viral production and required the addition of a terminal electron acceptor

  13. Influence of viral infection on essential oil composition of Ocimum basilicum (Lamiaceae).

    Science.gov (United States)

    Nagai, Alice; Duarte, Ligia M L; Santos, Déborah Y A C

    2011-08-01

    Ocimum basilicum L., popularly known as sweet basil, is a Lamiaceae species whose essential oil is mainly composed of monoterpenes, sesquiterpenes and phenylpropanoids. The contents of these compounds can be affected by abiotic and biotic factors such as infections caused by viruses. The main goal of this research was an investigation of the effects of viral infection on the essential oil profile of common basil. Seeds of O. basilicum L. cv. Genovese were sowed and kept in a greenhouse. Plants presenting two pairs of leaves above the cotyledons were inoculated with an unidentified virus isolated from a field plant showing chlorotic yellow spots and foliar deformation. Essential oils of healthy and infected plants were extracted by hydrodistillation and analyzed by GCMS. Changes in essential oil composition due to viral infection were observed. Methyleugenol and p-cresol,2,6-di-tert-butyl were the main constituents. However, methyleugenol contents were significantly decreased in infected plants.

  14. Detection of markers of hepatitis viral infection in the tissue of bile duct carcinoma

    Institute of Scientific and Technical Information of China (English)

    LIU Hou-bao; QIAN Zhen-yu; WANG Bing-sheng; TONG Sai-xiong

    2008-01-01

    @@ Hepatitis B virus (HBV) is an admitted oncogenic virus. Many epidemiological and molecular biological studies have demonstrated that chronic infection with HBV is a major risk factor associated with the development of hepatocellular carcinoma (HCC) and intrahepatic bile duct cancer.1-4 Compared with hepatocytes and intrahepatic bile duct epithelial cells,extrahepatic bile duct epithelial cells have autoploid in embryogenesis,continuity in anatomy and a similar internal environment.The question arises whether extrahepatic bile duct epithelial cells can receive HBV infection or not? The role of hepatitis viral infection in the pathogenesis of bile duct carcinoma has not yet been clarified.although a causative relationship between HBV or HCV infection and extrahepatic bile duct carcinoma has been reported in the literature.5,6 In this study,we focused on the evidence of hepatitis viral infection in tissue of bile duct carcinoma.

  15. Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein.

    Directory of Open Access Journals (Sweden)

    Simon Swingler

    2007-09-01

    Full Text Available Viruses have evolved strategies to protect infected cells from apoptotic clearance. We present evidence that HIV-1 possesses a mechanism to protect infected macrophages from the apoptotic effects of the death ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand. In HIV-1-infected macrophages, the viral envelope protein induced macrophage colony-stimulating factor (M-CSF. This pro-survival cytokine downregulated the TRAIL receptor TRAIL-R1/DR4 and upregulated the anti-apoptotic genes Bfl-1 and Mcl-1. Inhibition of M-CSF activity or silencing of Bfl-1 and Mcl-1 rendered infected macrophages highly susceptible to TRAIL. The anti-cancer agent Imatinib inhibited M-CSF receptor activation and restored the apoptotic sensitivity of HIV-1-infected macrophages, suggesting a novel strategy to curtail viral persistence in the macrophage reservoir.

  16. dsRNA sensing during viral infection: lessons from plants, worms, insects, and mammals.

    Science.gov (United States)

    de Faria, Isaque João da Silva; Olmo, Roenick Proveti; Silva, Emanuele Guimarães; Marques, João Trindade

    2013-05-01

    Host defense systems often rely on direct and indirect pattern recognition to sense the presence of invading pathogens. Patterns can be molecules directly produced by the pathogen or indirectly generated by changes in host parameters as a consequence of infection. Viruses are intracellular pathogens that hijack the cellular machinery to synthesize their own molecules making direct recognition of viral molecules a great challenge. Antiviral systems in prokaryotes and eukaryotes commonly exploit aberrant nucleic acid sensing to recognize virus infection as host and viral nucleic acid metabolism can greatly differ. Indeed, the generation of dsRNA is often associated with viral infection. In this review, we discuss current knowledge on the mechanisms of viral dsRNA sensing utilized by 2 important antiviral defense systems, RNA interference (RNAi) and the vertebrate immune system. The major viral sensors of the vertebrate immune systems are RIG-like receptors, while RNAi pathways depend on Dicer proteins. These 2 families of sensors share a similar helicase domain with high specificity for dsRNA, which is necessary, but not sufficient for efficient recognition by these receptors. Additional intrinsic features to the dsRNA molecule are also necessary for activation of antiviral systems. Studies utilizing synthetic ligands, in vitro biochemistry and reporter systems have greatly helped increase our knowledge on intrinsic features of dsRNA recognition. However, characteristics such as subcellular localization are extrinsic to the dsRNA itself, but certainly influence the recognition in vivo. Thus, mechanisms of viral dsRNA recognition must address how cellular sensors are recruited to nucleic acids or vice versa. Accessory proteins are likely important for in vivo recognition of extrinsic features of viral RNA, but have mostly remained undiscovered due to the limitations of previous strategies. Hence, the identification of novel components of antiviral systems must take

  17. Viral Infection of the Placenta Leads to Fetal Inflammation and Sensitization to Bacterial Products Predisposing to Preterm Labor

    Science.gov (United States)

    Cardenas, Ingrid; Means, Robert E.; Aldo, Paulomi; Koga, Kaori; Lang, Sabine M.; Booth, Carmen; Manzur, Alejandro; Oyarzun, Enrique; Romero, Roberto; Mor, Gil

    2011-01-01

    Pandemics pose a more significant threat to pregnant women than to the nonpregnant population and may have a detrimental effect on the well being of the fetus. We have developed an animal model to evaluate the consequences of a viral infection characterized by lack of fetal transmission. The experiments described in this work show that viral infection of the placenta can elicit a fetal inflammatory response that, in turn, can cause organ damage and potentially downstream developmental deficiencies. Furthermore, we demonstrate that viral infection of the placenta may sensitize the pregnant mother to bacterial products and promote preterm labor. It is critical to take into consideration the fact that during pregnancy it is not only the maternal immune system responding, but also the fetal/placental unit. Our results further support the immunological role of the placenta and the fetus affecting the global response of the mother to microbial infections. This is relevant for making decisions associated with treatment and prevention during pandemics. PMID:20554966

  18. Comparison on Serum Levels of Procalcitonin of Children with Viral and Bacterial Infection

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Objective To compare and analyze serum levels of procalcitonin (PCT) of children with viral and bacterial infection and probe into the importance of determining the level of serum PCT in the diagnosis of bacterial infection in order to provide evidences of the clinical use of antibiotics. Methods A total of 85 cases of children with an average age of 8.9 years (10 months-12 years) were enrolled in this study, 53 cases were with viral infection and 32 cases with bacterial infection. We determined serum levels of PCT by semi-quantitative solid phase immunoassay, and the serum levels of PCT were divided into four grades as Results The serum level of PCT of the group with bacterial infection were signiifcantly higher than that of the group with viral infection (P Conclusions Serum PCT is a bacterial sensitive marker of bacterial infection in children, and the determination of the level of serum PCT is helpful for the diagnosis of bacterial infection, which can also be a basis for the use of antibiotics.

  19. Memory CD8+ T cell differentiation in viral infection: A cell for all seasons

    Institute of Scientific and Technical Information of China (English)

    Henry Radziewicz; Luke Uebelhoer; Bertram Bengsch; Arash Grakoui

    2007-01-01

    Chronic viral infections such as hepatitis B virus (HBV),hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are major global health problems affecting more than 500 million people worldwide. Virus-specific CD8+ T cells play an important role in the course and outcome of these viral infections and it is hypothesized that altered or impaired differentiation of virusspecific CD8+ T cells contributes to the development of persistence and/or disease progression. A deeper understanding of the mechanisms responsible for functional differentiation of CD8+ T cells is essential for the generation of successful therapies aiming to strengthen the adaptive component of the immune system.

  20. High Serum Lipopolysaccharide-Binding Protein Level in Chronic Hepatitis C Viral Infection Is Reduced by Anti-Viral Treatments

    Science.gov (United States)

    Nien, Hsiao-Ching; Hsu, Shih-Jer; Su, Tung-Hung; Yang, Po-Jen; Sheu, Jin-Chuan; Wang, Jin-Town; Chow, Lu-Ping; Chen, Chi-Ling

    2017-01-01

    Background Lipopolysaccharide-binding protein (LBP) has been reported to associate with metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Since chronic hepatitis C virus (HCV) infection is associated with metabolic derangements, the relationship between LBP and HCV deserves additional studies. This study aimed to determine the serum LBP level in subjects with or without HCV infection and investigate the change of its level after anti-viral treatments with or without interferon. Methods and Findings We recruited 120 non-HCV subjects, 42 and 17 HCV-infected subjects respectively treated with peginterferon α-2a/ribavirin and direct-acting antiviral drugs. Basic information, clinical data, serum LBP level and abdominal ultrasonography were collected. All the subjects provided written informed consent before being enrolled approved by the Research Ethics Committee of the National Taiwan University Hospital. Serum LBP level was significantly higher in HCV-infected subjects than non-HCV subjects (31.0 ± 8.8 versus 20.0 ± 6.4 μg/mL; p-value < 0.001). After multivariate analyses, LBP at baseline was independently associated with body mass index, hemoglobin A1c, alanine aminotransferase (ALT) and HCV infection. Moreover, the baseline LBP was only significantly positively associated with ALT and inversely with fatty liver in HCV-infected subjects. The LBP level significantly decreased at sustained virologic response (27.4 ± 6.6 versus 34.6 ± 7.3 μg/mL, p-value < 0.001; 15.9 ± 4.4 versus 22.2 ± 5.7 μg/mL, p-value = 0.001), regardless of interferon-based or -free therapy. Conclusions LBP, an endotoxemia associated protein might be used as an inflammatory biomarker of both infectious and non-infectious origins in HCV-infected subjects. PMID:28107471

  1. A note on the global properties of an age-structured viral dynamic model with multiple target cell populations.

    Science.gov (United States)

    Wang, Shaoli; Wu, Jianhong; Rong, Libin

    2017-06-01

    Some viruses can infect different classes of cells. The age of infection can affect the dynamics of infected cells and viral production. Here we develop a viral dynamic model with the age of infection and multiple target cell populations. Using the methods of semigroup and Lyapunov function, we study the global asymptotic property of the steady states of the model. The results show that when the basic reproductive number falls below 1, the infection is predicted to die out. When the basic reproductive number exceeds 1, there exists a unique infected steady state which is globally asymptotically stable. The model can be extended to study virus dynamics with multiple compartments or coinfection by multiple types of viruses. We also show that under some scenarios the age-structured model can be reduced to an ordinary differential equation system with or without time delays.

  2. Fatal hepatitis E viral infection in pregnant women in Ghana: a case series

    Directory of Open Access Journals (Sweden)

    Bonney Joseph Humphrey

    2012-09-01

    Full Text Available Abstract Background Viral infections during pregnancy can pose serious threats to mother and fetus from the time of conception to the time of delivery. These lead to congenital defects, spontaneous abortion and even death. The definitive diagnosis and management of pregnancy-related viral infections may be challenging especially in less resourced countries. Case presentation We present clinical and laboratory responses to the diagnosis and management of three cases of fulminant hepatitis secondary to Hepatitis E viral infection in pregnancy. Case 1 was a 31-year-old Ghanaian woman who presented with a week’s history of passing dark urine as well as yellowish discoloration of the eyes. She subsequently developed fulminant hepatitis secondary to Hepatitis E viral infection, spontaneously aborted at 24 weeks of gestation and later died. Case 2 was also a 31-year-old Ghanaian woman who was admitted with a four-day history of jaundice. She had low grade fever, but no history of abdominal pain, haematuria, pale stool or pruritus. She next developed fulminant hepatitis secondary to Hepatitis E viral infection. However, she did not miscarry but died at 28 weeks of gestation. Case 3 was a 17-year-old Ghanaian woman who was referred to the tertiary health facility on account of jaundice and anaemia. She had delivered a live male infant at maturity of 32 weeks but noticed she was jaundiced and had a presentation of active disease 3 days prior to delivery. The baby was icteric at birth and on evaluation, had elevated bilirubin (mixed type with normal liver enzymes. Hepatitis E virus infection was confirmed in both mother and baby. However, the jaundice and the hepatomegaly resolved in mother and baby after 5 and 12 days respectively. Conclusion To the best of our knowledge, these are the first documented cases of fatal fulminant hepatic failures resulting from HEV infection in Ghana.

  3. Host and viral factors contributing to CD8+ T cell failure in hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Christoph Neumann-Haefelin; Hans Christian Spangenberg; Hubert E Blum; Robert Thimme

    2007-01-01

    Virus-specific CD8+ T cells are thought to be the major anti-viral effector cells in hepatitis C virus (HCV)infection. Indeed, viral clearance is associated with vigorous CD8+ T cell responses targeting multiple epitopes. In the chronic phase of infection, HCV-specific CD8+ T cell responses are usually weak, narrowly focused and display often functional defects regarding cytotoxicity, cytokine production, and proliferative capacity. In the last few years, different mechanisms which might contribute to the failure of HCV-specific CD8+ T cells in chronic infection have been identified,including insufficient CD4+ help, deficient CD8+ T cell differentiation, viral escape mutations, suppression by viral factors, inhibitory cytokines, inhibitory ligands, and regulatory T cells. In addition, host genetic factors such as the host's human leukocyte antigen (HLA) background may play an important role in the efficiency of the HCVspecific CD8+ T cell response and thus outcome of infection. The growing understanding of the mechanisms contributing to T cell failure and persistence of HCV infection will contribute to the development of successful immunotherapeutical and -prophylactical strategies.

  4. Induction of tachykinin production in airway epithelia in response to viral infection.

    Directory of Open Access Journals (Sweden)

    James P Stewart

    Full Text Available BACKGROUND: The tachykinins are implicated in neurogenic inflammation and the neuropeptide substance P in particular has been shown to be a proinflammatory mediator. A role for the tachykinins in host response to lung challenge has been previously demonstrated but has been focused predominantly on the release of the tachykinins from nerves innervating the lung. We have previously demonstrated the most dramatic phenotype described for the substance P encoding gene preprotachykinin-A (PPT-A to date in controlling the host immune response to the murine gammaherpesvirus 68, in the lung. METHODOLOGY/PRINCIPAL FINDINGS: In this study we have utilised transgenic mice engineered to co-ordinately express the beta-galactosidase marker gene along with PPT-A to facilitate the tracking of PPT-A expression. Using a combination of these mice and conventional immunohistology we now demonstrate that PPT-A gene expression and substance P peptide are induced in cells of the respiratory tract including tracheal, bronchiolar and alveolar epithelial cells and macrophages after viral infection. This induction was observed 24h post infection, prior to observable inflammation and the expression of pro-inflammatory chemokines in this model. Induced expression of the PPT-A gene and peptide persisted in the lower respiratory tract through day 7 post infection. CONCLUSIONS/SIGNIFICANCE: Non-neuronal PPT-A expression early after infection may have important clinical implications for the progression or management of lung disease or infection aside from the well characterised later involvement of the tachykinins during the inflammatory response.

  5. Induction of Tachykinin Production in Airway Epithelia in Response to Viral Infection

    Science.gov (United States)

    Stewart, James P.; Kipar, Anja; Cox, Helen; Payne, Catherine; Vasiliou, Sylvia; Quinn, John P.

    2008-01-01

    Background The tachykinins are implicated in neurogenic inflammation and the neuropeptide substance P in particular has been shown to be a proinflammatory mediator. A role for the tachykinins in host response to lung challenge has been previously demonstrated but has been focused predominantly on the release of the tachykinins from nerves innervating the lung. We have previously demonstrated the most dramatic phenotype described for the substance P encoding gene preprotachykinin-A (PPT-A) to date in controlling the host immune response to the murine gammaherpesvirus 68, in the lung. Methodology/Principal Findings In this study we have utilised transgenic mice engineered to co-ordinately express the beta-galactosidase marker gene along with PPT-A to facilitate the tracking of PPT-A expression. Using a combination of these mice and conventional immunohistology we now demonstrate that PPT-A gene expression and substance P peptide are induced in cells of the respiratory tract including tracheal, bronchiolar and alveolar epithelial cells and macrophages after viral infection. This induction was observed 24h post infection, prior to observable inflammation and the expression of pro-inflammatory chemokines in this model. Induced expression of the PPT-A gene and peptide persisted in the lower respiratory tract through day 7 post infection. Conclusions/Significance Non-neuronal PPT-A expression early after infection may have important clinical implications for the progression or management of lung disease or infection aside from the well characterised later involvement of the tachykinins during the inflammatory response. PMID:18320026

  6. Viral infection: an evolving insight into the signal transduction pathways responsible for the innate immune response.

    Science.gov (United States)

    Kotwal, Girish J; Hatch, Steven; Marshall, William L

    2012-01-01

    The innate immune response is initiated by the interaction of stereotypical pathogen components with genetically conserved receptors for extracytosolic pathogen-associated molecular patterns (PAMPs) or intracytosolic nucleic acids. In multicellular organisms, this interaction typically clusters signal transduction molecules and leads to their activations, thereby initiating signals that activate innate immune effector mechanisms to protect the host. In some cases programmed cell death-a fundamental form of innate immunity-is initiated in response to genotoxic or biochemical stress that is associated with viral infection. In this paper we will summarize innate immune mechanisms that are relevant to viral pathogenesis and outline the continuing evolution of viral mechanisms that suppress the innate immunity in mammalian hosts. These mechanisms of viral innate immune evasion provide significant insight into the pathways of the antiviral innate immune response of many organisms. Examples of relevant mammalian innate immune defenses host defenses include signaling to interferon and cytokine response pathways as well as signaling to the inflammasome. Understanding which viral innate immune evasion mechanisms are linked to pathogenesis may translate into therapies and vaccines that are truly effective in eliminating the morbidity and mortality associated with viral infections in individuals.

  7. Viral Interleukin-10 Expressed by Human Cytomegalovirus during the Latent Phase of Infection Modulates Latently Infected Myeloid Cell Differentiation ▿ †

    OpenAIRE

    Avdic, Selmir; Cao, John Z.; Cheung, Allen K.L.; Abendroth, Allison; Slobedman, Barry

    2011-01-01

    The human cytomegalovirus UL111A gene is expressed during latent and productive infections, and it codes for homologs of interleukin-10 (IL-10). We examined whether viral IL-10 expressed during latency altered differentiation of latently infected myeloid progenitors. In comparison to infection with parental virus or mock infection, latent infection with a virus in which the gene encoding viral IL-10 has been deleted upregulated cytokines associated with dendritic cell (DC) formation and incre...

  8. [WASTE WATERS AS THE RESERVOIR OF INTESTINAL ENTERIC VIRAL INFECTIONS].

    Science.gov (United States)

    Nedachin, A E; Dmitrieva, R A; Doskina, T V; Dolgin, V A; Chulanov, V P; Pimenov, N N

    2015-01-01

    In the paper there are presented data of field observations of the spectrum of viruses, contained in the waste waters. The studies were performed on the territory of the city and the territory unfavorable for hepatitis A. In the territory of the big city by RT-PCR in the waste liquid the enterovirus RNA was detected in 45% of samples; astroviruses--90%; noroviruses--80% and 15% of rotaviruses. Samples from 2 wells were slightly positive for the presence of HCV RNA A. In the waste liquid on the territory, unfavorable for viral hepatitis A, in 100% of the samples there were determined noro- and astroviruses RNA and adenovirus DNA, in 75%--enterovirus RNA; 50%--HAV RNA and a 25%--rotavirus RNA.

  9. PAR-1 contributes to the innate immune response during viral infection.

    Science.gov (United States)

    Antoniak, Silvio; Owens, A Phillip; Baunacke, Martin; Williams, Julie C; Lee, Rebecca D; Weithäuser, Alice; Sheridan, Patricia A; Malz, Ronny; Luyendyk, James P; Esserman, Denise A; Trejo, JoAnn; Kirchhofer, Daniel; Blaxall, Burns C; Pawlinski, Rafal; Beck, Melinda A; Rauch, Ursula; Mackman, Nigel

    2013-03-01

    Coagulation is a host defense system that limits the spread of pathogens. Coagulation proteases, such as thrombin, also activate cells by cleaving PARs. In this study, we analyzed the role of PAR-1 in coxsackievirus B3-induced (CVB3-induced) myocarditis and influenza A infection. CVB3-infected Par1(-/-) mice expressed reduced levels of IFN-β and CXCL10 during the early phase of infection compared with Par1(+/+) mice that resulted in higher viral loads and cardiac injury at day 8 after infection. Inhibition of either tissue factor or thrombin in WT mice also significantly increased CVB3 levels in the heart and cardiac injury compared with controls. BM transplantation experiments demonstrated that PAR-1 in nonhematopoietic cells protected mice from CVB3 infection. Transgenic mice overexpressing PAR-1 in cardiomyocytes had reduced CVB3-induced myocarditis. We found that cooperative signaling between PAR-1 and TLR3 in mouse cardiac fibroblasts enhanced activation of p38 and induction of IFN-β and CXCL10 expression. Par1(-/-) mice also had decreased CXCL10 expression and increased viral levels in the lung after influenza A infection compared with Par1(+/+) mice. Our results indicate that the tissue factor/thrombin/PAR-1 pathway enhances IFN-β expression and contributes to the innate immune response during single-stranded RNA viral infection.

  10. Global mRNA degradation during lytic gammaherpesvirus infection contributes to establishment of viral latency.

    Directory of Open Access Journals (Sweden)

    Justin M Richner

    2011-07-01

    Full Text Available During a lytic gammaherpesvirus infection, host gene expression is severely restricted by the global degradation and altered 3' end processing of mRNA. This host shutoff phenotype is orchestrated by the viral SOX protein, yet its functional significance to the viral lifecycle has not been elucidated, in part due to the multifunctional nature of SOX. Using an unbiased mutagenesis screen of the murine gammaherpesvirus 68 (MHV68 SOX homolog, we isolated a single amino acid point mutant that is selectively defective in host shutoff activity. Incorporation of this mutation into MHV68 yielded a virus with significantly reduced capacity for mRNA turnover. Unexpectedly, the MHV68 mutant showed little defect during the acute replication phase in the mouse lung. Instead, the virus exhibited attenuation at later stages of in vivo infections suggestive of defects in both trafficking and latency establishment. Specifically, mice intranasally infected with the host shutoff mutant accumulated to lower levels at 10 days post infection in the lymph nodes, failed to develop splenomegaly, and exhibited reduced viral DNA levels and a lower frequency of latently infected splenocytes. Decreased latency establishment was also observed upon infection via the intraperitoneal route. These results highlight for the first time the importance of global mRNA degradation during a gammaherpesvirus infection and link an exclusively lytic phenomenon with downstream latency establishment.

  11. Pattern Recognition Receptors and the Innate Immune Response to Viral Infection

    Directory of Open Access Journals (Sweden)

    Katherine A. Fitzgerald

    2011-06-01

    Full Text Available The innate immune response to viral pathogens is critical in order to mobilize protective immunity. Cells of the innate immune system detect viral infection largely through germline-encoded pattern recognition receptors (PRRs present either on the cell surface or within distinct intracellular compartments. These include the Toll-like receptors (TLRs, the retinoic acid-inducble gene I-like receptors (RLRs, the nucleotide oligomerization domain-like receptors (NLRs, also called NACHT, LRR and PYD domain proteins and cytosolic DNA sensors. While in certain cases viral proteins are the trigger of these receptors, the predominant viral activators are nucleic acids. The presence of viral sensing PRRs in multiple cellular compartments allows innate cells to recognize and quickly respond to a broad range of viruses, which replicate in different cellular compartments. Here, we review the role of PRRs and associated signaling pathways in detecting viral pathogens in order to evoke production of interferons and cytokines. By highlighting recent progress in these areas, we hope to convey a greater understanding of how viruses activate PRR signaling and how this interaction shapes the anti-viral immune response.

  12. Pattern recognition receptors and the innate immune response to viral infection.

    Science.gov (United States)

    Thompson, Mikayla R; Kaminski, John J; Kurt-Jones, Evelyn A; Fitzgerald, Katherine A

    2011-06-01

    The innate immune response to viral pathogens is critical in order to mobilize protective immunity. Cells of the innate immune system detect viral infection largely through germline-encoded pattern recognition receptors (PRRs) present either on the cell surface or within distinct intracellular compartments. These include the Toll-like receptors (TLRs), the retinoic acid-inducble gene I-like receptors (RLRs), the nucleotide oligomerization domain-like receptors (NLRs, also called NACHT, LRR and PYD domain proteins) and cytosolic DNA sensors. While in certain cases viral proteins are the trigger of these receptors, the predominant viral activators are nucleic acids. The presence of viral sensing PRRs in multiple cellular compartments allows innate cells to recognize and quickly respond to a broad range of viruses, which replicate in different cellular compartments. Here, we review the role of PRRs and associated signaling pathways in detecting viral pathogens in order to evoke production of interferons and cytokines. By highlighting recent progress in these areas, we hope to convey a greater understanding of how viruses activate PRR signaling and how this interaction shapes the anti-viral immune response.

  13. THE EXPERIENCE OF ENTECAVIR USE IN PATIENTS WITH HEPATITIS B VIRAL INFECTION ON AN OUTPATIENT BASIS

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    L. I. Mel'nikova

    2015-01-01

    Full Text Available Aim: To evaluate retrospectively the efficacy and safety of entecavir in treatment-naïve patients with hepatitis B viral infection.Materials and methods: Based on patient medical documentation, we analyzed the results of clinical, virologic and instrumental assessment of 36 patients with chronic hepatitis B, 6 of whom were HBeAg-positive, and 1 had a highly active progression of acute hepatitis B. Duration of entecavir therapy (at a dose of 0,5–1 mg daily was 48 weeks.Results: In most patients with chronic hepatitis B, treatment with entecavir, regardless of the HBeAg status, promoted a virologic response (94.4% and HBeAg serum conversion with anti-HBe formation (83.3%, which was associated with a clinical improvement, normalization of liver enzyme activity, reduction of liver fibrosis by 1 point (assessed by fibroelastometry. There were no changes in serum HBsAg during the antiviral therapy. A clinical case of successful entecavir therapy of hepatitis B viral infection is presented. Conclusion: Entecavir is a highly effective and reliable agent that can suppress viral replication in various forms of acute and chronic hepatitis B viral infection. A relatively rapid recurrence of viral replication after withdrawal of the drug justifies further research to optimize treatment of chronic hepatitis B.

  14. DNA methyltransferase DNMT3A associates with viral proteins and impacts HSV-1 infection.

    Science.gov (United States)

    Rowles, Daniell L; Tsai, Yuan-Chin; Greco, Todd M; Lin, Aaron E; Li, Minghao; Yeh, Justin; Cristea, Ileana M

    2015-06-01

    Viral infections can alter the cellular epigenetic landscape, through modulation of either DNA methylation profiles or chromatin remodeling enzymes and histone modifications. These changes can act to promote viral replication or host defense. Herpes simplex virus type 1 (HSV-1) is a prominent human pathogen, which relies on interactions with host factors for efficient replication and spread. Nevertheless, the knowledge regarding its modulation of epigenetic factors remains limited. Here, we used fluorescently-labeled viruses in conjunction with immunoaffinity purification and MS to study virus-virus and virus-host protein interactions during HSV-1 infection in primary human fibroblasts. We identified interactions among viral capsid and tegument proteins, detecting phosphorylation of the capsid protein VP26 at sites within its UL37-binding domain, and an acetylation within the major capsid protein VP5. Interestingly, we found a nuclear association between viral capsid proteins and the de novo DNA methyltransferase DNA (cytosine-5)-methyltransferase 3A (DNMT3A), which we confirmed by reciprocal isolations and microscopy. We show that drug-induced inhibition of DNA methyltransferase activity, as well as siRNA- and shRNA-mediated DNMT3A knockdowns trigger reductions in virus titers. Altogether, our results highlight a functional association of viral proteins with the mammalian DNA methyltransferase machinery, pointing to DNMT3A as a host factor required for effective HSV-1 infection.

  15. Immunosuppression under pregnancy and risks under viral infections

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    O. I. Kiselev

    2013-12-01

    Full Text Available The paper is devoted to studying the mechanisms of combined immunosuppression in pregnant women with influenza infection to develop arrangements for controlling these processes and for decreasing mortality from this infection. In this connection the author is dwelling on the following problems: – How are the fetus immune privilege and tolerance development provided? – What mechanisms do underlie the functional immunosuppresion under pregnancy? – Why are the infections especially dangerous for pregnant women? – Is there the code of the immune system control, and do viruses use this code? The paper deals with the problem of influence of endogenic viruses, which have penetrated the human genome more than 25 million years ago, on the great number of risks of development of various kinds of human pathologies: from infertility to pregnancy diseases; from development of malignant tumors to system pathology and autoimmune diseases.

  16. Ebola Virus Infection Modelling and Identifiability Problems

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    Van-Kinh eNguyen

    2015-04-01

    Full Text Available The recent outbreaks of Ebola virus (EBOV infections have underlined the impact of the virus as a major threat for human health. Due to the high biosafety classification of EBOV (level 4, basic research is very limited. Therefore, the development of new avenues of thinking to advance quantitative comprehension of the virus and its interaction with the host cells is urgently neededto tackle this lethal disease. Mathematical modelling of the EBOV dynamics can be instrumental to interpret Ebola infection kinetics on quantitative grounds. To the best of our knowledge, a mathematical modelling approach to unravel the interaction between EBOV and the host cells isstill missing. In this paper, a mathematical model based on differential equations is used to represent the basic interactions between EBOV and wild-type Vero cells in vitro. Parameter sets that represent infectivity of pathogens are estimated for EBOV infection and compared with influenza virus infection kinetics. The average infecting time of wild-type Vero cells in EBOV is slower than in influenza infection. Simulation results suggest that the slow infecting time of EBOV could be compensated by its efficient replication. This study reveals several identifiability problems and what kind of experiments are necessary to advance the quantification of EBOV infection. A first mathematical approach of EBOV dynamics and the estimation of standard parametersin viral infections kinetics is the key contribution of this work, paving the way for future modelling work on EBOV infection.

  17. Dengue viral infections as a cause of encephalopathy

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    Malavige G

    2007-01-01

    Full Text Available The aim of this study was to determine the clinical characteristics and poor prognostic factors associated with high mortality in dengue encephalopathy. Fifteen patients with confirmed dengue infections, who developed encephalopathy, were recruited from two tertiary care hospitals in Colombo, Sri Lanka. Among the factors that contributed to encephalopathy were: Acute liver failure (73%, electrolyte imbalances (80% and shock (40%. Five (33.3% patients developed seizures. Disseminated intravascular coagulation was seen in five (33.3%. Secondary bacterial infections were observed in 8 (53.3% of our patients. The overall mortality rate was 47%.

  18. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.

    Science.gov (United States)

    Kim, Edy Y; Battaile, John T; Patel, Anand C; You, Yingjian; Agapov, Eugene; Grayson, Mitchell H; Benoit, Loralyn A; Byers, Derek E; Alevy, Yael; Tucker, Jennifer; Swanson, Suzanne; Tidwell, Rose; Tyner, Jeffrey W; Morton, Jeffrey D; Castro, Mario; Polineni, Deepika; Patterson, G Alexander; Schwendener, Reto A; Allard, John D; Peltz, Gary; Holtzman, Michael J

    2008-06-01

    To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of chronic lung disease with pathology that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after an infection with a common type of respiratory virus is cleared to only trace levels of noninfectious virus. Chronic inflammatory disease is generally thought to depend on an altered adaptive immune response. However, here we find that this type of disease arises independently of an adaptive immune response and is driven instead by interleukin-13 produced by macrophages that have been stimulated by CD1d-dependent T cell receptor-invariant natural killer T (NKT) cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a previously undescribed NKT cell-macrophage innate immune axis.

  19. Healthcare-associated viral and bacterial infections in dentistry

    NARCIS (Netherlands)

    Laheij, A.M.G.A.; Kistler, J.O.; Belibasakis, G.N.; Valimaa, H.; de Soet, J.J.

    2012-01-01

    Infection prevention in dentistry is an important topic that has gained more interest in recent years and guidelines for the prevention of cross-transmission are common practice in many countries. However, little is known about the real risks of cross-transmission, specifically in the dental healthc

  20. Viral protein synthesis in cowpea mosaic virus infected protoplasts

    NARCIS (Netherlands)

    Rottier, P.

    1980-01-01

    In contrast to the situation concerning bacterial and, to a lesser extent, animal RNA viruses, little is known about the biochemical processes occurring in plant cells due to plant RNA virus infection. Such processes are difficult to study using intact plants or leaves. Great effort has

  1. Mechanism of action and application of virocids in health care-associated viral infections

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    Babak Shahbaz

    2016-03-01

    Full Text Available Viruses are important causes of acute and chronic diseases in humans. Newer viruses are still being discovered. Apart from frequently causing infections in the general community, many types of viruses are significant nosocomial pathogens that with emerging viruses has become a real issue in medical field. There are specific treatments, vaccine and physical barrier to fight some of these infections. Health care-associated viral infections are an important source of patient’s morbidity and mortality. The method of sterilization or disinfection depends on the intended use of the medical devices (comprising critical, semicritical and noncritical items and failure to perform proper sterilization or disinfection of these items may leads to introduction of viruses, resulting in infection. Disinfection is an essential way in reducing or disruption of transmission of viruses by environmental surfaces, instruments and hands which achieves by chemical disinfectants and antiseptics, respectively. This review discusses about chemical agents with virocids properties (e.g. alcohols, chlorine compounds, formaldehyde, phenolic compounds, glutaraldehyde, ortho-phthaldehyde, hydrogen peroxide, peracetic acid, iodophor, ammonium compounds quaternary, bigunides and so on., mechanisms of action and their applications in health care-associated viral infection control. As well as, we described an overview for hierarchy of viruses in challenge with disinfantans, effective agents on viral inactivation, i.e.targect viruses, viral stability or survival duration time in enviromental surfaces and hands. We explained disinfection of surfaces, challenges in emerging viral pathogens inactivation, viral resistance to chemical disinfectants and antiseptics. Because, there are laboratory studies and clinical evidences for some viruses which viral resistance to biocide or failure to perform proper disinfection can lead to infection outbreaks. Also, we described virucidal

  2. APLASTIC ANEMIA ET CAUSA OF SUSPECT VIRAL HEPATITIS INFECTION: A CASE REPORT

    OpenAIRE

    I Wayan Wawan Lismana

    2014-01-01

    Aplastic anemia is anemia that occurs because of a failure of hematopoiesis is relatively rarebut can be life threatening. The cause of aplastic anemia itself is still largely unknown oridiopathic. Minority of cases mainly due to a virus infection, one of which is viral hepatitishas long been known to cause symptoms of aplastic anemia. This report discusses thesuspected aplastic anemia caused by hepatitis virus infection. Course of the disease or theprognosis of aplastic anemia varies, but a ...

  3. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    Science.gov (United States)

    Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin

    2016-01-01

    Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. PMID:27096199

  4. Incidence of viral infection detected by PCR and real-time PCR in childhood community-acquired pneumonia: a meta-analysis.

    Science.gov (United States)

    Wang, Min; Cai, Feng; Wu, Xiaodong; Wu, Ting; Su, Xin; Shi, Yi

    2015-04-01

    Several studies examining the incidence of viral infection in childhood community-acquired pneumonia (CAP) utilizing polymerase chain reaction (PCR) or real-time PCR methods have been reported. We systematically searched Pubmed and Embase for studies reporting the incidence of respiratory viral infection in childhood CAP. The pooled incidences of viral infection were calculated with a random-effects model. Sources of heterogeneity were explored by subgroup analysis and a univariant metaregression analysis. We included 21 eligible reports in our study. We found significant heterogeneity on the incidence of viral infection in childhood CAP. The random effects pooled incidence was 57.4% (95% confidence interval (CI): 50.8-64.1). The pooled incidence of mixed infection was 29.3% (95%CI: 23.0-35.6) with considerable heterogeneity. The pooled incidence of mixed infection was 29.3% (95%CI: 23.0-35.6). Rhinovirus, respiratory syncytial virus (RSV) and bocavirus were found to be the three most common viruses in childhood CAP. We also demonstrated that respiratory viruses were detected in 76.1% of patients aged ≤ 1 year, 63.1% of patients aged 2-5 years and 27.9% of patients aged ≥ 6 years. We conclude that respiratory viruses are widely detected in paediatric patients with CAP by PCR or real-time PCR methods. More than half of viral infections are probably concurrent with bacterial infections. Rhinovirus, RSV and bocavirus are the three most frequent viruses identified in childhood CAP; the incidence of viral infection decreased with age.

  5. Viral respiratory tract infections among patients with acute undifferentiated fever in Vietnam

    NARCIS (Netherlands)

    H.L. Phuong; T.T.T. Nga; G.J. van Doornum; J. Groen; T.Q. Binh; P.T. Giao; L.Q. Hung; N.V. Nams; P.A. Kager; P.J. de Vries

    2010-01-01

    To investigate the proportion of viral respiratory tract infections among acute undifferentiated fevers (AUFs) at primary health facilities in southern Vietnam during 2001-2005, patients with AUF not caused by malaria were enrolled at twelve primary health facilities and a clinic for malaria control

  6. VIRUS OF HUMAN PAPILLOMA. EPIDEMIOLOGY, LABORATORY DIAGNOSTICS AND PREVENTION OF PAPILLOMA VIRAL INFECTION

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    O. V. Narvskaya

    2011-01-01

    Full Text Available Abstract. The information reflected modern knowledge about virus of human papilloma (VHP and pathogenesis of papilloma viral infection is presented in the lecture. The actual problems of epidemiology, laboratory diagnostics and prevention of VHP associated damage of cervical epithelium have been described.

  7. RESPIRATORY VIRAL-INFECTIONS AGGRAVATE AIRWAY DAMAGE CAUSED BY CHRONIC REJECTION IN RAT LUNG ALLOGRAFTS

    NARCIS (Netherlands)

    WINTER, JB; GOUW, ASH; GROEN, M; WILDEVUUR, C; PROP, J

    1994-01-01

    Airway damage resulting in bronchiolitis obliterans occurs frequently in patients after heart-lung and lung transplantation. Generally, chronic rejection is assumed to be the most important cause of bronchiolitis obliterans. However, viral infections might also be potential causes of airway damage a

  8. Case Report: Emergence of bovine viral diarrhea virus persistently infected calves in a closed herd

    Science.gov (United States)

    Bovine viral diarrhea virus (BVDV) continues to have significant economic impact on the cattle industry worldwide. The virus is primarily maintained in the cattle population due to persistently infected animals. Herd surveillance along with good vaccination programs and biosecurity practices are the...

  9. Resolving bovine viral diarrhea virus subtypes from persistently infected US beef calves with complete genome sequence

    Science.gov (United States)

    Bovine viral diarrhea virus (BVDV) is classified into 2 genotypes, BVDV-1 and BVDV-2, each of which contains distinct subtypes with genetic and antigenic differences. Currently, three major subtypes circulate in the United States: BVDV-1a, 1b, and 2a. In addition, a single case of BVDV-2b infection ...

  10. Comment on ‘Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy’

    Science.gov (United States)

    Darvin, Maxim E.; Lademann, Juergen; Brandt, Nikolay N.

    2016-04-01

    The results of the letter ‘Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy’ authored by Firdous and Anwar (2015 Laser Phys. Lett. 12 085601) are discussed. We show that the original interpretation of the results is not correct and does not correspond to data in the literature.

  11. Effect of natural and ARV-induced viral suppression and viral breakthrough on anti-HIV antibody proportion and avidity in patients with HIV-1 subtype B infection.

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    Sarah K Wendel

    Full Text Available BACKGROUND: Viral suppression and viral breakthrough impact the humoral immune response to HIV infection. We evaluated the impact of viral suppression and viral breakthrough on results obtained with two cross-sectional HIV incidence assays. METHODS: All samples were collected from adults in the US who were HIV infected for >2 years. Samples were tested with the BED capture enzyme immunoassay (BED-CEIA which measures the proportion of IgG that is HIV-specific, and with an antibody avidity assay based on the Genetic Systems 1/2+ O ELISA. We tested 281 samples: (1 30 samples from 18 patients with natural control of HIV-1 infection known as elite controllers or suppressors (2 72 samples from 18 adults on antiretroviral therapy (ART, with 1 sample before and 2-6 samples after ART initiation, and (3 179 samples from 20 virally-suppressed adults who had evidence of viral breakthrough receiving ART (>400 copies/ml HIV RNA and with subsequent viral suppression. RESULTS: For elite suppressors, 10/18 had BED-CEIA values <0.8 normalized optical density units (OD-n and these values did not change significantly over time. For patients receiving ART, 14/18 had BED-CEIA values that decreased over time, with a median decrease of 0.42 OD-n (range 0.10 to 0.63/time point receiving ART. Three patterns of BED-CEIA values were observed during viral breakthrough: (1 values that increased then returned to pre-breakthrough values when viral suppression was re-established, (2 values that increased after viral breakthrough, and (3 values that did not change with viral breakthrough. CONCLUSIONS: Viral suppression and viral breakthrough were associated with changes in BED-CEIA values, reflecting changes in the proportion of HIV-specific IgG. These changes can result in misclassification of patients with long-term HIV infection as recently infected using the BED-CEIA, thereby influencing a falsely high value for cross-sectional incidence estimates.

  12. The importance of bacterial and viral infections associated with adult asthma exacerbations in clinical practice.

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    Motoyasu Iikura

    Full Text Available Viral infection is one of the risk factors for asthma exacerbation. However, which pathogens are related to asthma exacerbation in adults remains unclear.The relation between various infections and adult asthma exacerbations was investigated in clinical practice.The study subjects included 50 adult inpatients due to asthma exacerbations and 20 stable outpatients for comparison. The pathogens from a nasopharyngeal swab were measured by multiplex PCR analysis.Asthma exacerbations occurred after a common cold in 48 inpatients. The numbers of patients with viral, bacterial, or both infections were 16, 9, and 9, respectively. The dominant viruses were rhinoviruses, respiratory syncytial virus, influenza virus, and metapneumovirus. The major bacteria were S. pneumoniae and H. influenzae. Compared to pathogen-free patients, the patients with pathogens were older and non-atopic and had later onset of disease, lower FeNO levels, lower IgE titers, and a higher incidence of comorbid sinusitis, COPD, or pneumonia. Compared to stable outpatients, asthma exacerbation inpatients had a higher incidence of smoking and comorbid sinusitis, COPD, or pneumonia. Viruses were detected in 50% of stable outpatients, but a higher incidence of rhinovirus, respiratory syncytial virus, and metapneumovirus infections was observed in asthma exacerbation inpatients. H. influenzae was observed in stable asthmatic patients. Other bacteria, especially S. pneumoniae, were important in asthma exacerbation inpatients.Viral or bacterial infections were observed in 70% of inpatients with an asthma exacerbation in clinical practice. Infection with S. pneumoniae was related to adult asthma exacerbation.

  13. Viral quasispecies.

    Science.gov (United States)

    Andino, Raul; Domingo, Esteban

    2015-05-01

    New generation sequencing is greatly expanding the capacity to examine the composition of mutant spectra of viral quasispecies in infected cells and host organisms. Here we review recent progress in the understanding of quasispecies dynamics, notably the occurrence of intra-mutant spectrum interactions, and implications of fitness landscapes for virus adaptation and de-adaptation. Complementation or interference can be established among components of the same mutant spectrum, dependent on the mutational status of the ensemble. Replicative fitness relates to an optimal mutant spectrum that provides the molecular basis for phenotypic flexibility, with implications for antiviral therapy. The biological impact of viral fitness renders particularly relevant the capacity of new generation sequencing to establish viral fitness landscapes. Progress with experimental model systems is becoming an important asset to understand virus behavior in the more complex environments faced during natural infections.

  14. Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

    Science.gov (United States)

    Alcendor, Donald J

    2017-07-15

    Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study.

  15. Toscana meningoencephalitis: a comparison to other viral central nervous system infections

    Science.gov (United States)

    Jaijakul, Siraya; Arias, Cesar A.; Hossein, Monir; Arduino, Roberto C.; Wootton, Susan H.; Hasbun, Rodrigo

    2012-01-01

    Background Toscana virus (TOSV) is an emerging pathogen causing central nervous system (CNS) infection in Mediterranean countries, mostly during summer season. Objectives To compare the clinical and laboratory characteristics of Toscana CNS infections to the most common viral pathogens seen in the United States. Study Design We performed a case series of patients with 41 TOSV infection and compared the clinical characteristics, laboratory findings, imaging results and clinical outcomes to the most commonly recognized viral causes of meningoencephalitis in the US (enterovirus (n=60), herpes simplex virus (n=48), and west nile virus (n=30) from our multi-center study of patients with aseptic meningoencephalitis syndromes in the Greater Houston area. Results TOSV infection occurs in different age groups compared to enterovirus, HSV, and WNV. All infections most frequently occur during summer-fall except HSV which distributes throughout the year. All patients with TOSV had history of travel to endemic areas. There are differences in clinical presentation and CSF findings comparing TOSV and enterovirus, HSV, and WNV infection. There are no significant differences in outcomes of each infection except WNV meningoencephalitis which had a poorer outcome compared to TOSV infection. Conclusions TOSV is an emerging pathogen that should be considered in the differential diagnosis of patients with CNS infections and a recent travel history to endemic areas. PMID:22867730

  16. Fibrillary glomerulonephritis with hepatitis C viral infection and hypocomplementemia.

    Science.gov (United States)

    Ray, Susan; Rouse, Kelly; Appis, Andrew; Novak, Robert; Haller, Nairmeen Awad

    2008-01-01

    Fibrillary glomerulonephritis (FGN) is a relatively rare cause of renal disease, found in only 0.6-1.5% of native renal biopsies. The pathogenesis of FGN is not well described, and very few associations with disease processes other than hepatitis C virus (HCV) have been made. We describe a case that provides evidence in support of the FGN-HCV association, as well as introduces the association of FGN-HCV and hypocomplementemia. The case is a 53-year-old African-American female demonstrating a classical presentation of FGN complicated by a concomitant HCV infection. Treating an HCV infection with alpha-interferon has been shown to result in subsequent improvement in the nephrotic syndrome and renal function. However, this patient is unique in that she is complicated with hypocomplementemia, creating a complex treatment situation.

  17. Perinatal Exposure to Environmental Tobacco Smoke (ETS Enhances Susceptibility to Viral and Secondary Bacterial Infections

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    Jocelyn A. Claude

    2012-10-01

    Full Text Available Studies suggest childhood exposure to environmental tobacco smoke (ETS leads to increased incidence of infections of the lower respiratory tract. The objective of this study was to determine whether perinatal exposure to ETS increases the incidence, morbidity and severity of respiratory influenza infection and whether a secondary bacterial challenge at the peak of a pre-existing viral infection creates an enhanced host-pathogen susceptibility to an opportunistic infection. Timed-pregnant female Balb/c mice were exposed to either ETS for 6 h/day, 7 d/week beginning on gestation day 14 and continuing with the neonates to 6 weeks of age. Control animals were exposed to filtered air (FA. At the end of exposure, mice were intranasally inoculated with a murine-adapted influenza A. One week later, an intranasal inoculation of S. aureus bacteria was administered. The respective treatment groups were: bacteria only, virus only or virus+bacteria for both FA and ETS-exposed animals for a total of six treatment groups. Animal behavior and body weights were documented daily following infection. Mice were necropsied 1-day post-bacterial infection. Bronchoalveolar lavage fluid (BALF cell analysis demonstrated perinatal exposure to ETS, compared to FA, leads to delayed but enhanced clinical symptoms and enhanced total cell influx into the lungs associated with viral infection followed by bacterial challenge. Viral infection significantly increases the number of neutrophils entering the lungs following bacterial challenge with either FA or ETS exposure, while the influx of lymphocytes and monocytes is significantly enhanced only by perinatal ETS exposure. There is a significant increase in peribronchiolar inflammation following viral infection in pups exposed to ETS compared with pups exposed to FA, but no change is noted in the degree of lung injury between FA and ETS-exposed animals following bacterial challenge. The data suggests perinatal exposure to ETS

  18. Heteropolymers: A New Class of Therapeutics for Treating Lethal Bacterial and Viral Infections

    Science.gov (United States)

    2004-11-17

    tularensis (Tularemia) • Clostridium botulinum • Poxviruses (Smallpox) • Viral hemorrhagic fevers Filoviruses (Ebola, Marburg) Arenaviruses...viral challenges we developed challenge models in a transgenic mouse (TgN hCR1) that expresses human CR1 on the surface of their RBCs.6 While mice...Klickstein L., Spitalny G. L., Finberg R. W. 2004. A transgenic mouse model for studying the clearance of blood-borne pathogens via human complement receptor

  19. Chikungunya fever: A re-emerging viral infection

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    Chhabra M

    2008-01-01

    Full Text Available Chikungunya (CHIK fever is a re-emerging viral disease characterized by abrupt onset of fever with severe arthralgia followed by constitutional symptoms and rash lasting for 1-7 days. The disease is almost self-limiting and rarely fatal. Chikungunya virus (CHIKV is a RNA virus belonging to family Togaviridae, genus Alphavirus. Molecular characterization has demonstrated two distinct lineages of strains which cause epidemics in Africa and Asia. These geographical genotypes exhibit differences in the transmission cycles. In contrast to Africa where sylvatic cycle is maintained between monkeys and wild mosquitoes, in Asia the cycle continues between humans and the Aedes aegypti mosquito. CHIKV is known to cause epidemics after a period of quiescence. The first recorded epidemic occurred in Tanzania in 1952-1953. In Asia, CHIK activity was documented since its isolation in Bangkok, Thailand in 1958. Virus transmission continued till 1964. After hiatus, the virus activity re-appeared in the mid-1970s and declined by 1976. In India, well-documented outbreaks occurred in 1963 and 1964 in Kolkata and southern India, respectively. Thereafter, a small outbreak of CHIK was reported from Sholapur district, Maharashtra in 1973. CHIKV emerged in the islands of South West Indian Ocean viz. French island of La Reunion, Mayotee, Mauritius and Seychelles which are reporting the outbreak since February, 2005. After quiescence of about three decades, CHIKV re-emerged in India in the states of Andhra Pradesh, Karnataka, Maharashtra, Madhya Pradesh and Tamil Nadu since December, 2005. Cases have also been reported from Rajasthan, Gujarat and Kerala. The outbreak is still continuing. National Institute of Communicable Diseases has conducted epidemiological, entomological and laboratory investigations for confirmation of the outbreak. These have been discussed in detail along with the major challenges that the country faced during the current outbreak.

  20. Physical status and viral load in women with positive human papillomavirus (HPV) infection in uterine cervix

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byoung Gie; Lee, Eui Don; Zin, Yong Jae [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    This study was performed to determine the frequency of viral integration and viral load in women with positive HPV type 16 infection, and showing normal findings, CIN, and cervical cancer. Total 75 (normal, 15; CIN I, 20; CIN III, 20; cervical cancer, 20) cervical swab specimens were used. HPV detection, typing, and viral load was determined by PCR method. Seventy of 75 (93.3%) of cervical swab specimens showed same results with hybrid capture assay and PCR method for detecting HPV DNA. HPV type 16 DNA was identified more frequently with progression from normal to cervical cancer (normal, 13 %; CIN I, 15%; CIN III, 40 %; cervical cancer, 55 %). The frequency of HPV type 16 DNA integration also increased with grade of the lesion (normal, 0 %; CIN I, 33 %; CIN III, 87 %; cervical cancer, 91 %) suggesting most of HPV type 16 present as integration forms in the cells. In addition, high-level of HPV 16 viral load also was found more frequently in CIN III and cervical cancer (normal, 0 %; CIN I, 0 %; CIN III, 87 %; cervical cancer, 100 %). These results suggest that viral integration and high-level of viral load may play an important role in cervical carcinogenesis. (author). 13 refs., 5 figs.

  1. The ins and outs of eukaryotic viruses: Knowledge base and ontology of a viral infection

    Science.gov (United States)

    Hulo, Chantal; Masson, Patrick; de Castro, Edouard; Auchincloss, Andrea H.; Foulger, Rebecca; Poux, Sylvain; Lomax, Jane; Bougueleret, Lydie; Xenarios, Ioannis

    2017-01-01

    Viruses are genetically diverse, infect a wide range of tissues and host cells and follow unique processes for replicating themselves. All these processes were investigated and indexed in ViralZone knowledge base. To facilitate standardizing data, a simple ontology of viral life-cycle terms was developed to provide a common vocabulary for annotating data sets. New terminology was developed to address unique viral replication cycle processes, and existing terminology was modified and adapted. The virus life-cycle is classically described by schematic pictures. Using this ontology, it can be represented by a combination of successive terms: “entry”, “latency”, “transcription”, “replication” and “exit”. Each of these parts is broken down into discrete steps. For example Zika virus “entry” is broken down in successive steps: “Attachment”, “Apoptotic mimicry”, “Viral endocytosis/ macropinocytosis”, “Fusion with host endosomal membrane”, “Viral factory”. To demonstrate the utility of a standard ontology for virus biology, this work was completed by annotating virus data in the ViralZone, UniProtKB and Gene Ontology databases. PMID:28207819

  2. Hepatitis C viral infection in a Chinese hemodialysis unit

    Institute of Scientific and Technical Information of China (English)

    LI Han; WANG Shi-xiang

    2010-01-01

    Background The prevalence of hepatitis C virus (HCV) infection among maintenance hemodialysis (MHD) patients varies among countries and among dialysis units within a single country. The present study aimed to investigate the prevalence and characteristics of HCV infection in MHD patients in a Chinese hemodialysis unit.Methods One hundred and ninety-two patients on MHD for an average of (86.1±30.0) months (range 6-181 months) were enrolled in this cross-sectional study. HCV antibody and HCV-RNA were measured in these MHD patients before hemodialysis by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods.According to the result, all the patients were then divided into two groups: GroupⅠwas positive for HCV antibody and/or HCV-RNA (n=32), and Group Ⅱ was negative for HCV antibody and HCV-RNA (n=160). The following information was obtained for all the patients: socio-demographic data, history of blood transfusions and kidney transplantation, and some laboratory values. The MHD patients who were positive for HCV antibody and/or HCV-RNA were followed for more than three years. The disease activities were graded into "asymptomatic" if alanine aminotransferase (ALT) was less than 40 U/L,"low activities" if ALT was 40-79 U/L, and "high activities" if ALT was equal to or above 80 U/L.Results The prevalence of HCV infection in MHD patients in our dialysis unit in May 2009 was 16.7, which was significantly higher than in general population (3.2%). Among the 32 MHD patients with HCV positive, 20 patients were positive for HCV antibody but negative for HCV-RNA, eight patients were positive both for HCV antibody and HCV-RNA,four patients were negative for HCV antibody but positive for HCV-RNA. Eleven patients had a history of kidney transplantation and 12 had a history of blood transfusion, which were significantly more than among the MHD patients without HCV. Thirty of the 32 MHD patients were asymptomatic. There were no significant

  3. Detection of high biliary and fecal viral loads in patients with chronic hepatitis C virus infection.

    Science.gov (United States)

    Monrroy, Hugo; Angulo, Jenniffer; Pino, Karla; Labbé, Pilar; Miquel, Juan Francisco; López-Lastra, Marcelo; Soza, Alejandro

    2017-05-01

    The life cycle of the hepatitis C virus (HCV) is closely associated with lipid metabolism. Recently, NPC1L1 (a cholesterol transporter) has been reported to function as an HCV receptor. This receptor is expressed in the hepatocyte canalicular membrane and in the intestine; serving as a key transporter for the cholesterol enterohepatic cycle. We hypothesized that HCV might have a similar cycle, so we aimed to study the presence of HCV in bile and stools of infected patients. Blood, feces, and duodenal bile samples were collected from patients infected with HCV. The biliary viral load was normalized to the bile salt concentration of each sample and the presence of HCV core protein was also evaluated. A total of 12 patients were recruited. HCV RNA was detected in the bile from ten patients. The mean viral load was 2.5log10IU/60mg bile salt. In the stool samples, HCV RNA was detected in ten patients (mean concentration 2.7log10IU/g of feces). HCV RNA is readily detectable and is present at relatively high concentrations in the bile and stool samples of infected patients. This may be relevant as a source of infection in men who have sex with men. Biliary HCV secretion may perhaps play a role in the persistence of viral infection via an enterohepatic cycle of the virus or intrahepatic spread. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  4. The Incubation Period of Primary Epstein-Barr Virus Infection: Viral Dynamics and Immunologic Events.

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    Samantha K Dunmire

    2015-12-01

    Full Text Available Epstein-Barr virus (EBV is a human herpesvirus that causes acute infectious mononucleosis and is associated with cancer and autoimmune disease. While many studies have been performed examining acute disease in adults following primary infection, little is known about the virological and immunological events during EBV's lengthy 6 week incubation period owing to the challenge of collecting samples from this stage of infection. We conducted a prospective study in college students with special emphasis on frequent screening to capture blood and oral wash samples during the incubation period. Here we describe the viral dissemination and immune response in the 6 weeks prior to onset of acute infectious mononucleosis symptoms. While virus is presumed to be present in the oral cavity from time of transmission, we did not detect viral genomes in the oral wash until one week before symptom onset, at which time viral genomes were present in high copy numbers, suggesting loss of initial viral replication control. In contrast, using a sensitive nested PCR method, we detected viral genomes at low levels in blood about 3 weeks before symptoms. However, high levels of EBV in the blood were only observed close to symptom onset-coincident with or just after increased viral detection in the oral cavity. These data imply that B cells are the major reservoir of virus in the oral cavity prior to infectious mononucleosis. The early presence of viral genomes in the blood, even at low levels, correlated with a striking decrease in the number of circulating plasmacytoid dendritic cells well before symptom onset, which remained depressed throughout convalescence. On the other hand, natural killer cells expanded only after symptom onset. Likewise, CD4+ Foxp3+ regulatory T cells decreased two fold, but only after symptom onset. We observed no substantial virus specific CD8 T cell expansion during the incubation period, although polyclonal CD8 activation was detected in

  5. Viral Metagenomics on Animals as a Tool for the Detection of Zoonoses Prior to Human Infection?

    Directory of Open Access Journals (Sweden)

    Sarah Temmam

    2014-06-01

    Full Text Available Many human viral infections have a zoonotic, i.e., wild or domestic animal, origin. Several zoonotic viruses are transmitted to humans directly via contact with an animal or indirectly via exposure to the urine or feces of infected animals or the bite of a bloodsucking arthropod. If a virus is able to adapt and replicate in its new human host, human-to-human transmissions may occur, possibly resulting in an epidemic, such as the A/H1N1 flu pandemic in 2009. Thus, predicting emerging zoonotic infections is an important challenge for public health officials in the coming decades. The recent development of viral metagenomics, i.e., the characterization of the complete viral diversity isolated from an organism or an environment using high-throughput sequencing technologies, is promising for the surveillance of such diseases and can be accomplished by analyzing the viromes of selected animals and arthropods that are closely in contact with humans. In this review, we summarize our current knowledge of viral diversity within such animals (in particular blood-feeding arthropods, wildlife and domestic animals using metagenomics and present its possible future application for the surveillance of zoonotic and arboviral diseases.

  6. Viral metagenomics on animals as a tool for the detection of zoonoses prior to human infection?

    Science.gov (United States)

    Temmam, Sarah; Davoust, Bernard; Berenger, Jean-Michel; Raoult, Didier; Desnues, Christelle

    2014-06-10

    Many human viral infections have a zoonotic, i.e., wild or domestic animal, origin. Several zoonotic viruses are transmitted to humans directly via contact with an animal or indirectly via exposure to the urine or feces of infected animals or the bite of a bloodsucking arthropod. If a virus is able to adapt and replicate in its new human host, human-to-human transmissions may occur, possibly resulting in an epidemic, such as the A/H1N1 flu pandemic in 2009. Thus, predicting emerging zoonotic infections is an important challenge for public health officials in the coming decades. The recent development of viral metagenomics, i.e., the characterization of the complete viral diversity isolated from an organism or an environment using high-throughput sequencing technologies, is promising for the surveillance of such diseases and can be accomplished by analyzing the viromes of selected animals and arthropods that are closely in contact with humans. In this review, we summarize our current knowledge of viral diversity within such animals (in particular blood-feeding arthropods, wildlife and domestic animals) using metagenomics and present its possible future application for the surveillance of zoonotic and arboviral diseases.

  7. Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity

    Energy Technology Data Exchange (ETDEWEB)

    Knipe, David M., E-mail: david_knipe@hms.harvard.edu

    2015-05-15

    Herpes simplex virus (HSV) undergoes a lytic infection in epithelial cells and a latent infection in neuronal cells, and epigenetic mechanisms play a major role in the differential gene expression under the two conditions. HSV viron DNA is not associated with histones but is rapidly loaded with heterochromatin upon entry into the cell. Viral proteins promote reversal of the epigenetic silencing in epithelial cells while the viral latency-associated transcript promotes additional heterochromatin in neuronal cells. The cellular sensors that initiate the chromatinization of foreign DNA have not been fully defined. IFI16 and cGAS are both essential for innate sensing of HSV DNA, and new evidence shows how they work together to initiate innate signaling. IFI16 also plays a role in the heterochromatinization of HSV DNA, and this review will examine how IFI16 integrates epigenetic regulation and innate sensing of foreign viral DNA to show how these two responses are related. - Highlights: • HSV lytic and latent gene expression is regulated differentially by epigenetic processes. • The sensors of foreign DNA have not been defined fully. • IFI16 and cGAS cooperate to sense viral DNA in HSV-infected cells. • IFI16 plays a role in both innate sensing of HSV DNA and in restricting its expression.

  8. Assessment of HTLV-I proviral load, HIV viral load and CD4 T cell count in infected subjects; with an emphasis on viral replication in co-infection

    Directory of Open Access Journals (Sweden)

    Hossein Rahimi

    2014-01-01

    The mean viral load of HIV infected subjects and HTLV-I infected individuals were 134626.07±60031.07 copies/ml and 373.6±143.3 copies/104 cells, respectively. The mean HIV viral load in co-infected group was 158947±78203.59 copies/ml which is higher than HIV infected group. The mean proviral load of HTLV-I in co-infected group was 222.33±82.56 copies/ml which is lower than HTLV-I infected group (P

  9. Sero - Prevalence of Viral Transfusion-transmissible Infections amongst voluntary Blood donors

    Directory of Open Access Journals (Sweden)

    Rashida Elrashid Mohamed Ali

    2016-02-01

    Full Text Available This study aimed to determine the Sero-prevalence of viral transfusion-transmissible Infectious diseases among blood donors, namely immunodeficiency virus, hepatitis B and C transmissible infections (TTIs like HBV, HCV. HIV (Human immune viruses.. sero-prevalence of viral transmissible infections. The donated blood for specific antibodies for infections agents. Can largely reduce the risk of TTIs, virus among blood donors. The study was carried out in the blood bank at Khartoum Teaching Hospital, centre, Sudan. Screening of blood samples for hepatitis B surface Antigen (HBsAg, Human immunodeficiency virus (HIV and hepatitis C virus (HCV Antibodies were done using (ELISA enzyme link immunoassay. The study included (1184 voluntary Blood donors, all were males. The overall prevalence of viral transfusion transmissible Infections were (11.84%. The sero-prevalence for antibody against HIV (6 and hepatitis C Virus was positive in 8 (0.06 and (0.08% donors respectively while HBsAg was detected in 98 (9.8% donors.  situation that need for strict criteria for selection of blood donors and also methods of laboratory assays. Services are high in Sudan due to the endemicity of infections like malaria, nutritional problem and obstetrical emergencies associated with blood loss. Little is known about the level of these infections in Sudan so; this study was conducted to investigate the sero-prevalence of transfusion transmissible viral infectious diseases in particular human B and hepatitis Immunodeficiency, hepatitis C viruses. The mode of transmission for HIV, HBV and HCV is the same and includes unsafe Sexual sharp materials Contact, using contaminated with body fluid, mother to Child and transfusion of blood and blood Products.

  10. Etiology, seasonality, and clinical characterization of viral respiratory infections among hospitalized children in Beirut, Lebanon.

    Science.gov (United States)

    Finianos, Mayda; Issa, Randi; Curran, Martin D; Afif, Claude; Rajab, Maryam; Irani, Jihad; Hakimeh, Noha; Naous, Amal; Hajj, Marie-Joelle; Hajj, Pierre; El Jisr, Tamima; El Chaar, Mira

    2016-11-01

    Acute respiratory tract viral infections occur worldwide and are one of the major global burdens of diseases in children. The aim of this study was to determine the viral etiology of respiratory infections in hospitalized children, to understand the viral seasonality in a major Lebanese hospital, and to correlate disease severity and the presence of virus. Over a 1-year period, nasal and throat swabs were collected from 236 pediatric patients, aged 16-year old or less and hospitalized for acute respiratory illness. Samples collected were tested for the presence of 17 respiratory viruses using multiplex real-time RT-PCR. Pathogens were identified in 165 children (70%) and were frequently observed during fall and winter seasons. Co-infection was found in 37% of positive samples. The most frequently detected pathogens were human Rhinovirus (hRV, 23%), Respiratory Syncytial Virus (RSV, 19%), human Bocavirus (hBov, 15%), human Metapneumovirus (hMPV, 10%), and human Adenovirus (hAdV, 10%). A total of 48% of children were diagnosed with bronchiolitis and 25% with pneumonia. While bronchiolitis was often caused by RSV single virus infection and hAdV/hBoV coinfection, pneumonia was significantly associated with hBoV and HP1V1 infections. No significant correlation was observed between a single viral etiology infection and a specific clinical symptom. This study provides relevant facts on the circulatory pattern of respiratory viruses in Lebanon and the importance of using PCR as a useful tool for virus detection. Early diagnosis at the initial time of hospitalization may reduce the spread of the viruses in pediatric units. J. Med. Virol. 88:1874-1881, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. IL-10: A Multifunctional Cytokine in Viral Infections

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    José M. Rojas

    2017-01-01

    Full Text Available The anti-inflammatory master regulator IL-10 is critical to protect the host from tissue damage during acute phases of immune responses. This regulatory mechanism, central to T cell homeostasis, can be hijacked by viruses to evade immunity. IL-10 can be produced by virtually all immune cells, and it can also modulate the function of these cells. Understanding the effects of this multifunctional cytokine is therefore a complex task. In the present review we discuss the factors driving IL-10 production and the cellular sources of the cytokine during antiviral immune responses. We particularly focus on the IL-10 regulatory mechanisms that impact antiviral immune responses and how viruses can use this central regulatory pathway to evade immunity and establish chronic/latent infections.

  12. Achalasia and viral infection: new insights from veterinary medicine.

    Science.gov (United States)

    Ganem, Don; Kistler, Amy; DeRisi, Joseph

    2010-05-26

    Achalasia is a serious disorder in which the movement of food and liquids through the esophagus is impaired. It is currently thought to be caused by an inflammatory process that destroys neurons in myenteric ganglia, which affect peristalsis in the esophagus. The factor(s) that precipitate this inflammatory process are unknown; possibilities include environmental agents (such as microbes or toxins) and/or cell-mediated autoimmune reactivity. Recently, infection with a newly described bornavirus has been strongly linked to a disease of exotic birds that displays many striking similarities to achalasia. These findings demonstrate that viruses can induce achalasia-like pathophysiology and have renewed interest in the search for infectious agents in this enigmatic human disease.

  13. Rota Viral Infection: A Significant Disease Burden to Libya.

    Science.gov (United States)

    Alkoshi, Salem; Ernst, Kacey; Maimaiti, Namaitijiang; Dahlui, Maznah

    2014-10-01

    Rotavirus is a common infection causing 450,000 deaths annually primarily in children 5 years and below. Despite the high burden of disease, little is known about the epidemiology of rotavirus in Libya. The aim of this study was to estimate the rotavirus disease burden among Libyan children. A cross-sectional study was carried out prospectively among children 5 years old and below between August 2012 and April 2013. Stool samples of children with diarrhea attending the outpatient department or admitted to the pediatric wards, at three public hospitals within the northwestern region of Libya were tested for rotavirus. The seasonality, symptomology demographics and outcomes of rotavirus cases were determined and compared to other diarrhea illnesses. An estimated incidence rate per 100,000 children aged 5 years and below was determined. A total of 545 children with diarrhea were identified for participation. Results of rotavirus immunoassays determined 57% of cases were caused by rotavirus. Inpatients were more likely to be rotavirus positive than outpatients (58% vs. 53%, P<0.05), Most rotavirus positive cases (86%) were found among children below 2 years of age. Rotaviral cases peaked in the winter, constituting 76% of diarrheal illness in February and very few rotavirus cases in the summer months. The incidence rate of rotavirus diarrhea was estimated at 640/100,000 children aged 5 years and below. Rotavirus infection poses a significant disease burden in Libya. Preventive measures such as proper hygiene should be emphasized. Introduction of vaccination against rotavirus into the national immunization program should be examined, as it would likely be a cost-effective investment.

  14. Hepatitis A viral load in relation to severity of the infection.

    Science.gov (United States)

    Fujiwara, Keiichi; Kojima, Hiroshige; Yasui, Shin; Okitsu, Koichiro; Yonemitsu, Yutaka; Omata, Masao; Yokosuka, Osamu

    2011-02-01

    A correlation between hepatitis A virus (HAV) genomes and the clinical severity of hepatitis A has not been established. The viral load in sera of hepatitis A patients was examined to determine the possible association between hepatitis A severity and HAV replication. One hundred sixty-four serum samples from 91 Japanese patients with sporadic hepatitis A, comprising 11 patients with fulminant hepatitis, 10 with severe acute hepatitis, and 70 with self-limited acute hepatitis, were tested for HAV RNA. The sera included 83 serial samples from 20 patients. Viral load was measured by real-time RT-PCR. The detection rates of HAV RNA from fulminant, severe acute, and acute hepatitis were 10/11 (91%), 10/10 (100%), and 55/70 (79%), respectively. Mean values of HAV RNA at admission were 3.48 ± 1.30 logcopies/ml in fulminant, 4.19 ± 1.03 in severe acute, and 2.65 ± 1.64 in acute hepatitis. Patients with severe infection such as fulminant hepatitis and severe acute hepatitis had higher initial viral load than patients with less severe infection (P hepatitis after clinical onset (P = 0.19). HAV RNA was detectable quantitatively in the majority of the sera of hepatitis A cases during the early convalescent phase by real-time PCR. Higher initial viral replication was found in severely infected patients. An excessive host immune response might follow, reducing the viral load rapidly as a result of the destruction of large numbers of HAV-infected hepatocytes, and in turn severe disease might be induced.

  15. Evolution of hepatitis C viral quasispecies and hepatic injury in perinatally infected children followed prospectively.

    Science.gov (United States)

    Farci, Patrizia; Quinti, Isabella; Farci, Stefania; Alter, Harvey J; Strazzera, Rita; Palomba, Elvia; Coiana, Alessandra; Cao, Daniele; Casadei, Anna Maria; Ledda, Ritarella; Iorio, Raffaele; Vegnente, Angela; Diaz, Giacomo; Tovo, Pier-Angelo

    2006-05-30

    Perinatal infection with hepatitis C virus (HCV) is characterized by a wide range of alanine aminotransferase (ALT) levels. The mechanisms responsible for this variability are unknown. We examined whether the evolution of the HCV quasispecies was associated with different ALT profiles in perinatally infected children. Sequences within HCV envelope 1 and 2 genes, inclusive of the hypervariable region 1, the viral load, and the nascent humoral immunity were analyzed in serial serum samples from 12 perinatally infected children prospectively followed for a median of 53 months. These patients were selected to represent two different ALT patterns during the first year of life: 6 had high levels (maximum values ranging from 4.2 to 30 times the normal upper limit), and 6 had normal or slightly elevated levels (evolution were identified according to the ALT profiles. Biochemical evidence of hepatic injury was invariably associated with a mono- or oligoclonal viral population, whereas mild or no liver damage correlated with the early emergence of a heterogeneous viral quasispecies. Consistent with selective immune pressure, amino acid changes occurred almost exclusively within the hypervariable region 1 and were temporally associated with antibody seroconversion; at this time, the difference in genetic diversity between the two groups was highly significant (P = 0.002). The two patterns of viral evolution persisted over time and did not correlate with viral load or genotype. Our study demonstrates that, in perinatally infected children, the evolution of HCV quasispecies correlates with hepatic injury. The sequences reported in this paper have been deposited in the GenBank database (accession nos. DQ 504441-DQ 507112).

  16. A comparative review of HLA associations with hepatitis B and C viral infections across global populations

    Institute of Scientific and Technical Information of China (English)

    Rashmi Singh; Rashmi Kaul; Anil Kaul; Khalid Khan

    2007-01-01

    Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance ofchronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific

  17. ChemR23 dampens lung inflammation and enhances anti-viral immunity in a mouse model of acute viral pneumonia.

    Directory of Open Access Journals (Sweden)

    Benjamin Bondue

    2011-11-01

    Full Text Available Viral diseases of the respiratory tract, which include influenza pandemic, children acute bronchiolitis, and viral pneumonia of the elderly, represent major health problems. Plasmacytoid dendritic cells play an important role in anti-viral immunity, and these cells were recently shown to express ChemR23, the receptor for the chemoattractant protein chemerin, which is expressed by epithelial cells in the lung. Our aim was to determine the role played by the chemerin/ChemR23 system in the physiopathology of viral pneumonia, using the pneumonia virus of mice (PVM as a model. Wild-type and ChemR23 knock-out mice were infected by PVM and followed for functional and inflammatory parameters. ChemR23(-/- mice displayed higher mortality/morbidity, alteration of lung function, delayed viral clearance and increased neutrophilic infiltration. We demonstrated in these mice a lower recruitment of plasmacytoid dendritic cells and a reduction in type I interferon production. The role of plasmacytoid dendritic cells was further addressed by performing depletion and adoptive transfer experiments as well as by the generation of chimeric mice, demonstrating two opposite effects of the chemerin/ChemR23 system. First, the ChemR23-dependent recruitment of plasmacytoid dendritic cells contributes to adaptive immune responses and viral clearance, but also enhances the inflammatory response. Second, increased morbidity/mortality in ChemR23(-/- mice is not due to defective plasmacytoid dendritic cells recruitment, but rather to the loss of an anti-inflammatory pathway involving ChemR23 expressed by non-leukocytic cells. The chemerin/ChemR23 system plays important roles in the physiopathology of viral pneumonia, and might therefore be considered as a therapeutic target for anti-viral and anti-inflammatory therapies.

  18. ChemR23 dampens lung inflammation and enhances anti-viral immunity in a mouse model of acute viral pneumonia.

    Science.gov (United States)

    Bondue, Benjamin; Vosters, Olivier; de Nadai, Patricia; Glineur, Stéphanie; De Henau, Olivier; Luangsay, Souphalone; Van Gool, Frédéric; Communi, David; De Vuyst, Paul; Desmecht, Daniel; Parmentier, Marc

    2011-11-01

    Viral diseases of the respiratory tract, which include influenza pandemic, children acute bronchiolitis, and viral pneumonia of the elderly, represent major health problems. Plasmacytoid dendritic cells play an important role in anti-viral immunity, and these cells were recently shown to express ChemR23, the receptor for the chemoattractant protein chemerin, which is expressed by epithelial cells in the lung. Our aim was to determine the role played by the chemerin/ChemR23 system in the physiopathology of viral pneumonia, using the pneumonia virus of mice (PVM) as a model. Wild-type and ChemR23 knock-out mice were infected by PVM and followed for functional and inflammatory parameters. ChemR23(-/-) mice displayed higher mortality/morbidity, alteration of lung function, delayed viral clearance and increased neutrophilic infiltration. We demonstrated in these mice a lower recruitment of plasmacytoid dendritic cells and a reduction in type I interferon production. The role of plasmacytoid dendritic cells was further addressed by performing depletion and adoptive transfer experiments as well as by the generation of chimeric mice, demonstrating two opposite effects of the chemerin/ChemR23 system. First, the ChemR23-dependent recruitment of plasmacytoid dendritic cells contributes to adaptive immune responses and viral clearance, but also enhances the inflammatory response. Second, increased morbidity/mortality in ChemR23(-/-) mice is not due to defective plasmacytoid dendritic cells recruitment, but rather to the loss of an anti-inflammatory pathway involving ChemR23 expressed by non-leukocytic cells. The chemerin/ChemR23 system plays important roles in the physiopathology of viral pneumonia, and might therefore be considered as a therapeutic target for anti-viral and anti-inflammatory therapies.

  19. Persistent fetal infection with bovine viral diarrhea virus differentially affects maternal blood cell signal transduction pathways.

    Science.gov (United States)

    Smirnova, Natalia P; Ptitsyn, Andrey A; Austin, Kathleen J; Bielefeldt-Ohmann, Helle; Van Campen, Hana; Han, Hyungchul; van Olphen, Alberto L; Hansen, Thomas R

    2009-02-02

    The consequences of viral infection during pregnancy include impact on fetal and maternal immune responses and on fetal development. Transplacental infection in cattle with noncytopathic bovine viral diarrhea virus (ncpBVDV) during early gestation results in persistently infected (PI) fetuses with life-long viremia and susceptibility to infections. Infection of the fetus during the third trimester or after birth leads to a transient infection cleared by a competent immune system. We hypothesized that ncpBVDV infection and presence of an infected fetus would alter immune response and lead to downregulation of proinflammatory processes in pregnant dams. Naïve pregnant heifers were challenged with ncpBVDV2 on day 75 (PI fetus) and day 175 [transiently infected (TI) fetus] or kept uninfected (healthy control fetus). Maternal blood samples were collected up to day 190 of gestation. Genome-wide microarray analysis of gene expression in maternal peripheral white blood cells, performed on days 160 and 190 of gestation, revealed multiple signal transduction pathways affected by ncpBVDV infection. Acute infection and presence of a TI fetus caused upregulation of the type I interferon (IFN) pathway genes, including dsRNA sensors and IFN-stimulated genes. The presence of a PI fetus caused prolonged downregulation of chemokine receptor 4 (CXCR4) and T cell receptor (TCR) signaling in maternal blood cells. We conclude that: 1) infection with ncpBVDV induces a vigorous type I IFN response, and 2) presence of a PI fetus causes downregulation of important signaling pathways in the blood of the dam, which could have deleterious consequences on fetal development and the immune response.

  20. The importance of viral blips and duration of therapy initiated in primary infection in maintaining viral control after stopping cART

    OpenAIRE

    2014-01-01

    Introduction: After achieving undetectable HIV-RNA on cART, on cessation, HIV-RNA rebounds to pre-treatment values for the majority due to the presence of an inaccessible viral reservoir. There is some evidence that cART during primary HIV infection (PHI) limits the reservoir size, optimizing the chance of maintaining viral control off cART. Data are required to predict possible viral controllers for treatment interruption following cART. This analysis aims to investigate the effect of cART d...

  1. Modeling the within-host dynamics of cholera: bacterial-viral interaction.

    Science.gov (United States)

    Wang, Xueying; Wang, Jin

    2016-12-22

    Novel deterministic and stochastic models are proposed in this paper for the within-host dynamics of cholera, with a focus on the bacterial-viral interaction. The deterministic model is a system of differential equations describing the interaction among the two types of vibrios and the viruses. The stochastic model is a system of Markov jump processes that is derived based on the dynamics of the deterministic model. The multitype branching process approximation is applied to estimate the extinction probability of bacteria and viruses within a human host during the early stage of the bacterial-viral infection. Accordingly, a closed-form expression is derived for the disease extinction probability, and analytic estimates are validated with numerical simulations. The local and global dynamics of the bacterial-viral interaction are analysed using the deterministic model, and the result indicates that there is a sharp disease threshold characterized by the basic reproduction number [Formula: see text]: if [Formula: see text], vibrios ingested from the environment into human body will not cause cholera infection; if [Formula: see text], vibrios will grow with increased toxicity and persist within the host, leading to human cholera. In contrast, the stochastic model indicates, more realistically, that there is always a positive probability of disease extinction within the human host.

  2. In-depth characterization of viral isolates from plasma and cells compared with plasma circulating quasispecies in early HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Judith Dalmau

    Full Text Available BACKGROUND: The use of in vitro models to unravel the phenotypic characteristics of circulating viral variants is key to understanding HIV-1 pathogenesis but limited by the availability of primary viral isolates from biological samples. However, overall in vivo genetic variability of HIV-1 within a subject may not be reflected in the viable viral population obtained after isolation. Although several studies have tried to determine whether viral populations expanded in vitro are representative of in vivo findings, the answer remains unclear due to the reduced number of clonal sequences analyzed or samples compared. In order to overcome previous experimental limitations, here we applied Deep Pyrosequencing (DPS technology in combination with phenotypic experiments to analyze and compare with unprecedented detail the composition of viral isolates and in vivo quasispecies. METHODOLOGY/PRINCIPAL FINDINGS: We amplified by DPS HIV-1 genomic regions covering gag, protease, integrase and env-V3 to characterize paired isolates from plasma and peripheral blood mononuclear cells and compare them with total plasma viral RNA in four recently HIV-1 infected subjects. Our study demonstrated the presence of unique haplotypes scattered between sample types with conservation of major variants. In addition, no differences in intra- and inter-population encoded protein variability were found between the different types of isolates or when these were compared to plasma viral RNA within subjects. Additionally, in vitro experiments demonstrated phenotypic similarities in terms of replicative capacity and co-receptor usage between viral isolates and plasma viral RNA. CONCLUSION: This study is the first in-depth comparison and characterization of viral isolates from different sources and plasma circulating quasispecies using DPS in recently HIV-1 infected subjects. Our data supports the use of primary isolates regardless of their plasma or cellular origin to define

  3. Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia.

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    Kainulainen, Leena; Vuorinen, Tytti; Rantakokko-Jalava, Kaisu; Osterback, Riikka; Ruuskanen, Olli

    2010-07-01

    The occurrence of respiratory tract viral infections in patients with primary hypogammaglobulinemia has not been studied. We conducted a prospective 12-month follow-up study of respiratory tract infections in 12 adult patients with primary hypogammaglobulinemia. Nasal swab samples and induced sputum samples were taken at the onset of acute respiratory tract infection and every 3 months thereafter. Samples were tested for bacteria and viruses. PCR tests were performed for 15 respiratory tract viruses. In case the results for rhinovirus were positive, follow-up nasal swab samples were taken every 2 weeks until rhinoviral PCR results became negative. Patients completed symptom diaries, which were collected every month. The spouses of the patients served as healthy control subjects. During the 12-month period, the 12 patients had 65 episodes of acute respiratory tract infections, and the 11 spouses had 12 acute episodes (P < .001). Respiratory tract viruses were found in sputum in 54% of the infections. Rhinovirus was the most common virus. In more than half of our patients, rhinoviral PCR results stayed positive for more than 2 months. The most long-acting persistence with the same rhinovirus was 4 months. Despite adequate immunoglobulin replacement therapy, patients with primary hypogammaglobulinemia have increased susceptibility to respiratory tract viral infections. Rhinoviral infections are frequent and prolonged. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  4. Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus.

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    Hansen, Thomas R; Smirnova, Natalia P; Webb, Brett T; Bielefeldt-Ohmann, Helle; Sacco, Randy E; Van Campen, Hana

    2015-06-01

    Infection of pregnant cows with noncytopathic (ncp) bovine viral diarrhea virus (BVDV) induces rapid innate and adaptive immune responses, resulting in clearance of the virus in less than 3 weeks. Seven to 14 days after inoculation of the cow, ncpBVDV crosses the placenta and induces a fetal viremia. Establishment of persistent infection with ncpBVDV in the fetus has been attributed to the inability to mount an immune response before 90-150 days of gestational age. The result is 'immune tolerance', persistent viral replication and shedding of ncpBVDV. In contrast, we describe the chronic upregulation of fetal Type I interferon (IFN) pathway genes and the induction of IFN-γ pathways in fetuses of cows infected on day 75 of gestation. Persistently infected (PI) fetal IFN-γ concentrations also increased at day 97 at the peak of fetal viremia and IFN-γ mRNA was significantly elevated in fetal thymus, liver and spleen 14-22 days post maternal inoculation. PI fetuses respond to ncpBVDV infection through induction of Type I IFN and IFN-γ activated genes leading to a reduction in ncpBVDV titer. We hypothesize that fetal infection with BVDV persists because of impaired induction of IFN-γ in the face of activated Type I IFN responses. Clarification of the mechanisms involved in the IFN-associated pathways during BVDV fetal infection may lead to better detection methods, antiviral compounds and selection of genetically resistant breeding animals.

  5. Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle.

    Science.gov (United States)

    Li, Qisheng; Zhang, Yong-Yuan; Chiu, Stephan; Hu, Zongyi; Lan, Keng-Hsin; Cha, Helen; Sodroski, Catherine; Zhang, Fang; Hsu, Ching-Sheng; Thomas, Emmanuel; Liang, T Jake

    2014-05-01

    Recent functional genomics studies including genome-wide small interfering RNA (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc) siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp), single-cycle infectious particles (HCVsc), subgenomic replicons, and HCV cell culture systems (HCVcc), we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase α, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE), a proviral factor, and N-Myc down regulated Gene 1 (NDRG1), an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study of HCV host

  6. Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle.

    Directory of Open Access Journals (Sweden)

    Qisheng Li

    2014-05-01

    Full Text Available Recent functional genomics studies including genome-wide small interfering RNA (siRNA screens demonstrated that hepatitis C virus (HCV exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp, single-cycle infectious particles (HCVsc, subgenomic replicons, and HCV cell culture systems (HCVcc, we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase α, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE, a proviral factor, and N-Myc down regulated Gene 1 (NDRG1, an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study

  7. Host immune responses to a viral immune modulating protein: immunogenicity of viral interleukin-10 in rhesus cytomegalovirus-infected rhesus macaques.

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    Meghan K Eberhardt

    Full Text Available BACKGROUND: Considerable evidence has accumulated that multiple viruses, bacteria, and protozoa manipulate interleukin-10 (IL-10-mediated signaling through the IL-10 receptor (IL-10R in ways that could enable establishment of a persistent microbial infection. This suggests that inhibition of pathogen targeting of IL-10/IL-10R signaling could prevent microbial persistence. Human cytomegalovirus (HCMV and rhesus cytomegalovirus (RhCMV express a viral interleukin-10 (cmvIL-10 and rhcmvIL-10, respectively with comparable immune modulating properties in vitro to that of their host's cellular IL-10 (cIL-10. A prior study noted that rhcmvIL-10 alters innate and adaptive immunity to RhCMV in vivo, consistent with a central role for rhcmvIL-10 during acute virus-host interactions. Since cmvIL-10 and rhcmvIL-10 are extremely divergent from the cIL-10 of their respective hosts, vaccine-mediated neutralization of their function could inhibit establishment of viral persistence without inhibition of cIL-10. METHODS AND FINDINGS: As a prelude to evaluating cmvIL-10-based vaccines in humans, the rhesus macaque model of HCMV was used to interrogate peripheral and mucosal immune responses to rhcmvIL-10 in RhCMV-infected animals. ELISA were used to detect rhcmvIL-10-binding antibodies in plasma and saliva, and an IL-12-based bioassay was used to quantify plasma antibodies that neutralized rhcmvIL-10 function. rhcmvIL-10 is highly immunogenic during RhCMV infection, stimulating high avidity rhcmvIL-10-binding antibodies in the plasma of all infected animals. Most infected animals also exhibited plasma antibodies that partially neutralized rhcmvIL-10 function but did not cross-neutralize the function of rhesus cIL-10. Notably, minimally detectable rhcmvIL-10-binding antibodies were detected in saliva. CONCLUSION: This study demonstrates that rhcmvIL-10, as a surrogate for cmvIL-10, is a viable vaccine candidate because (1 it is highly immunogenic during natural Rh

  8. Inhibition of Influenza A Virus Infection by Fucoidan Targeting Viral Neuraminidase and Cellular EGFR Pathway

    Science.gov (United States)

    Wang, Wei; Wu, Jiandong; Zhang, Xiaoshuang; Hao, Cui; Zhao, Xiaoliang; Jiao, Guangling; Shan, Xindi; Tai, Wenjing; Yu, Guangli

    2017-01-01

    Development of novel anti-influenza A virus (IAV) drugs with high efficiency and low toxicity is critical for preparedness against influenza outbreaks. Herein, we investigated the anti-IAV activities and mechanisms of fucoidan in vitro and in vivo. The results showed that a fucoidan KW derived from brown algae Kjellmaniella crassifolia effectively blocked IAV infection in vitro with low toxicity. KW possessed broad anti-IAV spectrum and low tendency of induction of viral resistance, superior to the anti-IAV drug amantadine. KW was capable of inactivating virus particles before infection and blocked some stages after adsorption. KW could bind to viral neuraminidase (NA) and inhibit the activity of NA to block the release of IAV. KW also interfered with the activation of EGFR, PKCα, NF-κB, and Akt, and inhibited both IAV endocytosis and EGFR internalization in IAV-infected cells, suggesting that KW may also inhibit cellular EGFR pathway. Moreover, intranasal administration of KW markedly improved survival and decreased viral titers in IAV-infected mice. Therefore, fucoidan KW has the potential to be developed into a novel nasal drop or spray for prevention and treatment of influenza in the future. PMID:28094330

  9. Viral latency in blood and saliva of simian foamy virus-infected humans.

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    Rejane Rua

    Full Text Available Simian foamy viruses (SFV are widespread retroviruses among non-human primates (NHP. SFV actively replicate in the oral cavity and can be transmitted to humans through NHP bites, giving rise to a persistent infection. We aimed at studying the natural history of SFV infection in human. We have analyzed viral load and gene expression in 14 hunters from Cameroon previously shown to be infected with a gorilla SFV strain. Viral DNA could be detected by quantitative polymerase chain reaction (q-PCR targeting the pol-in region, in most samples of peripheral blood mononuclear cells (PBMCs (7.1 ± 6.0 SFV DNA copies/105 PBMCs and saliva (2.4 ± 4.3 SFV DNA copies/105 cells derived from the hunters. However, quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR revealed the absence of SFV viral gene expression in both PBMCs and saliva, suggesting that SFV was latent in the human samples. Our study demonstrates that a latent infection can occur in humans and persist for years, both in PBMCs and saliva. Such a scenario may contribute to the putative lack of secondary human-to-human transmissions of SFV.

  10. Identification of bovine viral diarrhea virus infection in Saanen goats in the Republic of Korea.

    Science.gov (United States)

    Han, Yu-Jung; Chae, Jeong-Byoung; Chae, Joon-Seok; Yu, Do-Hyeon; Park, Jinho; Park, Bae-Keun; Kim, Hyeon-Cheol; Yoo, Jae-Gyu; Choi, Kyoung-Seong

    2016-06-01

    Bovine viral diarrhea virus (BVDV) is one of the most important viral pathogens of livestock and causes substantial economic losses to the livestock industry worldwide. BVDV is not necessarily species specific and is known to infect domesticated and wild ruminants. In the present study, BVDV infection was identified in two Saanen goats from one farm, and two different viral subtypes were found, BVDV-1a and BVDV-2a. Each isolate was closely related to cattle isolates identified in the Republic of Korea. The two sequences obtained in this study were not consistent with border disease virus (BDV). The incidence of BVDV in this farm apparently occurred in the absence of contact with cattle and may be associated with grazing. This study demonstrates that BVDV infection may be possible to transmit among goats without exposure to cattle. Therefore, this result indicates that Saanen goats may act as natural reservoirs for BVDV. This is the first report of BVDV-1a infection in a Saanen goat.

  11. High-programmed death-1 levels on hepatitis C virus-specific T cells during acute infection are associated with viral persistence and require preservation of cognate antigen during chronic infection.

    Science.gov (United States)

    Rutebemberwa, Alleluiah; Ray, Stuart C; Astemborski, Jacquie; Levine, Jordana; Liu, Lin; Dowd, Kimberly A; Clute, Shalyn; Wang, Changyu; Korman, Alan; Sette, Alessandro; Sidney, John; Pardoll, Drew M; Cox, Andrea L

    2008-12-15

    Hepatitis C virus (HCV) is an important human pathogen that represents a model for chronic infection given that the majority of infected individuals fail to clear the infection despite generation of virus-specific T cell responses during the period of acute infection. Although viral sequence evolution at targeted MHC class I-restricted epitopes represents one mechanism for immune escape in HCV, many targeted epitopes remain intact under circumstances of viral persistence. To explore alternative mechanisms of HCV immune evasion, we analyzed patterns of expression of a major inhibitory receptor on T cells, programmed death-1 (PD-1), from the time of initial infection and correlated these with HCV RNA levels, outcome of infection, and sequence escape within the targeted epitope. We show that the level of PD-1 expression in early HCV infection is significantly higher on HCV-specific T cells from subjects who progress to chronic HCV infection than from those who clear infection. This correlation is independent of HCV RNA levels, compatible with the notion that high PD-1 expression on HCV-specific CD8 T cells during acute infection inhibits viral clearance. Viral escape during persistent infection is associated with reduction in PD-1 levels on the surface of HCV-specific T cells, supporting the necessity of ongoing antigenic stimulation of T cells for maintenance of PD-1 expression. These results support the idea that PD-1 expression on T cells specific for nonescaped epitopes contributes to viral persistence and suggest that PD-1 blockade may alter the outcome of HCV infection.

  12. Early postnatal respiratory viral infection alters hippocampal neurogenesis, cell fate, and neuron morphology in the neonatal piglet.

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    Conrad, Matthew S; Harasim, Samantha; Rhodes, Justin S; Van Alstine, William G; Johnson, Rodney W

    2015-02-01

    Respiratory viral infections are common during the neonatal period in humans, but little is known about how early-life infection impacts brain development. The current study used a neonatal piglet model as piglets have a gyrencephalic brain with growth and development similar to human infants. Piglets were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) to evaluate how chronic neuroinflammation affects hippocampal neurogenesis and neuron morphology. Piglets in the neurogenesis study received one bromodeoxyuridine injection on postnatal day (PD) 7 and then were inoculated with PRRSV. Piglets were sacrificed at PD 28 and the number of BrdU+ cells and cell fate were quantified in the dentate gyrus. PRRSV piglets showed a 24% reduction in the number of newly divided cells forming neurons. Approximately 15% of newly divided cells formed microglia, but this was not affected by sex or PRRSV. Additionally, there was a sexual dimorphism of new cell survival in the dentate gyrus where males had more cells than females, and PRRSV infection caused a decreased survival in males only. Golgi impregnation was used to characterize dentate granule cell morphology. Sholl analysis revealed that PRRSV caused a change in inner granule cell morphology where the first branch point was extended further from the cell body. Males had more complex dendritic arbors than females in the outer granule cell layer, but this was not affected by PRRSV. There were no changes to dendritic spine density or morphology distribution. These findings suggest that early-life viral infection can impact brain development.

  13. Viral infections stimulate the metabolism and shape prokaryotic assemblages in submarine mud volcanoes.

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    Corinaldesi, Cinzia; Dell'Anno, Antonio; Danovaro, Roberto

    2012-06-01

    Mud volcanoes are geological structures in the oceans that have key roles in the functioning of the global ecosystem. Information on the dynamics of benthic viruses and their interactions with prokaryotes in mud volcano ecosystems is still completely lacking. We investigated the impact of viral infection on the mortality and assemblage structure of benthic prokaryotes of five mud volcanoes in the Mediterranean Sea. Mud volcano sediments promote high rates of viral production (1.65-7.89 × 10(9) viruses g(-1) d(-1)), viral-induced prokaryotic mortality (VIPM) (33% cells killed per day) and heterotrophic prokaryotic production (3.0-8.3 μgC g(-1) d(-1)) when compared with sediments outside the mud volcano area. The viral shunt (that is, the microbial biomass converted into dissolved organic matter as a result of viral infection, and thus diverted away from higher trophic levels) provides 49 mgC m(-2) d(-1), thus fuelling the metabolism of uninfected prokaryotes and contributing to the total C budget. Bacteria are the dominant components of prokaryotic assemblages in surface sediments of mud volcanoes, whereas archaea dominate the subsurface sediment layers. Multivariate multiple regression analyses show that prokaryotic assemblage composition is not only dependant on the geochemical features and processes of mud volcano ecosystems but also on synergistic interactions between bottom-up (that is, trophic resources) and top-down (that is, VIPM) controlling factors. Overall, these findings highlight the significant role of the viral shunt in sustaining the metabolism of prokaryotes and shaping their assemblage structure in mud volcano sediments, and they provide new clues for our understanding of the functioning of cold-seep ecosystems.

  14. Novel microRNA-like viral small regulatory RNAs arising during human hepatitis A virus infection.

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    Shi, Jiandong; Sun, Jing; Wang, Bin; Wu, Meini; Zhang, Jing; Duan, Zhiqing; Wang, Haixuan; Hu, Ningzhu; Hu, Yunzhang

    2014-10-01

    MicroRNAs (miRNAs), including host miRNAs and viral miRNAs, play vital roles in regulating host-virus interactions. DNA viruses encode miRNAs that regulate the viral life cycle. However, it is generally believed that cytoplasmic RNA viruses do not encode miRNAs, owing to inaccessible cellular miRNA processing machinery. Here, we provide a comprehensive genome-wide analysis and identification of miRNAs that were derived from hepatitis A virus (HAV; Hu/China/H2/1982), which is a typical cytoplasmic RNA virus. Using deep-sequencing and in silico approaches, we identified 2 novel virally encoded miRNAs, named hav-miR-1-5p and hav-miR-2-5p. Both of the novel virally encoded miRNAs were clearly detected in infected cells. Analysis of Dicer enzyme silencing demonstrated that HAV-derived miRNA biogenesis is Dicer dependent. Furthermore, we confirmed that HAV mature miRNAs were generated from viral miRNA precursors (pre-miRNAs) in host cells. Notably, naturally derived HAV miRNAs were biologically and functionally active and induced post-transcriptional gene silencing (PTGS). Genomic location analysis revealed novel miRNAs located in the coding region of the viral genome. Overall, our results show that HAV naturally generates functional miRNA-like small regulatory RNAs during infection. This is the first report of miRNAs derived from the coding region of genomic RNA of a cytoplasmic RNA virus. These observations demonstrate that a cytoplasmic RNA virus can naturally generate functional miRNAs, as DNA viruses do. These findings also contribute to improved understanding of host-RNA virus interactions mediated by RNA virus-derived miRNAs.

  15. Identification of viral infections in the prostate and evaluation of their association with cancer

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    Calderon-Cardenas German

    2010-06-01

    Full Text Available Abstract Background Several viruses with known oncogenic potential infect prostate tissue, among these are the polyomaviruses BKV, JCV, and SV40; human papillomaviruses (HPVs, and human cytomegalovirus (HCMV infections. Recently, the Xenotropic Murine Leukemia Virus-related gammaretrovirus (XMRV was identified in prostate tissue with a high prevalence observed in prostate cancer (PC patients homozygous for the glutamine variant of the RNASEL protein (462Q/Q. Association studies with the R462Q allele and non-XMRV viruses have not been reported. We assessed associations between prostate cancer, prostate viral infections, and the RNASEL 462Q allele in Mexican cancer patients and controls. Methods 130 subjects (55 prostate cancer cases and 75 controls were enrolled in the study. DNA and RNA isolated from prostate tissues were screened for the presence of viral genomes. Genotyping of the RNASEL R462Q variant was performed by Taqman method. Results R/R, R/Q, and Q/Q frequencies for R462Q were 0.62, 0.38, and 0.0 for PC cases and 0.69, 0.24, and 0.07 for controls, respectively. HPV sequences were detected in 11 (20.0% cases and 4 (5.3% controls. XMRV and HCMV infections were detected in one and six control samples, respectively. The risk of PC was significantly increased (Odds Ratio = 3.98; 95% CI: 1.17-13.56, p = 0.027 by infection of the prostatic tissue with HPV. BKV, JCV, and SV40 sequences were not detected in any of the tissue samples examined. Conclusions We report a positive association between PC and HPV infection. The 462Q/Q RNASEL genotype was not represented in our PC cases; thus, its interaction with prostate viral infections and cancer could not be evaluated.

  16. Carbohydrate-Based Ice Recrystallization Inhibitors Increase Infectivity and Thermostability of Viral Vectors

    Science.gov (United States)

    Ghobadloo, Shahrokh M.; Balcerzak, Anna K.; Gargaun, Ana; Muharemagic, Darija; Mironov, Gleb G.; Capicciotti, Chantelle J.; Briard, Jennie G.; Ben, Robert N.; Berezovski, Maxim V.

    2014-07-01

    The inability of vaccines to retain sufficient thermostability has been an obstacle to global vaccination programs. To address this major limitation, we utilized carbohydrate-based ice recrystallization inhibitors (IRIs) to eliminate the cold chain and stabilize the potency of Vaccinia virus (VV), Vesicular Stomatitis virus (VSV) and Herpes virus-1 (HSV-1). The impact of these IRIs was tested on the potency of the viral vectors using a plaque forming unit assay following room temperature storage, cryopreservation with successive freeze-thaw cycles and lyophilization. Viral potency after storage with all three conditions demonstrated that N-octyl-gluconamide (NOGlc) recovered the infectivity of shelf stored VV, 5.6 Log10 PFU mL-1 during 40 days, and HSV-1, 2.7 Log10 PFU mL-1 during 9 days. Carbon-linked antifreeze glycoprotein analogue ornithine-glycine-glycine-galactose (OGG-Gal) increases the recovery of VV and VSV more than 1 Log10 PFU mL-1 after 10 freeze-thaw cycles. In VSV, cryostorage with OGG-Gal maintains high infectivity and reduces temperature-induced aggregation of viral particles by 2 times that of the control. In total, OGG-Gal and NOGlc preserve virus potency during cryostorage. Remarkably, NOGlc has potential to eliminate the cold chain and permit room temperature storage of viral vectors.

  17. Carbohydrate-based ice recrystallization inhibitors increase infectivity and thermostability of viral vectors.

    Science.gov (United States)

    Ghobadloo, Shahrokh M; Balcerzak, Anna K; Gargaun, Ana; Muharemagic, Darija; Mironov, Gleb G; Capicciotti, Chantelle J; Briard, Jennie G; Ben, Robert N; Berezovski, Maxim V

    2014-07-31

    The inability of vaccines to retain sufficient thermostability has been an obstacle to global vaccination programs. To address this major limitation, we utilized carbohydrate-based ice recrystallization inhibitors (IRIs) to eliminate the cold chain and stabilize the potency of Vaccinia virus (VV), Vesicular Stomatitis virus (VSV) and Herpes virus-1 (HSV-1). The impact of these IRIs was tested on the potency of the viral vectors using a plaque forming unit assay following room temperature storage, cryopreservation with successive freeze-thaw cycles and lyophilization. Viral potency after storage with all three conditions demonstrated that N-octyl-gluconamide (NOGlc) recovered the infectivity of shelf stored VV, 5.6 Log₁₀ PFU mL(-1) during 40 days, and HSV-1, 2.7 Log₁₀ PFU mL(-1) during 9 days. Carbon-linked antifreeze glycoprotein analogue ornithine-glycine-glycine-galactose (OGG-Gal) increases the recovery of VV and VSV more than 1 Log₁₀ PFU mL(-1) after 10 freeze-thaw cycles. In VSV, cryostorage with OGG-Gal maintains high infectivity and reduces temperature-induced aggregation of viral particles by 2 times that of the control. In total, OGG-Gal and NOGlc preserve virus potency during cryostorage. Remarkably, NOGlc has potential to eliminate the cold chain and permit room temperature storage of viral vectors.

  18. [Laboratory diagnosis of HIV infection, viral tropism and resistance to antiretrovirals].

    Science.gov (United States)

    García, Federico; Álvarez, Marta; Bernal, Carmen; Chueca, Natalia; Guillot, Vicente

    2011-04-01

    The accurate diagnosis of HIV infection demands that to consider a positive result, at least three assays with different antigenic base should be used, one of them, Western-Blot being mandatory for confirmation. Fourth generation ELISAs shorten the window phase to 13-15 days, as they now include p24 antigen detection. Proviral DNA or Viral RNA detection by molecular methods have proved useful for addressing complex situations in which serology was inconclusive. Viral load (HIV-RNA) is routinely used to follow-up HIV infected patients and is used for treatment initiation decisions. It is also used to monitor viral failure. When this happens, resistance tests are needed to guide treatment changes. Resistance is also used to assess the transmission of drug resistance to newly diagnosed patients. Finally, before using an anti-CCR5 drug, viral tropism needs to be determined. This can be done using genotypic tests, widely available in many HIV labs, or phenotypic tests, only available at certain sites.

  19. Efficacy and safety on tenofovire therapy in patients with hepatitis B viral infections resistent to lamivudin

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    Katanić N.

    2015-01-01

    Full Text Available Chronic viral hepatitis B (CHB still represents a significant world health problem despite obligatory and worldwide immunization against infections of viral hepatitis B. In some patients with chronic viral hepatitis B infections, in the natural course of the disease, progression towards cirhossis and hepatocellular carcinoma is primarily targeted by antiviral CHB therapy stopping further progression of the disease. Today on the market there exist two classes of pharmnaceutical drugs for treatment of CHB: a immunomodulatory therapy with conventional interferon alpha (INF and PEGylated interferon alpha-2a, b and oral antiviral therapy with nucleos( tide analogues. Lamivudine was for quite a period the only medicament available on our market for the treatment of HVB and in most of our patients led to the development of resistance. As of two years ago, a new oral analogue from the group of nucleotides is being registered in Serbia for market use: tenofovir disoproxil (TDF. In our work we have analysed 69 patients with chronic viral hepatitis B treated in the Clinic for Infectious and Tropical Diseases KCS Belgrade in the period between years 2012 and 2014. All patients involved in this reasearch were previously treated with LAM, and on subsequent development of resistance to LAM, TDF was used. TDF showed an excellent efficacy, a high resistance barrier and very few unwanted side effects over several years of treatment. Our experience with the use of this drug does not pertain to and acount for its long term use, in view of its brief availability on our market.

  20. Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis

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    Brody Steven L

    2010-06-01

    Full Text Available Abstract Background Viral bronchiolitis is the leading cause of hospitalization in young infants. It is associated with the development of childhood asthma and contributes to morbidity and mortality in the elderly. Currently no therapies effectively attenuate inflammation during the acute viral infection, or prevent the risk of post-viral asthma. We hypothesized that early treatment of a paramyxoviral bronchiolitis with azithromycin would attenuate acute and chronic airway inflammation. Methods Mice were inoculated with parainfluenza type 1, Sendai Virus (SeV, and treated daily with PBS or azithromycin for 7 days post-inoculation. On day 8 and 21 we assessed airway inflammation in lung tissue, and quantified immune cells and inflammatory mediators in bronchoalveolar lavage (BAL. Results Compared to treatment with PBS, azithromycin significantly attenuated post-viral weight loss. During the peak of acute inflammation (day 8, azithromycin decreased total leukocyte accumulation in the lung tissue and BAL, with the largest fold-reduction in BAL neutrophils. This decreased inflammation was independent of changes in viral load. Azithromycin significantly attenuated the concentration of BAL inflammatory mediators and enhanced resolution of chronic airway inflammation evident by decreased BAL inflammatory mediators on day 21. Conclusions In this mouse model of paramyxoviral bronchiolitis, azithromycin attenuated acute and chronic airway inflammation. These findings demonstrate anti-inflammatory effects of azithromycin that are not related to anti-viral activity. Our findings support the rationale for future prospective randomized clinical trials that will evaluate the effects of macrolides on acute viral bronchiolitis and their long-term consequences.

  1. The role of viral infection in inducing variability in virus-free progeny in tomato.

    Science.gov (United States)

    Marii, Liliana; Chiriac, Gheorghe

    2009-05-01

    The effect of virus-host interactions on subsequent generations is poorly understood. The evaluation of the effects of viral infection on inheritance of quantitative traits in the progeny of infected plants and elucidation of a possible relationship between chiasma frequency in the infected plants and variability of traits in the progeny were investigated. The current study involved genotypes of four intraspecific hybrids of tomato (Solanum lycopersicum L.), their parental forms and two additional cultivars. Used as infection were the tobacco mosaic virus (TMV) and potato virus X (PVX). The consequences of the effect of viral infection were evaluated based on chromosome pairing in diakinesis and/or by examining quantitative and qualitative traits in the progeny of the infected tomato plants. Tomato plants infected with TMV + PVX were found to differ in chiasma frequency per pollen mother cell or per bivalent. Deviations have been observed for genotypes of both F(1) hybrids and cultivars. At the same time, differences in mean values of the traits under study have only been found for progeny populations (F(2)-F(4)) derived from virus-infected F(1) hybrids, but not in the case of progeny of the infected cultivars. The rate of recombinants combining traits of both parents increased significantly (2.22-8.24 times) in progeny populations of hybrids infected with TMV + PVX. The above suggests that the observed effects could be the result of modification of recombination frequencies that can be manifested in heterozygous hybrids and make small contributions to variability in cases of 'homozygous' tomato genotypes (i.e. cultivars).

  2. The Role of Viral Infection in Inducing Variability in Virus-Free Progeny in Tomato

    Institute of Scientific and Technical Information of China (English)

    Liliana Marii; Gheorghe Chiriac

    2009-01-01

    The effect of virus-host interactions on subsequent generations is poorly understood. The evaluation of the effects of viral infection on inheritance of quantitative traits in the progeny of infected plants and elucidation of a possible relationship between chiasma frequency in the infected plants and variability of traits in the progeny were investigated. The current study involved genotypes of four intraspecific hybrids of tomato (Solanum lycopersicum L.), their parental forms and two additional cultivars. Used as infection were the tobacco mosaic virus (TMV) and potato virus X (PVX). The consequences of the effect of viral infection were evaluated based on chromosome pairing in diakinesis and/or by examining quantitative and qualitative traits in the progeny of the infected tomato plants. Tomato plants infected with TMV + PVX were found to differ in chiasma frequency per pollen mother cell or per bivalent. Deviations have been observed for genotypes of both F1 hybrids and cultivars. At the same time, differences in mean values of the traits under study have only been found for progeny populations (F2-F4) derived from virus-infected F1 hybrids, but not in the case of progeny of the infected cultivars. The rate of recombinants combining traits of both parents increased significantly (2.22-8.24 times) in progeny populations of hybrids infected with TMV + PVX. The above suggests that the observed effects could be the result of modification of recombination frequencies that can be manifested in heterozygous hybrids and make small contributions to variability in cases of 'homozygous' tomato genotypes (I.e. Cultivars).

  3. Antigen-loaded ER microsomes from APC induce potent immune responses against viral infection.

    Science.gov (United States)

    Sofra, Vassiliki; Mansour, Salah; Liu, Mengya; Gao, Bin; Primpidou, Elisavet; Wang, Ping; Li, Suling

    2009-01-01

    Although matured DC are capable of inducing effective primary and secondary immune responses in vivo, it is difficult to control the maturation and antigen loading in vitro. In this study, we show that ER-enriched microsomal membranes (microsomes) isolated from DC contain more peptide-receptive MHC I and II molecules than, and a similar level of costimulatory molecules to, their parental DC. After loading with defined antigenic peptides, the microsomes deliver antigenic peptide-MHC complexes (pMHC) to both CD4 and CD8 T cells effectively in vivo. The peptide-loaded microsomes accumulate in peripheral lymphoid organs and induce stronger immune responses than peptide-pulsed DC. The microsomal vaccines protect against acute viral infection. Our data demonstrate that peptide-MHC complexes armed microsomes from DC can be an important alternative to DC-based vaccines for protection from viral infection.

  4. Coherent Brightfield Microscopy Provides the Spatiotemporal Resolution To Study Early Stage Viral Infection in Live Cells.

    Science.gov (United States)

    Huang, Yi-Fan; Zhuo, Guan-Yu; Chou, Chun-Yu; Lin, Cheng-Hao; Chang, Wen; Hsieh, Chia-Lung

    2017-03-28

    Viral infection starts with a virus particle landing on a cell surface followed by penetration of the plasma membrane. Due to the difficulty of measuring the rapid motion of small-sized virus particles on the membrane, little is known about how a virus particle reaches an endocytic site after landing at a random location. Here, we use coherent brightfield (COBRI) microscopy to investigate early stage viral infection with ultrahigh spatiotemporal resolution. By detecting intrinsic scattered light via imaging-based interferometry, COBRI microscopy allows us to track the motion of a single vaccinia virus particle with nanometer spatial precision (speed scattering-based optical imaging may provide opportunities for resolving rapid virus-receptor interactions with nanometer clarity.

  5. Cell-mediated cytotoxicity in rainbow trout, Oncorhynchus mykiss, infected with viral haemorrhagic septicaemia virus

    DEFF Research Database (Denmark)

    Utke, K.; Bergmann, S.; Lorenzen, Niels

    2007-01-01

    Mammalian cytotoxic T cells as part of the adaptive immune system recognize virus-infected target cells by binding of their T-cell receptors (TCR) to classical MHC class I molecules loaded with viral peptides. Our previous studies have shown that the allele of the single dominant polymorphic...... level of the CD8 alpha gene which is a typical marker for mammalian cytotoxic T cells. Concurrently, the expression of the natural killer cell enhancement factor (NKEF)-like gene was enhanced as measured by real-time RT-PCR. Taken together, these results suggest that both innate and adaptive cell....... This is contradictory to the generally accepted rule that innate immune mechanisms represent the first line of defence after viral infections....

  6. Co-ordinating innate and adaptive immunity to viral infection: mobility is the key

    DEFF Research Database (Denmark)

    Wern, Jeanette Erbo; Thomsen, Allan Randrup

    2009-01-01

    The host counters a viral infection through a complex response made up of components belonging to both the innate and the adaptive immune system. In this report, we review the mechanisms underlying this response, how it is induced and how it is co-ordinated. As cell-cell communication represents...... in mounting an efficient host response and co-ordinating innate and adaptive immunity during a primary viral infection....... the very essence of immune system physiology, a key to a rapid, efficient and optimally regulated immune response is the ability of the involved cells to rapidly shift between a stationary and a mobile state, combined with stringent regulation of cell migration during the mobile state. Through the co...

  7. Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells

    Energy Technology Data Exchange (ETDEWEB)

    Iordanskiy, Sergey [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Van Duyne, Rachel [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Sampey, Gavin C; Woodson, Caitlin M; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Romerio, Fabio [Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Kashanchi, Fatah, E-mail: fkashanc@gmu.edu [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States)

    2015-11-15

    The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4{sup +} T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4{sup +} T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4{sup +} T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. - Highlights: • X-ray irradiation

  8. Interferon response following infection with genetically similar isolates of viral haemorrhagic septicaemia virus (VHSV) exhibiting contrasting virulence in rainbow trout.

    Science.gov (United States)

    Campbell, S; McBeath, A; Secombes, C; Snow, M; Collet, B

    2011-01-01

    Isolates of viral haemorrhagic septicaemia virus (VHSV) were identified which are genetically similar yet, based on their isolation history were considered likely to differ in virulence in juvenile rainbow trout. An experimental infection study was performed in order to verify this hypothesis and provide an experimental infectivity model with which to investigate the basis for susceptibility of rainbow trout to this commercially important virus. Significant differences in mortality were obtained following both intraperitoneal (IP) injection and immersion challenges with an early marine (DK-M.Rhabdo) and early rainbow trout VHSV isolate (DK-F1) respectively. Expression of Type I IFN, Mx1 (an IFN-inducible protein), and viral genes (encoding nucleo-, phospho-, matrix, glyco- and non-viron proteins) was studied in sequential tissue samples using real-time quantitative PCR (QPCR). Resulting data revealed a significant increase in IFN and Mx1 expression detected in fish challenged by IP injection with both isolates. Expression levels of these genes were directly related to the degree of viral replication as measured by the expression of VHSV RNAs. In immersion-challenged fish a significant increase in Mx1 was observed only when using the virulent isolate DK-F1; however no elevated host response was detectable in fish challenged with the marine isolate DK-M.Rhabdo. Quintessentially the inability to detect any virus in trout challenged with the marine isolate via immersion suggests the virus was incapable of establishing infection. The mechanisms for this appear to be more related to initial cellular entry and replication rather than due to the overcoming of initial infection via an elevated host innate immune response.

  9. A comprehensive collection of systems biology data characterizing the host response to viral infection

    OpenAIRE

    Aevermann, Brian D.; Pickett, Brett E.; Kumar, Sanjeev; Klem, Edward B.; Agnihothram, Sudhakar; Peter S Askovich; III, Armand Bankhead; Bolles, Meagen; Carter, Victoria; Chang, Jean; Clauss, Therese R.W.; Dash, Pradyot; Diercks, Alan H.; Eisfeld, Amie J.; Ellis, Amy

    2014-01-01

    The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe...

  10. Reply to Klitz and Niklasson: Can viral infections explain the cross-sectional Austrian diabetes data?

    OpenAIRE

    Thurner, S.; Klimek, P.(Department of Physics, Stockholm University, Stockholm, Sweden); Szell, M; Duftschmid, G.; Endel, G.; Kautzky-Willer, A.; Kasper, D.C.

    2013-01-01

    The vast majority of diabetes patients suffer from type II diabetes. There are several theories for potential causes of its development, the most favored being the "exhaustion" of beta-cells by chronic excess caloric intake combined with inactivity leading to obesity, diabetes, and cardiovascular disease. Viral infection could be a potential cause, however mainly for type I diabetes. Furthermore, autoimmunity might play a role in type I patients...

  11. Tunneling nanotubes: an alternate route for propagation of the bystander effect following oncolytic viral infection

    Directory of Open Access Journals (Sweden)

    Justin Ady

    2016-01-01

    Full Text Available Tunneling nanotubes (TNTs are ultrafine, filamentous actin-based cytoplasmic extensions which form spontaneously to connect cells at short and long-range distances. We have previously described long-range intercellular communication via TNTs connecting mesothelioma cells in vitro and demonstrated TNTs in intact tumors from patients with mesothelioma. Here, we investigate the ability of TNTs to mediate a viral thymidine kinase based bystander effect after oncolytic viral infection and administration of the nucleoside analog ganciclovir. Using confocal microscopy we assessed the ability of TNTs to propagate enhanced green fluorescent protein (eGFP, which is encoded by the herpes simplex virus NV1066, from infected to uninfected recipient cells. Using time-lapse imaging, we observed eGFP expressed in infected cells being transferred via TNTs to noninfected cells; additionally, increasing fluorescent activity in recipient cells indicated cell-to-cell transmission of the eGFP-expressing NV1066 virus had also occurred. TNTs mediated cell death as a form of direct cell-to-cell transfer following viral thymidine kinase mediated activation of ganciclovir, inducing a unique long-range form of the bystander effect through transmission of activated ganciclovir to nonvirus-infected cells. Thus, we provide proof-of-principle demonstration of a previously unknown and alternative mechanism for inducing apoptosis in noninfected recipient cells. The conceptual advance of this work is that TNTs can be harnessed for delivery of oncolytic viruses and of viral thymidine kinase activated drugs to amplify the bystander effect between cancer cells over long distances in stroma-rich tumor microenvironments.

  12. Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome

    Science.gov (United States)

    Kreins, Alexandra Y.; Ciancanelli, Michael J.; Okada, Satoshi; Kong, Xiao-Fei; Ramírez-Alejo, Noé; Kilic, Sara Sebnem; El Baghdadi, Jamila; Nonoyama, Shigeaki; Mahdaviani, Seyed Alireza; Ailal, Fatima; Bousfiha, Aziz; Mansouri, Davood; Nievas, Elma; Ma, Cindy S.; Rao, Geetha; Bernasconi, Andrea; Sun Kuehn, Hye; Niemela, Julie; Stoddard, Jennifer; Deveau, Paul; Cobat, Aurelie; El Azbaoui, Safa; Sabri, Ayoub; Lim, Che Kang; Sundin, Mikael; Avery, Danielle T.; Halwani, Rabih; Grant, Audrey V.; Boisson, Bertrand; Bogunovic, Dusan; Itan, Yuval; Moncada-Velez, Marcela; Martinez-Barricarte, Ruben; Migaud, Melanie; Deswarte, Caroline; Alsina, Laia; Kotlarz, Daniel; Klein, Christoph; Muller-Fleckenstein, Ingrid; Fleckenstein, Bernhard; Cormier-Daire, Valerie; Rose-John, Stefan; Picard, Capucine; Hammarstrom, Lennart; Puel, Anne; Al-Muhsen, Saleh; Abel, Laurent; Chaussabel, Damien; Rosenzweig, Sergio D.; Minegishi, Yoshiyuki; Tangye, Stuart G.; Bustamante, Jacinta; Casanova, Jean-Laurent

    2015-01-01

    Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17+ T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans. PMID:26304966

  13. IMBALANCE OF IMMUNOREGULATORY Th1- AND Th2-CYTOKINES IN PERSISTENT VIRAL INFECTIONS

    Directory of Open Access Journals (Sweden)

    I. O. Naslednikova

    2007-01-01

    Full Text Available Abstract. The article is considering certain features of immunopathogenesis exhibited in persistent viral infections, taking into account modern data and recently introduced immunological techniques. It has been revealed that a long-term persistence of hepatitis B and C viruses, tick-borne encephalitis, and herpes simplex is accompanied by deficient functioning in the T-cell compartment of immune system, and by markedly altered production of immunoregulatory cytokines in peripheral blood mononuclear leukocytes, mainly characterized by Th2 predominance.

  14. Latent viral immune inflammatory response model for chronic multisymptom illness.

    Science.gov (United States)

    Maloney, Sean R; Jensen, Susan; Gil-Rivas, Virginia; Goolkasian, Paula

    2013-03-01

    A latent viral immune inflammatory response (LVIIR) model is presented which integrates factors that contribute to chronic multisymptom illness (CMI) in both the veteran and civilian populations. The LVIIR model for CMI results from an integration of clinical experience with a review of the literature in four distinct areas: (1) studies of idiopathic multisymptom illness in the veteran population including two decades of research on Gulf War I veterans with CMI, (2) new evidence supporting the existence of chronic inflammatory responses to latent viral antigens and the effect these responses may have on the nervous system, (3) recent discoveries concerning the role of vitamin D in maintaining normal innate and adaptive immunity including suppression of latent viruses and regulation of the immune inflammatory response, and (4) the detrimental effects of extreme chronic repetitive stress (ECRS) on the immune and nervous systems. The LVIIR model describes the pathophysiology of a pathway to CMI and presents a new direction for the clinical assessment of CMI that includes the use of neurological signs from a physical exam, objective laboratory data, and a new proposed latent viral antigen-antibody imaging technique for the peripheral and central nervous system. The LVIIR model predicts that CMI can be treated by a focus on reversal of immune system impairment, suppression of latent viruses and their antigens, and healing of nervous system tissue damaged by chronic inflammation associated with latent viral antigens and by ECRS. In addition, the LVIIR model suggests that maintaining optimal serum 25 OH vitamin D levels will maximize immune system suppression of latent viruses and their antigens and will minimize immune system inflammation. This model also emphasizes the importance of decreasing ECRS to improve immune system function and to minimize nervous system injury from excess serum glucocorticoid levels. The proposed model supports growing evidence that increasing

  15. Varicella infection modeling.

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Katherine A.; Finley, Patrick D.; Moore, Thomas W.; Nozick, Linda Karen; Martin, Nathaniel; Bandlow, Alisa; Detry, Richard Joseph; Evans, Leland B.; Berger, Taylor Eugen

    2013-09-01

    Infectious diseases can spread rapidly through healthcare facilities, resulting in widespread illness among vulnerable patients. Computational models of disease spread are useful for evaluating mitigation strategies under different scenarios. This report describes two infectious disease models built for the US Department of Veteran Affairs (VA) motivated by a Varicella outbreak in a VA facility. The first model simulates disease spread within a notional contact network representing staff and patients. Several interventions, along with initial infection counts and intervention delay, were evaluated for effectiveness at preventing disease spread. The second model adds staff categories, location, scheduling, and variable contact rates to improve resolution. This model achieved more accurate infection counts and enabled a more rigorous evaluation of comparative effectiveness of interventions.

  16. The importance of viral blips and duration of therapy initiated in primary infection in maintaining viral control after stopping cART

    Science.gov (United States)

    Fidler, Sarah; Olson, Ashley; Fox, Julie; Phillips, Andrew; Morrison, Charles; Thornhill, John; Bucher, Heiner; Muga, Roberto; Porter, Kholoud

    2014-01-01

    Introduction After achieving undetectable HIV-RNA on cART, on cessation, HIV-RNA rebounds to pre-treatment values for the majority due to the presence of an inaccessible viral reservoir. There is some evidence that cART during primary HIV infection (PHI) limits the reservoir size, optimizing the chance of maintaining viral control off cART. Data are required to predict possible viral controllers for treatment interruption following cART. This analysis aims to investigate the effect of cART duration and the rate of viral blips while on cART initiated in PHI, and other factors on maintaining viral control for those stopping cART. Material and Methods Using CASCADE data on HIV seroconverters, we characterized virologic blip (viral suppression on cART followed by a single HIV-RNA above a blip threshold and a subsequent measure below the threshold without cART change) rates for those starting cART within six months of seroconversion (SC). Using Cox models, we examined the effect of the following factors on time to virologic rebound (HIV-RNA>1000) after cART stop: cART duration, severity/rate of blips on cART, time from SC to cART start, cART class, SC year, SC age, CD4 at cART start/stop, sex and HIV risk group. Results The 660 individuals initiating cART in PHI were mostly male (91%), seroconverting between 1995 and 2012, with a median (IQR) age of 34 (29, 41) years mostly infected through sex between men (73%). Median cART duration was 14.8 (7.0, 31.7) months initiated at a median 1.9 (0.5, 3.9) months post SC. 13 (11, 16), 9 (7, 11), 6 (5, 9) and 7 (6, 10)% of individuals experienced blips >50, 100, 200 and 400 copies/mL, respectively. Of those who experienced blips, most (77–90%, depending on blip threshold) experienced just one. Among 250 individuals with undetectable HIV-RNA at cART stop, median time to rebound was 1.6 (0.30, 5.8) months. Time on cART was the only factor independently associated with control after stopping, HR for rebound=0.91 (0.86, 0.98) per

  17. Household size is critical to varicella-zoster virus transmission in the tropics despite lower viral infectivity

    DEFF Research Database (Denmark)

    Nichols, Richard A; Averbeck, Karin T; Poulsen, Anja G;

    2011-01-01

    with viral genetic information on routes of infection, to obtain precise estimates of disease transmission within and between houses. This community contains many large households in which different families live under a single roof, in living quarters divided by partitions. Our data show that household...... that the epidemiology of chickenpox in tropical Guinea Bissau is dependent on the interaction of the social and physical environments. The distinctive clinical presentation of VZV and its ubiquitous distribution make it an attractive model for estimating the variables that contribute to global differences...... in the transmission of airborne viruses....

  18. Bovine viral diarrhea virus (BVDV) infection in dairy cattle herds in northeast Thailand.

    Science.gov (United States)

    Nilnont, Theerakul; Aiumlamai, Suneerat; Kanistanont, Kwankate; Inchaisri, Chaidate; Kampa, Jaruwan

    2016-08-01

    Bovine viral diarrhea virus causes a wide range of clinical manifestation with subsequent economic losses in dairy production worldwide. Our study of a population of dairy cattle in Thailand based on 933 bulk tank milk samples from nine public milk collection centers aimed to monitor infective status and to evaluate the effect of the infection in cows as well as to examine the reproductive performance of heifers to provide effective recommendations for disease control in Thailand. The results showed a moderate antibody-positive prevalence in the herd (62.5 %), with the proportion of class-3 herd, actively infected stage, being 17.3 %. Fourteen persistently infected (PI) animals were identified among 1196 young animals from the class-3 herds. Most of the identified PI animals, 11/14, were born in one sub-area where bovine viral diarrhea virus (BVDV) investigation has not been performed to date. With respect to reproductive performance, class-3 herds also showed higher median values of reproductive indices than those of class-0 herds. Cows and heifers in class-3 herds had higher odds ratio of calving interval (CI) and age at first service (AFS) above the median, respectively, compared to class-0 herds (OR = 1.29; P = 0.02 and OR = 1.63; P = 0.02). Our study showed that PI animals were still in the area that was previously studied. Furthermore, a newly studied area had a high prevalence of BVDV infection and the infection affected the reproductive performance of cows and heifers. Although 37.5 % of the population was free of BVDV, the lack of official disease prevention and less awareness of herd biosecurity may have resulted in continuing viral spread and silent economic losses have potentially occurred due to BVDV. We found that BVDV is still circulating in the region and, hence, a national control program is required.

  19. Review of Non-Bacterial Infections in Respiratory Medicine: Viral Pneumonia.

    Science.gov (United States)

    Galván, José María; Rajas, Olga; Aspa, Javier

    2015-11-01

    Although bacteria are the main pathogens involved in community-acquired pneumonia, a significant number of community-acquired pneumonia are caused by viruses, either directly or as part of a co-infection. The clinical picture of these different pneumonias can be very similar, but viral infection is more common in the pediatric and geriatric populations, leukocytes are not generally elevated, fever is variable, and upper respiratory tract symptoms often occur; procalcitonin levels are not generally affected. For years, the diagnosis of viral pneumonia was based on cell culture and antigen detection, but since the introduction of polymerase chain reaction techniques in the clinical setting, identification of these pathogens has increased and new microorganisms such as human bocavirus have been discovered. In general, influenza virus type A and syncytial respiratory virus are still the main pathogens involved in this entity. However, in recent years, outbreaks of deadly coronavirus and zoonotic influenza virus have demonstrated the need for constant alert in the face of new emerging pathogens. Neuraminidase inhibitors for viral pneumonia have been shown to reduce transmission in cases of exposure and to improve the clinical progress of patients in intensive care; their use in common infections is not recommended. Ribavirin has been used in children with syncytial respiratory virus, and in immunosuppressed subjects. Apart from these drugs, no antiviral has been shown to be effective. Prevention with anti-influenza virus vaccination and with monoclonal antibodies, in the case of syncytial respiratory virus, may reduce the incidence of pneumonia.

  20. INFLUENZA AND ACUTE VIRAL RESPIRATORY INFECTIONS IN THE PRACTICE OF THE EMERGENCY CREWS OF MOSCOW

    Directory of Open Access Journals (Sweden)

    N. F. Plavunov

    2016-01-01

    Full Text Available Influenza and acute viral respiratory infections have a great social significance during epidemic rise of morbidity and demand differential diagnosis of pneumonia with bacterial etiology and consultation with an infectious disease doctor in case of seeing patients in non-core hospitals. This article highlights the problem of influenza and acute respiratory viral infections’ early diagnosis. Clinical manifestations of influenza and other respiratory extremely similar. The differential diagnosis must take into account the presence of mixed infection in the same patient. According to the results of consultative infectious ambulance teams in 2014-2016, quality of diagnostics of this infectious pathology was examined. Observed deaths in persons later seeking medical treatment, not receiving timely antiviral therapy and related to high-risk groups: patients with obesity, chronic alcohol intoxication, diabetes, pregnant women. Influenza and acute viral respiratory infections, more complicated by pneumonia, people in the older age group, indicating the need for timely medical evacuation of patients older than 60 years. In some cases, in the diagnosis of influenza was helped by the results of laboratory studies (especially the trend to leukopenia and a positive rapid test. It should be noted that a negative rapid test for influenza was not a reason for exclusion of the diagnosis “influenza”.

  1. [The application of CRISPR-Cas9 gene editing technology in viral infection diseases].

    Science.gov (United States)

    Lijuan, Yin; Siqi, Hu; Fei, Guo

    2015-05-01

    The RNA-guided Cas9 nuclease from microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system has been used to facilitate efficient genome engineering in eukaryotic cells. The specific targeted genome is recognized and cut by gRNA-directed CRISPR/Cas9 complex, specifically by the endonuclease Cas9. The targeted gene locus could be repaired either by homology-directed repair or nonhomologous end joining, thus achieving a desired editing outcome. Viruses infect cells through specific receptors, and then the viral genome is transcribed, replicated and translated to complete its life cycle. As a result, some DNA virus and retrovirus genomes are integrated into the cellular genome. Gene therapy is a new trend to treat viral infected diseases. Given its designable sequence-specific editing of the targeted genome, CRISPR/Cas9 has tremendous potential in treating persistent and latent viral infections. In this review, we summarize the mechanism and progresses of CRISPR/Cas9, and also highlight its therapeutic application in infectious diseases.

  2. Simulated microgravity effects on the resistance of potato plants to viral infection

    Science.gov (United States)

    Mishchenko, L. T.; Gordyeichik, O. I.; Taran, O. P.

    Our earlier research results showed that prolonged clinostating impeded the reproduction of the wheat streak mosaic virus WSMV in artificially infected Apogee wheat plants The WSMW reproduction reduction leads to the formation of yield at the expense of the various physiologo-biochemical mechanisms of adaptation The results of our research activities open up the possibilities for the creation of new biotechnologies for both orbital and terrestrial conditions There arises a need to verify this phenomenon on potato plants which reproduce by tubers and in which viral infection unlike the WSMV is easily spread with planting material The initial parental potato plants were cultivated in a universal clinostat Cycle-2 and horizontal clinostat KG-8 on artificial substrate employing a balanced nutrient mixture of macro and microelements Viral antigens were detected in the organs of infected plants by a solid-phase immunoenzymatic analysis in its indirect das-ELISA variant sandwich variant A test system manufactured by the Bioreba firm Switzerland was employed for diagnostics The reader of the Termo Labsystems Opsis MR firm was employed for the measurements of optical density of the immunoenzymatic reaction product with a software of the Dynex Revelation Quicklik USA at wavelength of 405 630 nm Virion identification was carried out using the electron microscopy negative contrasting procedure Statistical data processing was performed using Excel AGROSTAT program We investigated the effects of clinostating on the development of viral

  3. Morphine increases hippocampal viral load and suppresses frontal lobe CCL5 expression in the LP-BM5 AIDS model.

    Science.gov (United States)

    McLane, Virginia D; Cao, Ling; Willis, Colin L

    2014-04-15

    Chronic opiate abuse accelerates the development of cognitive deficits in human immunodeficiency virus (HIV)-1 patients. To investigate morphine's effects on viral infection of the central nervous system, we applied chronic morphine treatment to the LP-BM5 murine acquired immunodeficiency syndrome (MAIDS) model. LP-BM5 infection induces proinflammatory cytokine/chemokine production, correlating to increased blood-brain barrier permeability. Morphine treatment significantly increased LP-BM5 viral load in the hippocampus, but not in the frontal lobe. Morphine reduced the chemokine CCL5 to non-infected levels in the frontal lobe, but not in the hippocampus. These data indicate a region-specific mechanism for morphine's effects on virally-induced neurocognitive deficits.

  4. Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

    Science.gov (United States)

    Goodwin, Thomas J.; Schneider, Sandra L.; MacIntosh, Victor; Gibbons, Thomas F.

    2010-01-01

    Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

  5. Four cases with Kawasaki disease and viral infection: aetiology or association.

    Science.gov (United States)

    Giray, Tuba; Biçer, Suat; Küçük, Öznur; Çöl, Defne; Yalvaç, Zerrin; Gürol, Yeşim; Yilmaz, Gülden; Saç, Ahmet; Mogol, Yigit

    2016-12-01

    The aetiology of Kawasaki disease has not yet been precisely determined. It has been associated with a variety of bacterial and viral agents. Some viruses including human adenovirus, coronavirus, and parainfluenza virus type 3 have been isolated from patients with Kawasaki disease. Clinical presentation of patients with human coronavirus and adenovirus infections mimics Kawasaki disease. In addition, these viruses may also be detected in Kawasaki disease as a coinfection. In this report, we present four Kawasaki disease patients infected with adenovirus, coronavirus OC43/HKU1 and parainfluenza virus type 3.

  6. Cofactor dependence and isotype distribution of anticardiolipin antibodies in viral infections

    OpenAIRE

    Guglielmone, H; Vitozzi, S; Elbarcha, O; E. Fernandez

    2001-01-01

    BACKGROUND—Antibodies to cardiolipin (aCLs) are often detected in patients with autoimmune disorders or infectious diseases.
OBJECTIVE—To investigate the distribution of aCL isotypes and requirement of protein cofactor in viral infections in order to establish the importance, if any, of these antibodies in these infectious diseases.
PATIENTS AND METHODS—The isotype distribution of aCLs in the sera from 160 patients with infection caused by HIV-1 (n=40), hepatitis A virus (n=40), hepatitis B v...

  7. Activated iNKT cells promote memory CD8+ T cell differentiation during viral infection.

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    Emma C Reilly

    Full Text Available α-Galactosylceramide (α-GalCer is the prototypical lipid ligand for invariant NKT cells. Recent studies have proposed that α-GalCer is an effective adjuvant in vaccination against a range of immune challenges, however its mechanism of action has not been completely elucidated. A variety of delivery methods have been examined including pulsing dendritic cells with α-GalCer to optimize the potential of α-GalCer. These methods are currently being used in a variety of clinical trials in patients with advanced cancer but cannot be used in the context of vaccine development against pathogens due to their complexity. Using a simple delivery method, we evaluated α-GalCer adjuvant properties, using the mouse model for cytomegalovirus (MCMV. We measured several key parameters of the immune response to MCMV, including inflammation, effector, and central memory CD8(+ T cell responses. We found that α-GalCer injection at the time of the infection decreases viral titers, alters the kinetics of the inflammatory response, and promotes both increased frequencies and numbers of virus-specific memory CD8(+ T cells. Overall, our data suggest that iNKT cell activation by α-GalCer promotes the development of long-term protective immunity through increased fitness of central memory CD8(+ T cells, as a consequence of reduced inflammation.

  8. Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems

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    Marta Trevisan

    2015-07-01

    Full Text Available The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs, which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host–pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

  9. DETECTION OF AUTOREACTIVE CLASS M ANTIBODIES IN PATIENTS WITH RESPIRATORY VIRAL INFECTIONS

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    V. Z. Krivitskaya

    2008-01-01

    Full Text Available Abstract. The aim of this study was to detect some features of autoreactive IgM production that interact with IgGs and normal human cellular antigens in blood sera of patients with acute respiratory viral infections caused by various factors, dependent on their age and clinical features of disease. The antibody concentrations were determined by immunoenzyme technique in paired serum samples from 750 patients and single specimens from 97 healthy persons. The results of analysis have shown that the studied types of autoreactive IgM represent a normal component of humoral immunity, since they are detectable in sufficient number of normal sera from healthy persons over 3 years old. In acute respiratory viral infections of different etiology, the rates of appropriate seroconversions comprised 0 to 16% for age cohort of < 3 years old. Incidence of seroconversions reached 37% among older children and adult patients with respiratory syncitial virus (RSV, or adenoviral infection, thus being 1.7 to 5.1-fold higher than in patients with influenza A, or B, or parainfluenza. In cases of clinical complications of RSV or parainfluenza infections (i.e., respiratory tract obstruction, or pneumonia, the rates of seroconversions to autoreactive IgMs was 1.4 to1.8-fold higher than among the patients with uncomplicated clinical course of these infections. (Med. Immunol., 2008, vol. 10, N 2-3, pp 229-238.

  10. The prevalence of the most important viral infections in renal transplant recipients in Serbia

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    Ćupić Maja

    2012-01-01

    Full Text Available Viruses are the main cause of opportunistic infections after kidney transplantation. The aim of this study was to determine the prevalence of cytomegalovirus (CMV, Epstein-Barr virus (EBV, B. K. virus (BKV and John Cunningham virus (JCV infections in renal transplant recipients (RTR. This retrospective study of 112 RTR investigated the presence of CMV, EBV and polyomaviruses DNA in plasma and/or urine by PCR. The visualization of PCR products was performed by electrophoresis on 2% agarose gel stained with ethidium bromide and photographed under a UV light. The chi-square test was used for statistical analysis. CMV DNA was detected in 14/112 (12.5%, EBV DNA in 4/49 (8.16%, BKV DNA in 10/31 (32.26% and JCV DNA in 3/31 (9.68% RTR. These results show that CMV infection is more often present in RTR compared to other investigated viral infections. In the light of these results, molecular testing could be useful in identifying recipients at high risk of symptomatic post-transplant viral infection. [Projekat Ministarstva nauke Republike Srbije, br. 175073, br. 175038 and br. 175089

  11. Yakammaoto inhibits enterovirus 71 infection by reducing viral attachment, internalization, replication, and translation

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    Chia-Feng Yeh

    2015-06-01

    Full Text Available Enterovirus 71 (EV71 can cause central nervous system infections with mortality and neurologic sequelae. At present, there is no effective therapeutic modality for EV71 infection. The infection is more common in families with poor socioeconomic status. Therefore, finding a readily available, cost-effective therapeutic modality would be very helpful to these socioeconomically disadvantaged families. Yakammaoto is a cheap and readily available traditional prescription that is proven to have antiviral activity against coxsackievirus B4 (CVB4. CVB4 and EV71 are enteroviruses. In this study, we evaluated the antiviral activity of hot water extract of yakammaoto against EV71. The results of plaque reduction assay and flow cytometry demonstrated that yakammaoto dose dependently inhibited EV71 infection. In addition, reverse transcription-polymerase chain reaction (RT-PCR and quantitative RT-PCR results showed that yakammaoto reduced viral replication. Western blotting analysis showed that yakammaoto can inhibit viral protein production. Thus, our results suggest that yakammaoto should be considered to manage EV71 infection in the future.

  12. Viral etiology and clinical profiles of children with severe acute respiratory infections in China.

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    Chen Zhang

    Full Text Available BACKGROUND: No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute respiratory infection (SARI in China during 2009 H1N1 pandemic and post-pandemic period. METHODS: Cohort of 370 hospitalized children (1 to 72 months with SARI from May 2008 to March 2010 was enrolled in this study. Nasopharyngeal aspirate (NPA specimens were tested by a commercial assay for 18 respiratory viral targets. The viral distribution and its association with clinical character were statistically analyzed. RESULTS: Viral pathogen was detected in 350 (94.29% of children with SARI. Overall, the most popular viruses were: enterovirus/rhinovirus (EV/RV (54.05%, respiratory syncytial virus (RSV (51.08%, human bocavirus (BoCA (33.78%, human parainfluenzaviruse type 3 (PIV3 (15.41%, and adenovirus (ADV (12.97%. Pandemic H1N1 was the dominant influenza virus (IFV but was only detected in 20 (5.41% of children. Moreover, detection rate of RSV and human metapneumovirus (hMPV among suburb participants were significantly higher than that of urban area (P<0.05. Incidence of VSARI among suburb participants was also significant higher, especially among those of 24 to 59 months group (P<0.05. CONCLUSION: Piconaviruses (EV/RV and paramyxoviruses are the most popular viral pathogens among children with SARI in this study. RSV and hMPV significantly increase the risk of SARI, especially in children younger than 24 months. Higher incidence of VSARI and more susceptibilities to RSV and hMPV infections were found in suburban patients.

  13. Leukotriene B4 induces release of antimicrobial peptides in lungs of virally infected mice.

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    Gaudreault, Eric; Gosselin, Jean

    2008-05-01

    Leukotriene B(4) (LTB(4)) is a lipid mediator of inflammation that was recently shown to exert antiviral activities. In this study, we demonstrate that the release of antimicrobial proteins by neutrophils contribute to an early host defense against influenza virus infection in vitro as well as in vivo. Daily i.v. treatments with LTB(4) lead to a significant decrease in lung viral loads at day 5 postinfection in mice infected with influenza A virus compared with the placebo-treated group. This reduction in viral load was not present in mice deficient in the high-affinity LTB(4) receptor. Viral clearance in lungs was associated with up-regulated presence of antimicrobial peptides such as beta-defensin-3, members of the mouse eosinophil-related RNase family, and the mouse cathelicidin-related antimicrobial peptide. Our results also indicate that neutrophils are important in the antiviral effect of LTB(4). Viral loads in neutrophil-depleted mice were not diminished by LTB(4) administration, and a substantial reduction in the presence of murine cathelicidin-related antimicrobial peptide and the murine eosinophil-related RNase family in lung tissue was observed. Moreover, in vitro treatment of human neutrophil cultures with LTB(4) led rapidly to the secretion of the human cathelicidin LL-37 and eosinophil-derived neurotoxin, known as antiviral peptides. Pretreatment of cell cultures with specific LTB(4) receptor antagonists clearly demonstrate the implication of the high-affinity LTB(4) receptor in the LTB(4)-mediated activity. Together, these results demonstrate the importance of neutrophils and the secretion of antimicrobial peptides during the early immune response mediated by LTB(4) against a viral pathogen.

  14. The role of viral and host microRNAs in the Aujeszky's disease virus during the infection process.

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    Oriol Timoneda

    Full Text Available Porcine production is a primary market in the world economy. Controlling swine diseases in the farm is essential in order to achieve the sector necessities. Aujeszky's disease is a viral condition affecting pigs and is endemic in many countries of the world, causing important economic losses in the swine industry. microRNAs (miRNAs are non-coding RNAs which modulates gene expression in animals, plants and viruses. With the aim of understanding miRNA roles during the Aujeszky's disease virus [ADV] (also known as suid herpesvirus type 1 [SuHV-1] infection, the expression profiles of host and viral miRNAs were determined through deep sequencing in SuHV-1 infected porcine cell line (PK-15 and in an animal experimental SuHV-1 infection with virulent (NIA-3 and attenuated (Begonia strains. In the in vivo approach miR-206, miR-133a, miR-133b and miR-378 presented differential expression between virus strains infection. In the in vitro approach, most miRNAs were down-regulated in infected groups. miR-92a and miR-92b-3p were up-regulated in Begonia infected samples. Functional analysis of all this over expressed miRNAs during the infection revealed their association in pathways related to viral infection processes and immune response. Furthermore, 8 viral miRNAs were detected by stem loop RT-qPCR in both in vitro and in vivo approaches, presenting a gene regulatory network affecting 59 viral genes. Most described viral miRNAs were related to Large Latency Transcript (LLT and to viral transcription activators EP0 and IE180, and also to regulatory genes regarding their important roles in the host-pathogen interaction during viral infection.

  15. The Role of Viral and Host MicroRNAs in the Aujeszky’s Disease Virus during the Infection Process

    Science.gov (United States)

    Timoneda, Oriol; Núñez-Hernández, Fernando; Balcells, Ingrid; Muñoz, Marta; Castelló, Anna; Vera, Gonzalo; Pérez, Lester J.; Egea, Raquel; Mir, Gisela; Córdoba, Sarai; Rosell, Rosa; Segalés, Joaquim; Tomàs, Anna; Sánchez, Armand; Núñez, José I.

    2014-01-01

    Porcine production is a primary market in the world economy. Controlling swine diseases in the farm is essential in order to achieve the sector necessities. Aujeszky’s disease is a viral condition affecting pigs and is endemic in many countries of the world, causing important economic losses in the swine industry. microRNAs (miRNAs) are non-coding RNAs which modulates gene expression in animals, plants and viruses. With the aim of understanding miRNA roles during the Aujeszky’s disease virus [ADV] (also known as suid herpesvirus type 1 [SuHV-1]) infection, the expression profiles of host and viral miRNAs were determined through deep sequencing in SuHV-1 infected porcine cell line (PK-15) and in an animal experimental SuHV-1 infection with virulent (NIA-3) and attenuated (Begonia) strains. In the in vivo approach miR-206, miR-133a, miR-133b and miR-378 presented differential expression between virus strains infection. In the in vitro approach, most miRNAs were down-regulated in infected groups. miR-92a and miR-92b-3p were up-regulated in Begonia infected samples. Functional analysis of all this over expressed miRNAs during the infection revealed their association in pathways related to viral infection processes and immune response. Furthermore, 8 viral miRNAs were detected by stem loop RT-qPCR in both in vitro and in vivo approaches, presenting a gene regulatory network affecting 59 viral genes. Most described viral miRNAs were related to Large Latency Transcript (LLT) and to viral transcription activators EP0 and IE180, and also to regulatory genes regarding their important roles in the host – pathogen interaction during viral infection. PMID:24475202

  16. Aedes mosquito salivary immune peptides:boost or block dengue viral infections

    Institute of Scientific and Technical Information of China (English)

    Natthanej Luplertlop

    2014-01-01

    Dengue virus, one of the most important arthropod-borne viruses, infected to human can severely cause dengue hemorrhagic fever and dengue shock syndrome. There are expected about 50 million dengue infections and 500 000 individuals are hospitalized with dengue hemorrhagic fever, mainly in Southeast Asia, Pacific, and in Americas reported each year. The rapid expansion of global dengue is one of a major public health challenge, together with not yet successful solutions of dengue epidemic control strategies. Thus, these dynamic dengue viral infections exhibited high demographic, societal, and public health infrastructure impacts on human. This review aimed to highlight the current understanding of dengue mosquito immune responses and role of mosquito salivary glands on dengue infection. These information may provide a valuable knowledge of disease pathogenesis, especially in mosquito vector and dengue virus interaction, which may help to control and prevent dengue distribution.

  17. Aedes mosquito salivary immune peptides: boost or block dengue viral infections

    Directory of Open Access Journals (Sweden)

    Natthanej Luplertlop

    2014-02-01

    Full Text Available Dengue virus, one of the most important arthropod-borne viruses, infected to human can severely cause dengue hemorrhagic fever and dengue shock syndrome. There are expected about 50 million dengue infections and 500 000 individuals are hospitalized with dengue hemorrhagic fever, mainly in Southeast Asia, Pacific, and in Americas reported each year. The rapid expansion of global dengue is one of a major public health challenge, together with not yet successful solutions of dengue epidemic control strategies. Thus, these dynamic dengue viral infections exhibited high demographic, societal, and public health infrastructure impacts on human. This review aimed to highlight the current understanding of dengue mosquito immune responses and role of mosquito salivary glands on dengue infection. These information may provide a valuable knowledge of disease pathogenesis, especially in mosquito vector and dengue virus interaction, which may help to control and prevent dengue distribution.

  18. The potential influence of common viral infections diagnosed during hospitalization among critically ill patients in the United States.

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    Makesha Miggins

    Full Text Available Viruses are the most common source of infection among immunocompetent individuals, yet they are not considered a clinically meaningful risk factor among the critically ill. This work examines the association of viral infections diagnosed during the hospital stay or not documented as present on admission to the outcomes of ICU patients with no evidence of immunosuppression on admission. This is a population-based retrospective cohort study of University HealthSystem Consortium (UHC academic centers in the U.S. from the years 2006 to 2009. The UHC is an alliance of over 90% of the non-profit academic medical centers in the U.S. A total of 209,695 critically ill patients were used in this analysis. Eight hospital complications were examined. Patients were grouped into four cohorts: absence of infection, bacterial infection only, viral infection only, and bacterial and viral infection during same hospital admission. Viral infections diagnosed during hospitalization significantly increased the risk of all complications. There was also a seasonal pattern for viral infections. Specific viruses associated with poor outcomes included influenza, RSV, CMV, and HSV. Patients who had both viral and bacterial infections during the same hospitalization had the greatest risk of mortality RR 6.58, 95% CI (5.47, 7.91; multi-organ failure RR 8.25, 95% CI (7.50, 9.07; and septic shock RR 271.2, 95% CI (188.0, 391.3. Viral infections may play a significant yet unrecognized role in the outcomes of ICU patients. They may serve as biological markers or play an active role in the development of certain adverse complications by interacting with coincident bacterial infection.

  19. Whole-body analysis of a viral infection: vascular endothelium is a primary target of infectious hematopoietic necrosis virus in zebrafish larvae.

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    Marion Ludwig

    Full Text Available The progression of viral infections is notoriously difficult to follow in whole organisms. The small, transparent zebrafish larva constitutes a valuable system to study how pathogens spread. We describe here the course of infection of zebrafish early larvae with a heat-adapted variant of the Infectious Hematopoietic Necrosis Virus (IHNV, a rhabdovirus that represents an important threat to the salmonid culture industry. When incubated at 24 °C, a permissive temperature for virus replication, larvae infected by intravenous injection died within three to four days. Macroscopic signs of infection followed a highly predictable course, with a slowdown then arrest of blood flow despite continuing heartbeat, followed by a loss of reactivity to touch and ultimately by death. Using whole-mount in situ hybridization, patterns of infection were imaged in whole larvae. The first infected cells were detectable as early as 6 hours post infection, and a steady increase in infected cell number and staining intensity occurred with time. Venous endothelium appeared as a primary target of infection, as could be confirmed in fli1:GFP transgenic larvae by live imaging and immunohistochemistry. Disruption of the first vessels took place before arrest of blood circulation, and hemorrhages could be observed in various places. Our data suggest that infection spread from the damaged vessels to underlying tissue. By shifting infected fish to a temperature of 28 °C that is non-permissive for viral propagation, it was possible to establish when virus-generated damage became irreversible. This stage was reached many hours before any detectable induction of the host response. Zebrafish larvae infected with IHNV constitute a vertebrate model of an hemorrhagic viral disease. This tractable system will allow the in vivo dissection of host-virus interactions at the whole organism scale, a feature unrivalled by other vertebrate models.

  20. Using double-stranded RNA to prevent in vitro and in vivo viral infections by recombinant baculovirus.

    Science.gov (United States)

    Valdes, Victor Julian; Sampieri, Alicia; Sepulveda, Jorge; Vaca, Luis

    2003-05-23

    Introduction of double-stranded RNA (dsRNA) into a wide variety of cells and organisms results in post-transcriptional depletion of the homologue endogenous mRNA. This well-preserved phenomenon known as RNA interference (RNAi) is present in evolutionarily diverse organisms such as plants, fungi, insects, metazoans, and mammals. Because the identification of the targeted mRNA by the RNAi machinery depends upon Watson-Crick base-pairing interactions, RNAi can be exquisitely specific. We took advantage of this powerful and flexible technique to demonstrate that selective silencing of genes essential for viral propagation prevents in vitro and in vivo viral infection. Using the baculovirus Autographa californica, a rapidly replicating and highly cytolytic double-stranded DNA virus that infects many different insect species, we show for the first time that introduction of dsRNA from gp64 and ie1, two genes essential for baculovirus propagation, results in prevention of viral infection in vitro and in vivo. This is the first report demonstrating the use of RNAi to inhibit a viral infection in animals. This inhibition was specific, because dsRNA from the polyhedrin promoter (used as control) or unrelated dsRNAs did not affect the time course of viral infection. The most relevant consequences from the present study are: 1) RNAi offers a rapid and efficient way to interfere with viral genes to assess the role of specific proteins in viral function and 2) using RNAi to interfere with viral genes essential for cell infection may provide a powerful therapeutic tool for the treatment of viral infections.

  1. Single-cell analysis shows that paracrine signaling by first responder cells shapes the interferon-β response to viral infection.

    Science.gov (United States)

    Patil, Sonali; Fribourg, Miguel; Ge, Yongchao; Batish, Mona; Tyagi, Sanjay; Hayot, Fernand; Sealfon, Stuart C

    2015-02-10

    Immune responses to viral infection are stochastic processes, which initiate in a limited number of cells that then propagate the response. A key component of the response to viral infection entails the synthesis and secretion of type I interferons (IFNs), including the early induction of the gene encoding IFN-β (Ifnb1). With single-cell analysis and mathematical modeling, we investigated the mechanisms underlying how increases in the amount of Ifnb1 mRNA per cell and in the numbers of cells expressing Ifnb1 calibrate the response to viral infection. We used single-cell, single-molecule assays to quantify the early induction of Ifnb1 expression (the Ifnb1 response) in human monocyte-derived dendritic cells infected with Newcastle disease virus, thus retaining the physiological stoichiometry of transcriptional regulators to both alleles of the Ifnb1 gene. We applied computational methods to extract the stochastic features that underlie the cell-to-cell variations in gene expression over time. Integration of simulations and experiments identified the role of paracrine signaling in increasing the number of cells that express Ifnb1 over time and in calibrating the immune response to viral infection. Copyright © 2015, American Association for the Advancement of Science.

  2. Prevention and treatment of viral respiratory infections by traditional Chinese herbs

    Institute of Scientific and Technical Information of China (English)

    Wang Xiaoguang; Liu Zejing

    2014-01-01

    Objective This review focuses on current knowledge of traditional Chinese herbs on prevention and treatment of viral respiratory infections,especially caused by Severe Acute Respiratory Syndromes (SARS) virus,respiratory syncytial virus (RSV) and influenza viruses.Data sources The data used in this review were obtained from PubMed and CNKI up to May 2013.Terms of Chinese herbs and infections of respiratory tract were used in the search.Study selection Articles related that Chinese herbs preventing and treating infections in respiratory tract were retrieved and reviewed.The risk of bias of included studies was assessed by the method in the "Cochrane Handbook of Systematic Reveiws of Interventionsand studies" with high risk of bias were excluded.Four criteria for selections were set as following:randomized controlled trial,particular effective compound or derivative,reproducible result and animal test.Results Infectious respiratory tract diseases cause most mortality among infectious illnesses around the world.As traditional medicines,Chinese herbs have been widely used to deal with diseases for centuries and have been proved effective in practice.The administration of some Chinese herbs stimulates,suppresses or regulates the activity of immune system,thus protecting the respiratory tract or relieving infections of pathogens.Many herbs have remarkable antiviral effects,therefore they are used as substitutes of antimicrobial drugs.Based on the theory of traditional Chinese medicine,mix-using herbs provide a synergistic benefit on preventing and healing respiratory tract infections.Many commercial herbal medicines containing one or more compounds have been successfully applied to prevent and treat viral infections of respiratory tract clinically.Conclusions Traditional Chinese herbs could directly inhibit pathogens infecting respiratory tract,or coordinate the activity of immune system to avoid or relieve infections.With the emergence of antidrug pathogens or new

  3. Increasing P limitation and viral infection impact lipid remodeling of the picophytoplankter Micromonas pusilla

    Science.gov (United States)

    Maat, Douwe S.; Bale, Nicole J.; Hopmans, Ellen C.; Sinninghe Damsté, Jaap S.; Schouten, Stefan; Brussaard, Corina P. D.

    2016-03-01

    The intact polar lipid (IPL) composition of phytoplankton is plastic and dependent on environmental factors. Previous studies have shown that phytoplankton under low phosphorus (P) availability substitutes phosphatidylglycerols (PGs) with sulfoquinovosyldiacylglycerols (SQDGs) and digalactosyldiacylglycerols (DGDGs). However, these studies focused merely on P depletion, while phytoplankton in the natural environment often experience P limitation whereby the strength depends on the supply rate of the limiting nutrient. Here we report on the IPL composition of axenic cultures of the picophotoeukaryote Micromonas pusilla under different degrees of P limitation, i.e., P-controlled chemostats at 97 and 32 % of the maximum growth rate, and P starvation (obtained by stopping P supply to these chemostats). P-controlled cultures were also grown at elevated partial carbon dioxide pressure (pCO2) to mimic a future scenario of strengthened vertical stratification in combination with ocean acidification. Additionally, we tested the influence of viral infection for this readily infected phytoplankton host species. Results show that both SQDG : PG and DGDG : PG ratios increased with enhanced P limitation. Lipid composition was, however, not affected by enhanced (750 vs. 370 µatm) pCO2. In the P-starved virally infected cells the increase in SQDG : PG and DGDG : PG ratios was lower, whereby the extent depended on the growth rate of the host cultures before infection. The lipid membrane of the virus MpV-08T itself lacked some IPLs (e.g., monogalactosyldiacylglycerols; MGDGs) in comparison with its host. This study demonstrates that, besides P concentration, also the P supply rate, viral infection and even the history of the P supply rate can affect phytoplankton lipid composition (i.e., the non-phospholipid : phospholipid ratio), with possible consequences for the nutritional quality of phytoplankton.

  4. Can information be spread as a virus? viral marketing as epidemiological model

    Science.gov (United States)

    Rodrigues, Helena Sofia; Fonseca, Manuel José

    2016-11-01

    In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of the critical factors to this communications strategy effectiveness remain largely unknown, the mathematical models in epidemiology are presented in this marketing specific field. In this paper, an epidemiological model SIR (Susceptible- Infected-Recovered) to study the effects of a viral marketing strategy is presented. It is made a comparison between the disease parameters and the marketing application, and Matlab simulations are performed. Finally, some conclusions are carried out and their marketing implications are exposed: interactions across the parameters suggest some recommendations to marketers, as the profitability of the investment or the need to improve the targeting criteria of the communications campaigns.

  5. Alteration of viral lipid composition by expression of the phospholipid floppase ABCB4 reduces HIV vector infectivity

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    van Til Niek P

    2008-02-01

    Full Text Available Abstract Background The presence of cholesterol in the Human Immunodeficiency Virus (HIV lipid envelop is important for viral function as cholesterol depleted viral particles show reduced infectivity. However, it is less well established whether other viral membrane lipids are also important for HIV infection. The ABCB4 protein is a phosphatidyl choline (PC floppase that mediates transport of PC from the inner to the outer membrane leaflet. This property enabled us to modulate the lipid composition of HIV vectors and study the effects on membrane composition and infection efficiency. Results Virus generated in the presence of ABCB4 was enriched in PC and cholesterol but contained less sphingomyelin (SM. Viral titers were reduced 5.9 fold. These effects were not observed with an inactive ABCB4 mutant. The presence of the ABC transport inhibitor verapamil abolished the effect of ABCB4 expression on viral titers. The ABCB4 mediated reduction in infectivity was caused by changes in the viral particles and not by components co purified with the virus because virus made in the presence of ABCB4 did not inhibit virus made without ABCB4 in a competition assay. Incorporation of the envelope protein was not affected by the expression of ABCB4. The inhibitory effect of ABCB4 was independent of the viral envelope as the effect was observed with two different envelope proteins. Conclusion Our data indicate that increasing the PC content of HIV particles reduces infectivity.

  6. Viral Infections

    Science.gov (United States)

    ... illnesses such as HIV/AIDS, smallpox, and Ebola. Viruses are like hijackers. They invade living, normal cells and use those cells to multiply and produce other viruses like themselves. This can kill, damage, or change ...

  7. Respiratory dysfunction and proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis.

    Science.gov (United States)

    Bonville, Cynthia A; Bennett, Nicholas J; Koehnlein, Melissa; Haines, Deborah M; Ellis, John A; DelVecchio, Alfred M; Rosenberg, Helene F; Domachowske, Joseph B

    2006-05-25

    We explore relationships linking clinical symptoms, respiratory dysfunction, and local production of proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis. With a reduced inoculum of this natural rodent pathogen, we observe virus clearance by day 9, while clinical symptoms and respiratory dysfunction persist through days 14 and 17 postinoculation, respectively. Via microarray and ELISA, we identify expression profiles of proinflammatory mediators MIP-1alpha, MCP-1, and MIP-2 that correlate with persistent respiratory dysfunction. MIP-1alpha is localized in bronchial epithelium, which is also the major site of PVM replication. Interferon-gamma was detected in lung tissue, but at levels that do not correlate with respiratory dysfunction. Taken together, we present a modification of our pneumovirus infection model that results in improved survival and data that stand in support of a connection between local production of specific mediators and persistent respiratory dysfunction in the setting of acute viral bronchiolitis.

  8. Hepatitis A virus-encoded miRNAs attenuate the accumulation of viral genomic RNAs in infected cells.

    Science.gov (United States)

    Shi, Jiandong; Sun, Jing; Wu, Meini; Hu, Ningzhu; Hu, Yunzhang

    2016-06-01

    The establishment of persistent infection with hepatitis A virus (HAV) is the common result of most HAV/cell culture systems. Previous observations show that the synthesis of viral RNAs is reduced during infection. However, the underlying mechanism is poorly understood. We characterized three HAV-encoded miRNAs in our previous study. In this study, we aim to investigate the impact of these miRNAs on the accumulation of viral RNAs. The results indicated that the synthesis of viral genomic RNAs was dramatically reduced (more than 75 % reduction, P viral miRNA mimics. Conversely, they were significantly increased (more than 3.3-fold addition, P viral miRNA inhibitors. The luciferase reporter assay of miRNA targets showed that viral miRNAs were fully complementary to specific sites of the viral plus or minus strand RNA and strongly inhibited their expressions. Further data showed that the relative abundance of viral genomic RNA fragments that contain miRNA targets was also dramatically reduced (more than 80 % reduction, P viral miRNAs were overexpressed with miRNA mimics. In contrast, they were significantly increased (approximately 2-fold addition, P viral miRNAs were inhibited with miRNA inhibitors. In conclusion, these data suggest a possible mechanism for the reduction of viral RNA synthesis during HAV infection. Thus, we propose that it is likely that RNA virus-derived miRNA could serve as a self-mediated feedback regulator during infection.

  9. Double-stranded RNA viral infection of Trichomonas vaginalis infecting patients attending a sexually transmitted diseases clinic.

    Science.gov (United States)

    Wendel, Karen A; Rompalo, Anne M; Erbelding, Emily J; Chang, T-H; Alderete, John F

    2002-08-15

    Trichomonas vaginalis (TV) can be infected with double-stranded RNA (dsRNA) viruses that may have important implications for trichomonal virulence and disease pathogenesis. A cross-sectional study was conducted in a sexually transmitted diseases clinic to determine the prevalence and clinical significance of dsRNA viral infection of TV infecting men and women. Overall, dsRNA virus was present in 21 (75%) of 28 TV isolates (95% confidence interval [CI], 55%-89%). dsRNA viral infection of TV was not associated with the presence of discharge, dysuria, genital pruritus, or genital irritation or odor. However, patients with virus-positive isolates were significantly older than patients with virus-negative isolates (median age, 38 vs. 23 years; P=.003), and virus-positive isolates were more prevalent among women (19 [86%] of 22 isolates; 95% CI, 65%-97%) than among men (2 [33%] of 6 isolates; P=.02). The age and sex specificity of virus-positive isolates may aid in understanding the differences in chronicity and clinical presentation of TV in men and women.

  10. Contribution of Viral Mimics of Cellular Genes to KSHV Infection and Disease

    Directory of Open Access Journals (Sweden)

    Shuhei Sakakibara

    2014-09-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV, also named Human herpesvirus 8 HHV-8 is the cause of Kaposi sarcoma (KS, the most common malignancy in HIV-infected individuals worldwide, primary effusion lymphoma (PEL and multicentric Castleman disease (MCD. KSHV is a double-stranded DNA virus that encodes several homologues of cellular proteins. The structural similarity between viral and host proteins explains why some viral homologues function as their host counterparts, but sometimes at unusual anatomical sites and inappropriate times. In other cases, structural modification in the viral proteins can suppress or override the function of the host homologue, contributing to KSHV-related diseases. For example, viral IL-6 (vIL-6 is sufficiently different from human IL-6 to activate gp130 signaling independent of the α subunit. As a consequence, vIL-6 can activate many cell types that are unresponsive to cellular IL-6, contributing to MCD disease manifestations. Here, we discuss the molecular biology of KSHV homologues of cellular products as conduits of virus/host interaction with a focus on identifying new strategies for therapy of KS and other KSHV-related diseases.

  11. Rainbow trout surviving infections of viral haemorrhagic septicemia virus (VHSV) show lasting antibodies to recombinant G protein fragments

    DEFF Research Database (Denmark)

    Encinas, P.; Gomez-Casado, E.; Grandes, Fregeneda

    2011-01-01

    Rainbow trout antibodies (Abs) binding to recombinant fragments (frgs) derived from the protein G of the viral haemorrhagic septicemia virus (VHSV)-07.71 strain, could be detected by ELISA (frg-ELISA) in sera from trout surviving laboratory-controlled infections. Abs were detected not only by using...... infections. The viral frgs approach might also be used with other fish species and/or viruses....

  12. Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells

    Science.gov (United States)

    Iordanskiy, Sergey; Van Duyne, Rachel; Sampey, Gavin C; Woodson, Caitlin M; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao; Romerio, Fabio; Kashanchi, Fatah

    2015-01-01

    The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4+ T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4+ T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4+ T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. PMID:26184775

  13. A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model.

    Directory of Open Access Journals (Sweden)

    Iart Luca Shytaj

    Full Text Available Stably suppressed viremia during ART is essential for establishing reliable simian models for HIV/AIDS. We tested the efficacy of a multidrug ART (highly intensified ART in a wide range of viremic conditions (10³-10⁷ viral RNA copies/mL in SIVmac251-infected rhesus macaques, and its impact on the viral reservoir. Eleven macaques in the pre-AIDS stage of the disease were treated with a multidrug combination (highly intensified ART consisting of two nucleosidic/nucleotidic reverse transcriptase inhibitors (emtricitabine and tenofovir, an integrase inhibitor (raltegravir, a protease inhibitor (ritonavir-boosted darunavir and the CCR5 blocker maraviroc. All animals stably displayed viral loads below the limit of detection of the assay (i.e. <40 RNA copies/mL after starting highly intensified ART. By increasing the sensitivity of the assay to 3 RNA copies/mL, viral load was still below the limit of detection in all subjects tested. Importantly, viral DNA resulted below the assay detection limit (<2 copies of DNA/5*10⁵ cells in PBMCs and rectal biopsies of all animals at the end of the follow-up, and in lymph node biopsies from the majority of the study subjects. Moreover, highly intensified ART decreased central/transitional memory, effector memory and activated (HLA-DR⁺ effector memory CD4⁺ T-cells in vivo, in line with the role of these subsets as the main cell subpopulations harbouring the virus. Finally, treatment with highly intensified ART at viral load rebound following suspension of a previous anti-reservoir therapy eventually improved the spontaneous containment of viral load following suspension of the second therapeutic cycle, thus leading to a persistent suppression of viremia in the absence of ART. In conclusion, we show, for the first time, complete suppression of viral load by highly intensified ART and a likely associated restriction of the viral reservoir in the macaque AIDS model, making it a useful platform for testing

  14. Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer

    Science.gov (United States)

    Paiva, Leticia R.; Silva, Hallan S.; Ferreira, Silvio C.; Martins, Marcelo L.

    2013-04-01

    Oncolytic virotherapy—the use of viruses that specifically kill tumor cells—is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In this paper, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD8+ T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice.

  15. Mitochondrial bioenergetic alterations in mouse neuroblastoma cells infected with Sindbis virus: implications to viral replication and neuronal death.

    Directory of Open Access Journals (Sweden)

    Leandro Silva da Costa

    Full Text Available The metabolic resources crucial for viral replication are provided by the host. Details of the mechanisms by which viruses interact with host metabolism, altering and recruiting high free-energy molecules for their own replication, remain unknown. Sindbis virus, the prototype of and most widespread alphavirus, causes outbreaks of arthritis in humans and serves as a model for the study of the pathogenesis of neurological diseases induced by alphaviruses in mice. In this work, respirometric analysis was used to evaluate the effects of Sindbis virus infection on mitochondrial bioenergetics of a mouse neuroblastoma cell lineage, Neuro 2a. The modulation of mitochondrial functions affected cellular ATP content and this was synchronous with Sindbis virus replication cycle and cell death. At 15 h, irrespective of effects on cell viability, viral replication induced a decrease in oxygen consumption uncoupled to ATP synthesis and a 36% decrease in maximum uncoupled respiration, which led to an increase of 30% in the fraction of oxygen consumption used for ATP synthesis. Decreased proton leak associated to complex I respiration contributed to the apparent improvement of mitochondrial function. Cellular ATP content was not affected by infection. After 24 h, mitochondria dysfunction was clearly observed as maximum uncoupled respiration reduced 65%, along with a decrease in the fraction of oxygen consumption used for ATP synthesis. Suppressed respiration driven by complexes I- and II-related substrates seemed to play a role in mitochondrial dysfunction. Despite the increase in glucose uptake and glycolytic flux, these changes were followed by a 30% decrease in ATP content and neuronal death. Taken together, mitochondrial bioenergetics is modulated during Sindbis virus infection in such a way as to favor ATP synthesis required to support active viral replication. These early changes in metabolism of Neuro 2a cells may form the molecular basis of neuronal

  16. Association of genotypes with viral load and biochemical markers in HCV-infected Sindhi patients

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    Saba Riaz

    Full Text Available Abstract The presented study had two objectives. The first was to examine distributions of Hepatitis C Virus (HCV genotypes in Sindh, Pakistan, where HCV is prevalent. The other was to explore clinically relevant relationships between the genotypes, viral load (measured by real-time polymerase chain reaction assays and biochemical markers. For this, 1471 HCV-infected patients in six cities in Sindh were recruited and sampled. HCV genotype distributions varied among the cities, but genotype 3a was most prevalent, followed by 3b, 1a and 1b (detected in 51.5, 22.7. 9.25 and 3.2% of the cases, respectively. No type-specific sequences were detected in serum samples from 189 (12.8% of the 1471 patients. Frequencies of low (600,000 IU/mL serum viral loads were respectively 45.4, 16.5 and 38.1% for patients infected with genotype 3, and 16.9, 36.9 and 46.2%, respectively, for patients with other genotypes. Infection with genotype 1a was associated with significantly higher (p < 0.005 alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase titers than infection with genotype 3a. The results will help in the formulation of treatment strategies.

  17. New Insights into Type I Interferon and the Immunopathogenesis of Persistent Viral Infections

    Science.gov (United States)

    Snell, Laura M.; Brooks, David G.

    2015-01-01

    Most viruses generate potent T cell responses that rapidly control infection. However, certain viruses can subvert the immune response to establish persistent infections. The inability to clear virus induces an immunosuppressive program leading to the sustained expression of many immunoregulatory molecules that down-regulate T cell responses. Further, viral persistence is associated with multiple immune dysfunctions including lymphoid disorganization, defective antigen presentation, aberrant B cell responses and hypergammaglobulinemia. Although best known for its antiviral activity, recent data has highlighted the role of type I IFN (IFN-I) signaling as a central mediator of immunosuppression during viral persistence. It is also becoming increasingly apparent that many of the immune dysfunctions during persistent virus infection can be attributed directly or indirectly to the effects of chronic IFN-I signaling. This review explores the increasingly complex role of IFN-I in the regulation of immunity against persistently replicating virus infections and examines current and potential uses of IFN-I and blockade of IFN-I signaling to dampen chronic inflammation and activation in the clinic. PMID:25771184

  18. 外体和病毒感染%The Role of Exosomes in Viral Infection

    Institute of Scientific and Technical Information of China (English)

    张晓阳; 董春艳; 段铭

    2014-01-01

    外体(exosome)是源自细胞内体的小囊泡,可由多种哺乳动物细胞分泌释放,其组分包括蛋白质、脂质、mRNA和microRNA,是细胞间“通讯”交互的工具之一。我们以介绍外体的组成和生物发生为基础,综述了近年来其在病毒感染致病中的研究成果,以期为病毒感染致病机理的研究提供新的切入点。%The exosome, as a nano vesicle that buds from the endosomal compartment, is produced and re-leased by all kinds of mammalian cells. This vesicle contains a variety of proteins, lipids, mRNA and microRNA. These components are specific to the origin of the exosomes and contribute to cell-cell communications. Most of the exosomes involved in viral infection can either spread or limit an infection based on the type of virus and its target cells. In this review, we introduced the exosome, its origin and function, then we discussed its roles in vi-ral infection which is involved in the fate of the infection.

  19. Diverse uses of feathers with emphasis on diagnosis of avian viral infections and vaccine virus monitoring

    Directory of Open Access Journals (Sweden)

    I Davidson

    2009-09-01

    Full Text Available The large amounts of feathers produced by the poultry industry, that is considered as a waste was explored for possible uses in various industries, such as meals for animals, biofuels, biodegradable plastic materials, combating water pollution and more. That review mentions these uses, but concentrate on the utilization of feathers for the diagnosis of viral infections and for monitoring vaccine viruses in chickens after vaccination. The viral diseases in which diagnosis using nucleic acids extracted from the feather shafts was described are, Marek's disease virus, circoviruses, chicken anemia virus, fowlpox virus, avian retroviruses, avian influenza virus and infectious laryngotracheitis virus. In two cases, of Marek's disease virus and of infectious laryngotracheitis virus, the differentiation of vaccine and wild-type viruses from feather shafts was made possible, thus allowing for monitoring the vaccination efficacy. The present review demonstrates also the stability of DNA viruses in feather shafts, and the possible evaluation of environmental dissemination of pathogens. When viruses are transmitted vertically, like in the cases of the retrovirus REV, a teratogenic effect on the development of feathers of the day-old newly hatched chick might occur in the case of avian influenza and the chicken anemia virus, which might indicate on a viral infection.

  20. A serologic survey of viral infections in captive ungulates in Turkish zoos.

    Science.gov (United States)

    Yeşilbağ, Kadir; Alpay, Gizem; Karakuzulu, Hatice

    2011-03-01

    Zoos and zoologic gardens make optimal environments for interspecies transmission of viral infections. There are seven zoos and several small zoologic collections in Turkey. This study aimed to determine the current status of viral infections in captive ungulates living in these environments. Blood samples were taken from 163 captive animals from two zoos. There were 39 Cameroon sheep (Ovis ammon f aries), 11 Barbary sheep (Ammotragus lervia), 57 pygmy goats (Capra hircus), 9 Angora goats (Capra hircus), 21 mountain goats (Capra aegagrus-aegagrus), 7 llamas (Lama glama), 8 Persian goitred gazelle (Gazella subgutturosa subgutturosa), 7 Caspian red deer (Cervus elaphus maral), 2 fallow deer (Dama dama), and 2 camels (Camelus dromedarius). Antibodies against bovine viral diarrhea virus (BVDV), bovine herpesvirus-1 (BHV-1), bovine adenoviruses (BAV-1 and -3), parainfluenzavirus 3 (PI-3), and bluetongue viruses (BTV-4 and -9) were investigated using the virus neutralization test, and malignant catarrhal fever (MCF) antibodies were screened by ELISA. All animals were negative for BVDV and BHV-1 antibodies. Seroprevalence of BAV-1, BAV-3, PI-3, BRSV, BT-4, BT-9, and MCF were detected as follows: 46.6%, 60.1%, 0.6%, 7.3%, 1.8%, 1.2%, and 51.6%, respectively. Seroprevalence of BAVs and MCF were more common than all other viruses (P zoo animals are at risk for BTV in endemic regions.

  1. Comparison of asymptomatic and symptomatic rhinovirus infections in university students: incidence, species diversity, and viral load.

    Science.gov (United States)

    Granados, Andrea; Goodall, Emma C; Luinstra, Kathy; Smieja, Marek; Mahony, James

    2015-08-01

    Human rhinovirus (HRV) infections are common but poorly characterized in university students. Thus, we characterized asymptomatic and symptomatic HRV infections by incidence, species diversity, and viral load of 502 university students during September and October of 2010 and 2011 from nasal swabs and electronically submitted symptom questionnaires. We tested all symptomatic students and randomly sampled participants who remained asymptomatic (n=25/week, over 8 weeks each study year) on a weekly basis by real-time PCR and sequenced HRV positives. HRV was identified in 33/400 (8.3%) and 85/92 (92.4%) of the asymptomatic and symptomatic students, respectively. We identified a higher than previously reported rate of HRV-B in both groups, although the distribution of HRV species was similar (P=0.37). Asymptomatic viral load averaged 1.2 log10 copies/mL lower than symptomatic HRV (P<0.001). In conclusion, asymptomatic HRV activity preceded peak symptomatic activity in September and October and was associated with lower viral load.

  2. Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-β Activity

    Science.gov (United States)

    Radwan, Asmaa; Keenan, Christine R.; Langenbach, Shenna Y.; Li, Meina; Londrigan, Sarah L.; Gualano, Rosa C.; Stewart, Alastair G.

    2017-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly associated with respiratory syncytial virus (RSV), rhinovirus (RV) and influenza A virus (IAV) infection. The ensuing airway inflammation is resistant to the anti-inflammatory actions of glucocorticoids (GCs). Viral infection elicits transforming growth factor-β (TGF-β) activity, a growth factor we have previously shown to impair GC action in human airway epithelial cells through the activation of activin-like kinase 5 (ALK5), the type 1 receptor of TGF-β. In the current study, we examine the contribution of TGF-β activity to the GC-resistance caused by viral infection. We demonstrate that viral infection of human bronchial epithelial cells with RSV, RV or IAV impairs GC anti-inflammatory action. Poly(I:C), a synthetic analog of double-stranded RNA, also impairs GC activity. Both viral infection and poly(I:C) increase TGF-β expression and activity. Importantly, the GC impairment was attenuated by the selective ALK5 (TGFβRI) inhibitor, SB431542 and prevented by the therapeutic agent, tranilast, which reduced TGF-β activity associated with viral infection. This study shows for the first time that viral-induced glucocorticoid-insensitivity is partially mediated by activation of endogenous TGF-β. PMID:28046097

  3. Infections in hemodialysis: a concise review. Part II: blood transmitted viral infections

    OpenAIRE

    2011-01-01

    Hemodialysis (HD) patients are particularly predisposed to infections. It seems that the HD procedure per se as well as disturbances in both innate and adaptive immunity significantly contribute to this susceptibility. Infections are the major cause of morbidity and the second cause of death following cardiovascular events in HD patients. Episodes of bacteremia and pneumonia account for the majority of severe infections in this population. In addition to these bacterial infections another com...

  4. Congenital viral infections of the brain: lessons learned from lymphocytic choriomeningitis virus in the neonatal rat.

    Directory of Open Access Journals (Sweden)

    Daniel J Bonthius

    2007-11-01

    Full Text Available 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

  5. Productive hepatitis C virus infection of stem cell-derived hepatocytes reveals a critical transition to viral permissiveness during differentiation.

    Directory of Open Access Journals (Sweden)

    Xianfang Wu

    Full Text Available Primary human hepatocytes isolated from patient biopsies represent the most physiologically relevant cell culture model for hepatitis C virus (HCV infection, but these primary cells are not readily accessible, display individual variability, and are largely refractory to genetic manipulation. Hepatocyte-like cells differentiated from pluripotent stem cells provide an attractive alternative as they not only overcome these shortcomings but can also provide an unlimited source of noncancer cells for both research and cell therapy. Despite its promise, the permissiveness to HCV infection of differentiated human hepatocyte-like cells (DHHs has not been explored. Here we report a novel infection model based on DHHs derived from human embryonic (hESCs and induced pluripotent stem cells (iPSCs. DHHs generated in chemically defined media under feeder-free conditions were subjected to infection by both HCV derived in cell culture (HCVcc and patient-derived virus (HCVser. Pluripotent stem cells and definitive endoderm were not permissive for HCV infection whereas hepatic progenitor cells were persistently infected and secreted infectious particles into culture medium. Permissiveness to infection was correlated with induction of the liver-specific microRNA-122 and modulation of cellular factors that affect HCV replication. RNA interference directed toward essential cellular cofactors in stem cells resulted in HCV-resistant hepatocyte-like cells after differentiation. The ability to infect cultured cells directly with HCV patient serum, to study defined stages of viral permissiveness, and to produce genetically modified cells with desired phenotypes all have broad significance for host-pathogen interactions and cell therapy.

  6. A multi-scale mathematical modeling framework to investigate anti-viral therapeutic opportunities in targeting HIV-1 accessory proteins.

    Science.gov (United States)

    Suryawanshi, Gajendra W; Hoffmann, Alexander

    2015-12-07

    Human immunodeficiency virus-1 (HIV-1) employs accessory proteins to evade innate immune responses by neutralizing the anti-viral activity of host restriction factors. Apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, A3G) and bone marrow stromal cell antigen 2 (BST2) are host resistance factors that potentially inhibit HIV-1 infection. BST2 reduces viral production by tethering budding HIV-1 particles to virus producing cells, while A3G inhibits the reverse transcription (RT) process and induces viral genome hypermutation through cytidine deamination, generating fewer replication competent progeny virus. Two HIV-1 proteins counter these cellular restriction factors: Vpu, which reduces surface BST2, and Vif, which degrades cellular A3G. The contest between these host and viral proteins influences whether HIV-1 infection is established and progresses towards AIDS. In this work, we present an age-structured multi-scale viral dynamics model of in vivo HIV-1 infection. We integrated the intracellular dynamics of anti-viral activity of the host factors and their neutralization by HIV-1 accessory proteins into the virus/cell population dynamics model. We calculate the basic reproductive ratio (Ro) as a function of host-viral protein interaction coefficients, and numerically simulated the multi-scale model to understand HIV-1 dynamics following host factor-induced perturbations. We found that reducing the influence of Vpu triggers a drop in Ro, revealing the impact of BST2 on viral infection control. Reducing Vif׳s effect reveals the restrictive efficacy of A3G in blocking RT and in inducing lethal hypermutations, however, neither of these factors alone is sufficient to fully restrict HIV-1 infection. Interestingly, our model further predicts that BST2 and A3G function synergistically, and delineates their relative contribution in limiting HIV-1 infection and disease progression. We provide a robust modeling framework for devising novel combination therapies that target

  7. Early immune responses in rainbow trout liver upon viral hemorrhagic septicemia virus (VHSV) infection.

    Science.gov (United States)

    Castro, Rosario; Abós, Beatriz; Pignatelli, Jaime; von Gersdorff Jørgensen, Louise; González Granja, Aitor; Buchmann, Kurt; Tafalla, Carolina

    2014-01-01

    Among the essential metabolic functions of the liver, in mammals, a role as mediator of systemic and local innate immunity has also been reported. Although the presence of an important leukocyte population in mammalian liver is well documented, the characterization of leukocyte populations in the teleost liver has been only scarcely addressed. In the current work, we have confirmed the presence of IgM+, IgD+, IgT+, CD8α+, CD3+ cells, and cells expressing major histocompatibility complex (MHC-II) in rainbow trout (Oncorhynchus mykiss) liver by flow cytometry and/or immunohistochemistry analysis. Additionally, the effect of viral hemorrhagic septicemia virus (VHSV) on the liver immune response was assessed. First, we studied the effect of viral intraperitoneal injection on the transcription of a wide selection of immune genes at days 1, 2 and 5 post-infection. These included a group of leukocyte markers genes, pattern recognition receptors (PRRs), chemokines, chemokine receptor genes, and other genes involved in the early immune response and in acute phase reaction. Our results indicate that T lymphocytes play a key role in the initial response to VHSV in the liver, since CD3, CD8, CD4, perforin, Mx and interferon (IFN) transcription levels were up-regulated in response to VHSV. Consequently, flow cytometry analysis of CD8α+ cells in liver and spleen at day 5 post-infection revealed a decrease in the number of CD8α+ cells in the spleen and an increased population in the liver. No differences were found however in the percentages of B lymphocyte (IgM+ or IgD+) populations. In addition, a strong up-regulation in the transcription levels of several PRRs and chemokines was observed from the second day of infection, indicating an important role of these factors in the response of the liver to viral infections.

  8. Early immune responses in rainbow trout liver upon viral hemorrhagic septicemia virus (VHSV infection.

    Directory of Open Access Journals (Sweden)

    Rosario Castro

    Full Text Available Among the essential metabolic functions of the liver, in mammals, a role as mediator of systemic and local innate immunity has also been reported. Although the presence of an important leukocyte population in mammalian liver is well documented, the characterization of leukocyte populations in the teleost liver has been only scarcely addressed. In the current work, we have confirmed the presence of IgM+, IgD+, IgT+, CD8α+, CD3+ cells, and cells expressing major histocompatibility complex (MHC-II in rainbow trout (Oncorhynchus mykiss liver by flow cytometry and/or immunohistochemistry analysis. Additionally, the effect of viral hemorrhagic septicemia virus (VHSV on the liver immune response was assessed. First, we studied the effect of viral intraperitoneal injection on the transcription of a wide selection of immune genes at days 1, 2 and 5 post-infection. These included a group of leukocyte markers genes, pattern recognition receptors (PRRs, chemokines, chemokine receptor genes, and other genes involved in the early immune response and in acute phase reaction. Our results indicate that T lymphocytes play a key role in the initial response to VHSV in the liver, since CD3, CD8, CD4, perforin, Mx and interferon (IFN transcription levels were up-regulated in response to VHSV. Consequently, flow cytometry analysis of CD8α+ cells in liver and spleen at day 5 post-infection revealed a decrease in the number of CD8α+ cells in the spleen and an increased population in the liver. No differences were found however in the percentages of B lymphocyte (IgM+ or IgD+ populations. In addition, a strong up-regulation in the transcription levels of several PRRs and chemokines was observed from the second day of infection, indicating an important role of these factors in the response of the liver to viral infections.

  9. The Effect of Childhood Viral Infections on the Incidence of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Reza Vazirinejad

    2013-02-01

    Full Text Available Background: In this study, the history of viral infections of measles, chickenpox and mumps in childhood was compared between the two groups of adults with multiple sclerosis (MS and healthy people. Materials and Methods: In this case-control study, a group of 45 MS patients and a group of 135 healthy people who were similar based on some variables were invited. Patients had a definite diagnosis of MS and control group consisted of people accompanying MS patients. Data were collected by a trained expert in face-to-face interview sessions. For data analysis, odds ratio index was calculated and 95% confidence interval was also computed. The mean age of respondents at the time of viral infections was also compared between the two groups.Results: The proportions of infected people by measles, chickenpox and mumps among MS patients were 58%, 56% and 40%, respectively. These proportions in healthy group were 68%, 52% and 44%, respectively. There was not any significant difference between these proportions in the two groups. Mean age of morbidity for measles, chickenpox and mumps among patients were 6.8±3.1, 8.7±2.98 and 10.6±4.7 years, and were significantly higher that these mean ages (4.1±2.1, 5.3±3.1 and 8.4±2.8, respectively among healthy people (p<0.001.Conclusion: Although there was not any significant difference between the history of morbidity of measles, chickenpox and mumps in the two groups of MS patients and healthy people, the mean ages of these viral infections among MS patients were significantly higher than healthy people.

  10. Viral infection of human progenitor and liver-derived cells encapsulated in three-dimensional PEG-based hydrogel

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nam-Joon; Elazar, Menashe; Xiong, Anming; Glenn, Jeffrey S [Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, CCSR Building Room 3115A, 269 Campus Drive, Stanford, CA 94305 (United States); Lee, Wonjae [Mechanical Engineering, Stanford University, Stanford, CA 94305 (United States); Chiao, Eric; Baker, Julie [Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305 (United States); Frank, Curtis W, E-mail: jeffrey.glenn@stanford.ed, E-mail: curt.frank@stanford.ed [Department of Chemical Engineering, Stanford University, Stanford, CA 94305 (United States)

    2009-02-15

    We have studied the encapsulation of human progenitor cells into 3D PEG hydrogels. Replication-incompetent lentivirus promoter reporter vectors were found to efficiently detect the in vivo expression of human hepatic genes in hydrogel-encapsulated liver progenitor cells. Similarly, hydrogel-encapsulated cells could be efficiently infected with hepatitis C virus, and progeny infectious virus could be recovered from the media supernatants of the hydrogels. Provocatively, the diameters of these virus particles range from {approx}50 to 100 nm, while the calculated mesh size of the 8 k hydrogel is 44.6 +- 1.7 A. To reconcile how viral particles can penetrate the hydrogels to infect the encapsulated cells, we propose that microfractures/defects of the hydrogel result in a functional pore size of up to 20 fold greater than predicted by theoretical mesh calculations. These results suggest a new model of hydrogel structure, and have exciting implications for tissue engineering and hepatitis virus studies. (communication)

  11. Relationship between common viral upper respiratory tract infections and febrile seizures in children from Suzhou, China.

    Science.gov (United States)

    Tang, Jihong; Yan, Wenhua; Li, Yan; Zhang, Bingbing; Gu, Qing

    2014-10-01

    This study aimed to determine the potential predisposing factors for the development of febrile seizures among children with upper respiratory tract infection in the eastern Chinese region. Participants were individuals aged 6 months and 6 years (n = 189) who were diagnosed with febrile seizure, complicated with upper respiratory tract infection, and 174 age-matched children who had upper respiratory tract infection without seizures as controls. The viral antigens including influenza A and B, parainfluenza, adenovirus, and respiratory syncytial virus were detected from nasopharyngeal aspirates. The incidence of influenza A infection was much higher in patients with febrile seizure than controls, especially those children aged >36 months. Patients with influenza A infection had higher body temperatures at seizure occurrence, shorter seizure duration, and shorter fever duration before seizure onset. Influenza A infections are frequently associated with febrile seizure in children with upper respiratory tract infection. During an influenza epidemic, effective vaccination of children, especially those with a past history of febrile seizure, may minimize the development of febrile seizure. © The Author(s) 2014.

  12. Efficient Reverse Genetics Reveals Genetic Determinants of Budding and Fusogenic Differences between Nipah and Hendra Viruses and Enables Real-Time Monitoring of Viral Spread in Small Animal Models of Henipavirus Infection

    Science.gov (United States)

    Yun, Tatyana; Park, Arnold; Hill, Terence E.; Pernet, Olivier; Beaty, Shannon M.; Juelich, Terry L.; Smith, Jennifer K.; Zhang, Lihong; Wang, Yao E.; Vigant, Frederic; Gao, Junling; Wu, Ping

    2014-01-01

    ABSTRACT Nipah virus (NiV) and Hendra virus (HeV) are closely related henipaviruses of the Paramyxovirinae. Spillover from their fruit bat reservoirs can cause severe disease in humans and livestock. Despite their high sequence similarity, NiV and HeV exhibit apparent differences in receptor and tissue tropism, envelope-mediated fusogenicity, replicative fitness, and other pathophysiologic manifestations. To investigate the molecular basis for these differences, we first established a highly efficient reverse genetics system that increased rescue titers by ≥3 log units, which offset the difficulty of generating multiple recombinants under constraining biosafety level 4 (BSL-4) conditions. We then replaced, singly and in combination, the matrix (M), fusion (F), and attachment glycoprotein (G) genes in mCherry-expressing recombinant NiV (rNiV) with their HeV counterparts. These chimeric but isogenic rNiVs replicated well in primary human endothelial and neuronal cells, indicating efficient heterotypic complementation. The determinants of budding efficiency, fusogenicity, and replicative fitness were dissociable: HeV-M budded more efficiently than NiV-M, accounting for the higher replicative titers of HeV-M-bearing chimeras at early times, while the enhanced fusogenicity of NiV-G-bearing chimeras did not correlate with increased replicative fitness. Furthermore, to facilitate spatiotemporal studies on henipavirus pathogenesis, we generated a firefly luciferase-expressing NiV and monitored virus replication and spread in infected interferon alpha/beta receptor knockout mice via bioluminescence imaging. While intraperitoneal inoculation resulted in neuroinvasion following systemic spread and replication in the respiratory tract, intranasal inoculation resulted in confined spread to regions corresponding to olfactory bulbs and salivary glands before subsequent neuroinvasion. This optimized henipavirus reverse genetics system will facilitate future investigations into

  13. [Autochthonous acute viral and bacterial infections of the central nervous system (meningitis and encephalitis)].

    Science.gov (United States)

    Pérez-Ruiz, Mercedes; Vicente, Diego; Navarro-Marí, José María

    2008-07-01

    Rapid diagnosis of acute viral and bacterial infections of the central nervous system (meningitis and encephalitis) is highly important for the clinical management of the patient and helps to establish early therapy that may solve life-threatening situations, to avoid unnecessary empirical treatments, to reduce hospital stay, and to facilitate appropriate interventions in the context of public health. Molecular techniques, especially real-time polymerase chain reaction, have become the fastest and most sensitive diagnostic procedures for autochthonous viral meningitis and encephalitis, and their role is becoming increasingly important for the diagnosis and control of most frequent acute bacterial meningitides. Automatic and closed systems may encourage the widespread and systematic use of molecular techniques for the diagnosis of these neurological syndromes in most laboratories.

  14. Treatment of extrahepatic manifestations of chronic hepatitis C viral infection--a challenge.

    Science.gov (United States)

    Tănăsescu, C; Ionescu, R

    2010-01-01

    Often, chronic hepatitis C infection is clinically manifested as extra hepatic disease. Therapy of the extra hepatic manifestations (EHM) is always difficult and based on the optimal and individual association of antiviral treatment, immunosuppressant and plasma cleaning techniques. We observed for 4 years 246 patients admitted to "Colentina" Internal Medicine Clinic, of whom 168 were diagnosed as chronic C hepatitis. 130 of those patients have had at least one EHM. In our experience, the presence of an EHM is significantly correlated with lack of early viral response and sustained viral response, as well. Cryoglobulinemic vasculitis needs to be treated with oral or pulse corticotherapy associated to plasmapheresis. When present, peripheral neuropathy and cryocrit greater than 10% are indicators of need of more than 3 plasmapheresis sessions.

  15. Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses

    OpenAIRE

    Pawelek, Kasia A.; Huynh, Giao T; Michelle Quinlivan; Ann Cullinane; Libin Rong; Perelson, Alan S.

    2012-01-01

    Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, ...

  16. Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections.

    Science.gov (United States)

    Stenglein, Mark D; Jacobson, Elliott R; Chang, Li-Wen; Sanders, Chris; Hawkins, Michelle G; Guzman, David S-M; Drazenovich, Tracy; Dunker, Freeland; Kamaka, Elizabeth K; Fisher, Debbie; Reavill, Drury R; Meola, Linda F; Levens, Gregory; DeRisi, Joseph L

    2015-05-01

    Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology

  17. Oxidative stress in severe dengue viral infection: association of thrombocytopenia with lipid peroxidation.

    Science.gov (United States)

    Soundravally, R; Sankar, P; Bobby, Z; Hoti, S L

    2008-09-01

    Oxidative stress in viral infections has been suggested. The study was carried out to assess the oxidative stress in the different clinical spectrums of dengue infection and to evaluate if thrombocytopenia is associated with lipid and protein oxidative injury. Twenty-seven dengue fever (DF), 32 dengue hemorrhagic fever (DHF) and 21 dengue shock syndrome (DSS) cases were studied at 3, 5 and 7 days of illness. Sixty-three healthy subjects were selected as controls. Serum protein carbonyls (PCOs), malendialdehyde (MDA) and total antioxidant status (TAS) were estimated in blood. Dengue infected individuals had significantly high levels of PCOs and MDA on the three days tested in comparison to controls. In DF cases, no significant changes in the levels of MDA and PCOs were found in course of time. However, among DHF and DSS, significant increase in MDA levels was found in the fifth and seventh day samples in comparison to their respective third day sample (P platelet count and plasma lipid peroxidation levels among DHF and DSS on all three days tested [day 3 (DHF r = -0.392; p = 0.012 and DSS r = -0.453; p = 0.004), day 5 (DHF r = -0.592; p viral infection. The level of oxidative stress was maximal in DSS followed by DHF and its severity was minimal in DF. The thrombocytopenia of dengue infection was associated with the extent of lipid peroxidation. Future studies might be carried out to find the role of oxidative damage in the ethiopathogenesis of thrombocytopenia and vascular leakage in dengue infection.

  18. Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections.

    Directory of Open Access Journals (Sweden)

    Mark D Stenglein

    2015-05-01

    Full Text Available Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L and small (S genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on

  19. Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques

    Directory of Open Access Journals (Sweden)

    Marx Preston

    2006-12-01

    Full Text Available Abstract Background Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1 is a major obstacle to successful antiretroviral therapy (ART in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (SIV. Rhesus macaques infected with live, attenuated SIV develop robust SIV-specific immune responses but remain viremic, often at low levels, for periods of months to years, thus providing a model in which to evaluate the contribution of antiviral immunity to drug efficacy. To investigate the extent to which SIV-specific immune responses augment suppression of drug-resistant SIV, rhesus macaques infected with live, attenuated SIVmac239Δnef were treated with the reverse transcriptase (RT inhibitor tenofovir, and then challenged with pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir. Results Replication of SIVmac055 was detected in untreated macaques infected with SIVmac239Δnef, and in tenofovir-treated, naïve control macaques. The majority of macaques infected with SIVmac055 experienced high levels of plasma viremia, rapid CD4+ T cell loss and clinical disease progression. By comparison, macaques infected with SIVmac239Δnef and treated with tenofovir showed no evidence of replicating SIVmac055 in plasma using allele-specific real-time PCR assays with a limit of sensitivity of 50 SIV RNA copies/ml plasma. These animals remained clinically healthy with stable CD4+ T cell counts during three years of follow-up. Both the tenofovir-treated and untreated macaques infected with SIVmac239Δnef had antibody responses to SIV gp130 and p27 antigens and SIV-specific CD8+ T cell responses prior to SIVmac055 challenge, but only those animals receiving concurrent treatment with tenofovir resisted infection with SIVmac055. Conclusion

  20. Cognitive change trajectories in virally suppressed HIV-infected individuals indicate high prevalence of disease activity

    Science.gov (United States)

    Gott, Chloe; Gates, Thomas; Dermody, Nadene; Brew, Bruce J.

    2017-01-01

    Background The longitudinal rate and profile of cognitive decline in persons with stable, treated, and virally suppressed HIV infection is not established. To address this question, the current study quantifies the rate of cognitive decline in a cohort of virally suppressed HIV+ persons using clinically relevant definitions of decline, and determine cognitive trajectories taking into account historical and baseline HAND status. Methods Ninety-six HIV+ (clinically stable and virally undetectable) and 44 demographically comparable HIV- participants underwent standard neuropsychological testing at baseline and 18-months follow-up. We described clinically relevant cognitive trajectories based on standard definitions of historical and baseline HAND status and cognitive decline. Historical, moderate to severe HAND was formally diagnosed at the start of the cART era in 15/96 participants based on clinical neurological and neuropsychological assessment. The same standard of care has been applied to all participants at St. Vincent’s Hospital Infectious Disease Department for the duration of their HIV infection (median of 20 years). Results Relative to HIV- controls (4.5%), 14% of HIV+ participants declined (p = .11), they also scored significantly lower on the global change score (p = .03), processing speed (p = .02), and mental flexibility/inhibition (p = .02) domains. Having HAND at baseline significantly predicted cognitive decline at follow up (p = .005). We determined seven clinically relevant cognitive trajectories taking into account whether participant has a history of HAND prior to study entry (yes/no); their results on the baseline assessment (baseline impairment: yes/no) and their results on the 18-month follow up (decline or stable) which in order of prevalence were: 1) No HAND history, no baseline impairment, 18-month follow-up stable (39%), 2) No HAND history, baseline impairment, 18-month follow-up stable (35%), 3) History of HAND; baseline impairment, 18

  1. Experimental infection of Newcastle disease virus in pigeons (Columba livia): humoral antibody response, contact transmission and viral genome shedding.

    Science.gov (United States)

    de Oliveira Torres Carrasco, Adriano; Seki, Meire Christina; de Freitas Raso, Tânia; Paulillo, Antônio Carlos; Pinto, Aramis Augusto

    2008-05-25

    The aim of this study was to evaluate the humoral antibody response, the genome viral excretion and the contact transmission of pathogenic chicken origin Newcastle disease virus (NDV) from experimentally infected pigeons (Columba livia) to in-contact pigeon. The antibody response to infection was assessed by the hemagglutination inhibition (HI) test and the genome viral excretion was detected by RT-PCR. Viral strain induced high antibody levels, both in inoculated and in sentinel birds. The pathogenic viral strain for chickens was unable to produce clinical signs of the disease in experimentally infected pigeons, although it induced the humoral antibody response and produced NDV genome shedding. NDV genome was detected intermittently throughout the experimental period, from 5 days post-infection (dpi) to 24 dpi. Therefore, viral genome shedding occurred for 20 days. The viral genome was detected in all birds, between 11 and 13 dpi. Furthermore, the high infectivity of the virus was confirmed, as all non-inoculated sentinel pigeons showed antibody levels as high as those of inoculated birds.

  2. Early regulation of viral infection reduces inflammation and rescues mx-positive mice from lethal avian influenza infection.

    Science.gov (United States)

    Song, Min-Suk; Cho, Young-Hun; Park, Su-Jin; Pascua, Philippe Noriel Q; Baek, Yun Hee; Kwon, Hyeok-Il; Lee, Ok-Jun; Kong, Byung-Whi; Kim, Hyunggee; Shin, Eui-Cheol; Kim, Chul-Joong; Choi, Young Ki

    2013-04-01

    Differing sensitivity of influenza A viruses to antiviral effects of the Myxovirus resistance (Mx) protein implies varying global gene expression profiles in the host. The role of Mx protein during lethal avian influenza (AI) virus infection was examined using Mx1-deficient C57BL/6 (B6-Mx1(-/-)) and congenic Mx1-expressing (B6-Mx1(+/+)) mice infected with a virulent, mouse-adapted avian H5N2 Ab/Korea/ma81/07 (Av/ma81) virus. After infection, B6-Mx1(+/+) mice were completely protected from lethal AI-induced mortality, and exhibited attenuated clinical disease and reduced viral titers and pathology in the lungs, compared with B6-Mx1(-/-) mice. Transcriptional profiling of lung tissues revealed that most of the genes up-regulated after infection are involved in activation of the immune response and host defense. Notably, more abundant and sustained expression of cytokine/chemokine genes was observed up to 3 dpi in B6-Mx1(-/-) mice, and this was associated with excessive induction of cytokines and chemokines. Consequently, massive infiltration of macrophages/monocytes and granulocytes into lung resulted in severe viral pneumonia and potentially contributed to decreased survival of B6-Mx1(-/-) mice. Taken together, our data show that dysregulated gene transcriptional activity corresponded to persistent induction of cytokine/chemokines and recruitment of cytokine-producing cells that promote inflammation in B6-Mx1(-/-) mouse lungs. Thus, we provide additional evidence of the interplay of genetic, molecular, and cellular correlates governed by the Mx1 protein that critically determine disease outcome during lethal AI virus infection.

  3. Direct TLR2 signaling is critical for NK cell activation and function in response to vaccinia viral infection.

    Directory of Open Access Journals (Sweden)

    Jennifer Martinez

    2010-03-01

    Full Text Available Natural killer (NK cells play an essential role in innate immune control of poxviral infections in vivo. However, the mechanism(s underlying NK cell activation and function in response to poxviruses remains poorly understood. In a mouse model of infection with vaccinia virus (VV, the most studied member of the poxvirus family, we identified that the Toll-like receptor (TLR 2-myeloid differentiating factor 88 (MyD88 pathway was critical for the activation of NK cells and the control of VV infection in vivo. We further showed that TLR2 signaling on NK cells, but not on accessory cells such as dendritic cells (DCs, was necessary for NK cell activation and that this intrinsic TLR2-MyD88 signaling pathway was required for NK cell activation and played a critical role in the control of VV infection in vivo. In addition, we showed that the activating receptor NKG2D was also important for efficient NK activation and function, as well as recognition of VV-infected targets. We further demonstrated that VV could directly activate NK cells via TLR2 in the presence of cytokines in vitro and TLR2-MyD88-dependent activation of NK cells by VV was mediated through the phosphatidylinositol 3-kinase (PI3K-extracellular signal-regulated kinase (ERK pathway. Taken together, these results represent the first evidence that intrinsic TLR signaling is critical for NK cell activation and function in the control of a viral infection in vivo, indicate that multiple pathways are required for efficient NK cell activation and function in response to VV infection, and may provide important insights into the design of effective strategies to combat poxviral infections.

  4. A comprehensive collection of systems biology data characterizing the host response to viral infection.

    Science.gov (United States)

    Aevermann, Brian D; Pickett, Brett E; Kumar, Sanjeev; Klem, Edward B; Agnihothram, Sudhakar; Askovich, Peter S; Bankhead, Armand; Bolles, Meagen; Carter, Victoria; Chang, Jean; Clauss, Therese R W; Dash, Pradyot; Diercks, Alan H; Eisfeld, Amie J; Ellis, Amy; Fan, Shufang; Ferris, Martin T; Gralinski, Lisa E; Green, Richard R; Gritsenko, Marina A; Hatta, Masato; Heegel, Robert A; Jacobs, Jon M; Jeng, Sophia; Josset, Laurence; Kaiser, Shari M; Kelly, Sara; Law, G Lynn; Li, Chengjun; Li, Jiangning; Long, Casey; Luna, Maria L; Matzke, Melissa; McDermott, Jason; Menachery, Vineet; Metz, Thomas O; Mitchell, Hugh; Monroe, Matthew E; Navarro, Garnet; Neumann, Gabriele; Podyminogin, Rebecca L; Purvine, Samuel O; Rosenberger, Carrie M; Sanders, Catherine J; Schepmoes, Athena A; Shukla, Anil K; Sims, Amy; Sova, Pavel; Tam, Vincent C; Tchitchek, Nicolas; Thomas, Paul G; Tilton, Susan C; Totura, Allison; Wang, Jing; Webb-Robertson, Bobbie-Jo; Wen, Ji; Weiss, Jeffrey M; Yang, Feng; Yount, Boyd; Zhang, Qibin; McWeeney, Shannon; Smith, Richard D; Waters, Katrina M; Kawaoka, Yoshihiro; Baric, Ralph; Aderem, Alan; Katze, Michael G; Scheuermann, Richard H

    2014-01-01

    The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). By comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.

  5. The role of viral infection in the development of severe drug eruptions

    Directory of Open Access Journals (Sweden)

    Tetsuo Shiohara

    2013-12-01

    Full Text Available The role of viral infections in the development of drug allergy has recently received increasing attention. Evidence is accumulating that immune responses to drugs can be profoundly influenced by herpesvirus infection that occurs before, concurrent with, or subsequent to drug administration. The current advances in our understanding of the role of viral infections in drug eruptions have been sparked by recent studies on human herpesvirus 6 (HHV-6 reactivation in severe systemic hypersensitivity reactions to drugs, eventually referred to as drug-induced hypersensitivity syndrome (DiHS/drug reaction with eosinophilia with systemic symptoms (DRESS. It becomes clear that HHV-6 is not the only herpes virus reactivated during the course of DiHS and other herpes viruses are also reactivated in sequence as shown in graft-versus-host disease (GVHD, which can explain frequent deterioration or several flare-ups of clinical symptoms occurring after withdrawal of the causative drug in DiHS. Here we describe how sequential reactivations of herpesviruses occur during the course of DiHS and discuss how the reactivation events could influence the initiation and maintenance of drug-specific immune responses, resulting in severe immunopathology.

  6. HIV taken by STORM: Super-resolution fluorescence microscopy of a viral infection

    Directory of Open Access Journals (Sweden)

    Pereira Cândida F

    2012-05-01

    Full Text Available Abstract Background The visualization of viral proteins has been hindered by the resolution limit of conventional fluorescent microscopes, as the dimension of any single fluorescent signal is often greater than most virion particles. Super-resolution microscopy has the potential to unveil the distribution of proteins at the resolution approaching electron microscopy without relying on morphological features of existing characteristics of the biological specimen that are needed in EM. Results Using direct stochastic optical reconstruction microscopy (dSTORM to achieve a lateral resolution of 15–20 nm, we quantified the 2-D molecular distribution of the major structural proteins of the infectious human immunodeficiency virus type 1 (HIV-1 before and after infection of lymphoid cells. We determined that the HIV-1 matrix and capsid proteins undergo restructuring soon after HIV-1 infection. Conclusions This study provides the proof-of-concept for the use of dSTORM to visualize the changes in the molecular distribution of viral proteins during an infection.

  7. Microarray analysis of gene expression in olive flounder liver infected with viral haemorrhagic septicaemia virus (VHSV).

    Science.gov (United States)

    Cho, Hyun Kook; Kim, Julan; Moon, Ji Young; Nam, Bo-Hye; Kim, Young-Ok; Kim, Woo-Jin; Park, Jung Youn; An, Cheul Min; Cheong, Jaehun; Kong, Hee Jeong

    2016-02-01

    The most fatal viral pathogen in olive flounder Paralichthys olivaceus, is viral hemorrhagic septicemia virus, which afflicts over 48 species of freshwater and marine fish. Here, we performed gene expression profiling on transcripts isolated from VHSV-infected olive flounder livers using a 13 K cDNA microarray chip. A total of 1832 and 1647 genes were upregulated and down-regulated over two-fold, respectively, after infection. A variety of immune-related genes showing significant changes in gene expression were identified in upregulated genes through gene ontology annotation. These genes were grouped into categories such as antibacterial peptide, antigen-recognition and adhesion molecules, apoptosis, cytokine-related pathway, immune system, stress response, and transcription factor and regulatory factors. To verify the cDNA microarray data, we performed quantitative real-time PCR, and the results were similar to the microarray data. In conclusion, these results may be useful for the identification of specific genes or for the diagnosis of VHSV infection in flounder.

  8. Evaluation of viral load in saliva from patients with chronic hepatitis C infection.

    Science.gov (United States)

    Xavier Santos, Renata L; de Deus, Dayse M V; de Almeida Lopes, Edmundo P; Duarte Coêlho, Maria R C; de Castro, Jurema F L

    2015-01-01

    Hepatitis C virus can be detected in blood and other bodily fluids, such as saliva. The aim of this study was to detect and quantify the HCV-RNA in saliva and plasma from patients with chronic hepatitis C infections, as well as check the level of viral load in sex groups (age, ethnicity and virus subtypes). Whole saliva and blood from 70 patients with chronic hepatitis C infections attended at the department of gastroenterology from University Hospital. The HCV-RNA load was performed by qRT-PCR using Sybr Green I master mix. HCV-RNA was detected in 80% (56/70) of patients in saliva and 92.85% (65/70) in plasma. The median of the viral load in the plasma was of 4.87 log10, and in saliva, it was 3.32log10, (p = 0.0005). Female patients and black patients exhibited a negative correlation between the HCV-RNA load in saliva vs. the HCV-RNA load in plasma (r = -0.3172, CI95% -0.6240 to -0.03736, p = 0.0491) and (r = -0.3141; IC95% -0.6069 to -0.05926; p = 0.0209), respectively. HCV-RNA was detected and quantified in saliva samples, and according to the quantification levels, saliva may be a possible transmission source of HCV, particularly in women and people of black ethnicity who develop chronic HCV infections.

  9. Detection of Viral RNA in Tissues following Plasma Clearance from an Ebola Virus Infected Patient

    Science.gov (United States)

    Bordi, Licia; Castilletti, Concetta; Colavita, Francesca; Quartu, Serena; Nicastri, Emanuele; Lauria, Francesco Nicola; Petrosillo, Nicola; Lanini, Simone; Kobinger, Gary; Zumla, Alimuddin; Di Caro, Antonino; Ippolito, Giuseppe; Capobianchi, Maria Rosaria; Lalle, Eleonora

    2017-01-01

    An unprecedented Ebola virus (EBOV) epidemic occurred in 2013–2016 in West Africa. Over this time the epidemic exponentially grew and moved to Europe and North America, with several imported cases and many Health Care Workers (HCW) infected. Better understanding of EBOV infection patterns in different body compartments is mandatory to develop new countermeasures, as well as to fully comprehend the pathways of human-to-human transmission. We have longitudinally explored the persistence of EBOV-specific negative sense genomic RNA (neg-RNA) and the presence of positive sense RNA (pos-RNA), including both replication intermediate (antigenomic-RNA) and messenger RNA (mRNA) molecules, in the upper and lower respiratory tract, as compared to plasma, in a HCW infected with EBOV in Sierra Leone, who was hospitalized in the high isolation facility of the National Institute for Infectious Diseases “Lazzaro Spallanzani” (INMI), Rome, Italy. We observed persistence of pos-RNA and neg-RNAs in longitudinally collected specimens of the lower respiratory tract, even after viral clearance from plasma, suggesting possible local replication. The purpose of the present study is to enhance the knowledge on the biological features of EBOV that can contribute to the human-to-human transmissibility and to develop effective intervention strategies. However, further investigation is needed in order to better understand the clinical meaning of viral replication and shedding in the respiratory tract. PMID:28056096

  10. Management of Viral Central Nervous System Infections: A Primer for Clinicians

    Directory of Open Access Journals (Sweden)

    P Brandon Bookstaver

    2017-04-01

    Full Text Available Viruses are a common cause of central nervous system (CNS infections with many host, agent, and environmental factors influencing the expression of viral diseases. Viruses can be responsible for CNS disease through a variety of mechanisms including direct infection and replication within the CNS resulting in encephalitis, infection limited to the meninges, or immune-related processes such as acute disseminated encephalomyelitis. Common pathogens including herpes simplex virus, varicella zoster, and enterovirus are responsible for the greatest number of cases in immunocompetent hosts. Other herpes viruses (eg, cytomegalovirus, John Cunningham virus are more common in immunocompromised hosts. Arboviruses such as Japanese encephalitis virus and Zika virus are important pathogens globally, but the prevalence varies significantly by geographic region and often season. Early diagnosis from radiographic evidence and molecular (eg, rapid diagnostics is important for targeted therapy. Antivirals may be used effectively against some pathogens, although several viruses have no effective treatment. This article provides a review of epidemiology, diagnostics, and management of common viral pathogens in CNS disease.

  11. [Micronutrients and tropical viral infections: one aspect of pathogenic complexity in tropical medicine].

    Science.gov (United States)

    Malvy, D

    1999-01-01

    In tropical zones, uncertain living conditions, inadequate food intake, and poor medical facilities enhance unnecessary morbidity and mortality especially involving infants and young children. In addition to protein-caloric malnutrition, deficiencies in essential micronutrients have a specific health impact. Such deficiencies can be the direct cause of disease such as vitamin A deficiency and blindness or have a promoting effect by compromising immune status and increasing susceptibility to and severity of infectious diseases especially of viral origin. The promoting effect of micronutrient deficiency plays a significant role in measles, rotavirus-related diarrhea, and, to a certain extent, progression of HIV infection. Several examples are described to illustrate the relationship between tropical viral infection and micronutrients including vitamin A, selenium, and various other antioxidants. These examples highlight the effect of infectious disease on micronutritional status (vitamin A and measles) and the need to develop reliable, practical tools to evaluate the relevance and effectiveness of dietary supplementation. In any case, improving living conditions and health programs such as the Expanded Vaccination Program are required and illustrate a transverse approach for prevention of infectious and non-infectious tropical disease. The relationship between micronutrients and infection is only one aspect of the multifactorial reality that must be dealt with in tropical medicine.

  12. Association between secondary thrombocytosis and viral respiratory tract infections in children.

    Science.gov (United States)

    Zheng, Shou-Yan; Xiao, Qiu-Yan; Xie, Xiao-Hong; Deng, Yu; Ren, Luo; Tian, Dai-Yin; Luo, Zheng-Xiu; Luo, Jian; Fu, Zhou; Huang, Ai-Long; Liu, En-Mei

    2016-03-11

    Secondary thrombocytosis (ST) is frequently observed in children with a variety of clinical conditions. The leading cause of ST is respiratory tract infection (RTI) in children. Nasopharyngeal aspirate samples were collected and assessed for common respiratory viruses. The relationships between virus infections and secondary thrombocytosis were analyzed retrospectively. The blood platelet count and the presence of respiratory viruses were determined for 3156 RTI patients, and 817 (25.9%) cases with platelet ≥500 × 10(9)/L were considered as the thrombocytosis group. Compared with the normal group, the detection rates of respiratory syncytial virus (RSV) and human rhinovirus (HRV) were significantly higher in the thrombocytosis group (P = 0.017 and 0.042, respectively). HRV single infection was a risk factor associated with thrombocytosis [odds ratio (OR) = 1.560, 95% confidence interval (CI) = 1.108-2.197]. Furthermore, ST was more likely to occur in younger patients who had clinical manifestations of wheezing and dyspnea and who had been diagnosed with bronchiolitis. Furthermore, the course of disease lasted longer in these patients. ST is associated with viral respiratory tract infections, especially RSV and HRV infections. HRV single infection is a risk factor associated with thrombocytosis.

  13. Some viral and bacterial respiratory tract infections of dairy cattle during the summer season

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    Kale M.

    2013-01-01

    Full Text Available In this research, dairy cattle with respiratory system problems that were brought to a private slaughterhouse in Burdur province were investigated for viral and bacterial infections present in the summer season. The blood samples were collected from 56 animals. The samples were tested for antibodies against bovine herpesvirus 1 (BoHV-1, bovine viral diarrhea virus (BVDV, bovine respiratory syncytial virus (BRSV, bovine parainfluenza virus 3 (BPIV-3 and bovine adenovirus 3 (BAV-3 by ELISA. Bacteriological cultivation was carried out from lung samples taken after cutting the same animals. The seropositivity rates which were determined for 5 viruses in cattle (BoHV- 1, BVDV, BRSV, BPIV-3 and BAV-3 were 7.14%, 50%, 94.64%, 94.64% and 82.14% respectively. The presence of antibodies against the viruses was as follows; 5.36% of cattle had antibodies against only one virus, 14.29% against two, 30.36% against three, 44.64% against four and 5.36% against five viruses. A total of 36 bacterial agents were isolated from 30 out of 56 lung samples. From the lung samples, only one bacterium was isolated from 39.3% (22/56 samples, and more than one bacterium from 14.3% (8/56. Escherichia coli, Staphylococcus aureus and Streptococcus spp. were detected as the most often isolated agents. Compared to bacteria, the rates of viral infections associated with Escherichia coli (BRSV+BPIV-3+BAV- 3+Escherichia coli; 8.92% and BRSV+BPIV-3+Escherichia coli; 5.35% were higher. As a consequence, it was thought that primary agents which were the viruses and bacteria may have attended as secondary factors in respiratory tract infections of dairy cattle.

  14. Viral infection-associated vasculitis%病毒相关血管炎

    Institute of Scientific and Technical Information of China (English)

    李志量; 靳培英; 冯素英

    2012-01-01

    Vasculitis refers to the inflammation of blood vessel walls and surrounding tissues.It can be divided into systemic vasculitis and cutaneous vasculitis according to the spectrum of involvement.The etiology of vaculitis is complex and viral infection is considered to be a cause of it.There has been increasing evidence for the association between hepatitis C virus and mixed cryoglobulinemia as well as between hepatitis B virus and polyarteritis nodosa.Epstein-barr virus and human immunodeficiency virus (HIV) can also induce vasculitis.Studies have confirmed the relationship between viral infection and cutaneous vasculitis.To recognize the relationship between viral infection and vasculitis is helpful for the diagnosis and therapy of vasculitis.%血管炎是指原发于血管壁及其周围组织的炎症变化,根据累及范围不同可分为系统性血管炎和皮肤血管炎.血管炎的病因复杂,研究表明,病毒感染是血管炎的致病原因之一,其中丙型肝炎病毒感染与原发性冷球蛋白血症、乙型肝炎病毒与结节性多动脉炎的相关性已被越来越多的研究证实,EB病毒、HIV病毒也可以诱发血管炎.有研究证明,很多皮肤血管炎与病毒感染有相关性.认识病毒感染与某些血管炎的相关性,有利于对血管炎发病机制的研究及指导临床血管炎的诊断和治疗.

  15. Anti-diabetic drugs, insulin and metformin, have no direct interaction with hepatitis C virus infection or anti-viral interferon response

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    Mohamad S. Hakim

    2014-01-01

    Full Text Available Hepatitis C virus (HCV infection is associated with insulin resistance (IR and type 2 diabetes (T2D. Chronic HCV patients with IR and T2D appear to have a decreased response to the standard pegylated-interferon-alpha and ribavirin (PEG-IFN/RBV anti-viral therapy. Insulin and metformin are anti-diabetic drugs regularly used in the clinic. A previous in vitro study has shown a negative effect of insulin on interferon signaling. In the clinic, adding metformin to PEG-IFN/RBV therapy was reported to increase the response rate in chronic HCV patients and it has been suggested this effect derives from an improved anti-viral action of interferon. The goal of this study was to further investigate the molecular insight of insulin and metformin interaction with HCV infection and the anti-viral action of interferon. We used two cell culture models of HCV infection. One is a sub-genomic model that assays viral replication through luciferase reporter gene expression. The other one is a full-length infectious model derived from the JFH1 genotype 2a isolate. We found that both insulin and metformin do not affect HCV infection. Insulin and metformin also do not influence the anti-viral potency of interferon. In addition, there is no direct interaction between these two drugs and interferon signaling. Our results do not confirm the previous laboratory observation that insulin interferes with interferon signaling and suggest that classical nutritional signaling through mTOR may be not involved in HCV replication. If metformin indeed can increase the response rate to interferon therapy in patients, our data indicate that this could be mediated via an indirect mechanisms.

  16. Active cAMP-dependent protein kinase incorporated within highly purified HIV-1 particles is required for viral infectivity and interacts with viral capsid protein.

    Science.gov (United States)

    Cartier, Christine; Hemonnot, Bénédicte; Gay, Bernard; Bardy, Martine; Sanchiz, Céline; Devaux, Christian; Briant, Laurence

    2003-09-12

    Host cell components, including protein kinases such as ERK-2/mitogen-activated protein kinase, incorporated within human immunodeficiency virus type 1 (HIV-1) virions play a pivotal role in the ability of HIV to infect and replicate in permissive cells. The present work provides evidence that the catalytic subunit of cAMP-dependent protein kinase (C-PKA) is packaged within HIV-1 virions as demonstrated using purified subtilisin-digested viral particles. Virus-associated C-PKA was shown to be enzymatically active and able to phosphorylate synthetic substrate in vitro. Suppression of virion-associated C-PKA activity by specific synthetic inhibitor had no apparent effect on viral precursor maturation and virus assembly. However, virus-associated C-PKA activity was demonstrated to regulate HIV-1 infectivity as assessed by single round infection assays performed by using viruses produced from cells expressing an inactive form of C-PKA. In addition, virus-associated C-PKA was found to co-precipitate with and to phosphorylate the CAp24gag protein. Altogether our results indicate that virus-associated C-PKA regulates HIV-1 infectivity, possibly by catalyzing phosphorylation of the viral CAp24gag protein.

  17. Isolation of a mutant MDBK cell line resistant to bovine viral diarrhea virus infection due to a block in viral entry.

    Science.gov (United States)

    Flores, E F; Donis, R O

    1995-04-20

    A cell line, termed CRIB, resistant to infection with bovine viral diarrhea virus (BVDV) has been derived from the MDBK bovine kidney cell line. CRIB cells were obtained by selection and cloning of cells surviving infection with a highly cytolytic BVDV strain. CRIB cells contain no detectable infectious or defective BVDV as ascertained by cocultivation, animal inoculation, indirect immunofluorescence, Western immunoblot, Northern hybridization, and RNA PCR. Inoculation of CRIB cells with 24 cytopathic and noncytopathic BVDV strains does not result in expression of viral genes or amplification of input virus. Karyotype and isoenzyme analyses demonstrated that CRIB are genuine bovine cells. CRIB cells are as susceptible as the parental MDBK cells to 10 other bovine viruses, indicating that these cells do not have a broad defect blocking viral replication. Transfection of CRIB cells with BVDV RNA or virus inoculation in the presence of polyethylene-glycol results in productive infection, indicating that the defect of CRIB cells is at the level of virus entry. CRIB cells are the first bovine cells reported to be resistant to BVDV infection in vitro and may be a useful tool for studying the early interactions of pestiviruses with host cells.

  18. Analysis of plasma viral RNA levels during acute dengue virus infection using quantitative competitor reverse transcription-polymerase chain reaction.

    Science.gov (United States)

    Sudiro, T M; Zivny, J; Ishiko, H; Green, S; Vaughn, D W; Kalayanarooj, S; Nisalak, A; Norman, J E; Ennis, F A; Rothman, A L

    2001-01-01

    There is increasing recognition of the potential importance of viral burden in the pathogenesis of dengue hemorrhagic fever (DHF). There is little data available, however, describing the kinetics of viral replication in humans with natural dengue virus (DV) infection. Standard procedures for measuring titers of infectious virus in clinical specimens are either laborious or insensitive. We developed a method for measurement of DV RNA in plasma samples based on reverse transcription-polymerase chain reaction (RT-PCR) using a mutant RNA target as a competitor. This technique was reproducible and accurate for samples containing any of the four DV serotypes, and could be applied to samples containing as few as 250 copies of RNA per reaction. We examined plasma viral RNA levels in 80 children with acute DV infection; sequential plasma samples were tested in 34 of these children. Plasma viral RNA levels ranged as high as 10(9) RNA copies/ml, and correlated with titers of infectious virus measured in mosquitoes (r= 0.69). Plasma viral RNA levels fell rapidly during the last several days of the febrile period. We did not find a significant difference in maximal plasma viral RNA levels between children with DHF and children with dengue fever, but peak viral RNA levels were identified in only 16 subjects. We conclude that this quantitative RT-PCR method will be valuable for further studies of natural DV infections.

  19. Bat Mx1 and Oas1, but not Pkr are highly induced by bat interferon and viral infection.

    Science.gov (United States)

    Zhou, Peng; Cowled, Christopher; Wang, Lin-Fa; Baker, Michelle L

    2013-01-01

    Bats harbour many emerging and re-emerging viruses, several of which are highly pathogenic in other mammals but cause no diseases in bats. As the interferon (IFN) response represents a first line of defence against viral infection, the ability of bats to control viral replication may be linked to the activation of the IFN system. The three most studied antiviral IFN-stimulated genes (ISGs) in other mammals; Pkr, Mx1 and Oas1 were examined in our model bat species, Pteropus alecto. Our results demonstrate that the three ISGs from P. alecto are highly conserved in their functional domains and promoter elements compared to corresponding genes from other mammals. However, P. alecto Oas1 contains two IFN-stimulated response elements (ISRE) in its promoter region compared with the single ISRE present in human OAS1 which may lead to higher IFN inducibility of the bat gene. Both Oas1 and Mx1 were induced in a highly IFN-dependent manner following stimulation with IFN or synthetic double-strand RNA (dsRNA) whereas Pkr showed evidence of being induced in an IFN-independent manner. Furthermore, bat Oas1 appeared to be the most inducible of the three ISGs following either IFN stimulation or viral infection, providing evidence that Oas1 may play a more important role in antiviral activity in bats compared with Mx1 or Pkr. Our results have important implications for the different roles of ISGs in bats and provide the first step in understanding the role of these molecules in the ability of bats to coexist with viruses.

  20. Multiple functions of DDX3 RNA helicase in gene regulation, tumorigenesis and viral infection

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    YASUO eARIUMI

    2014-12-01

    Full Text Available The DEAD-box RNA helicase DDX3 is a multifunctional protein involved in all aspects of RNA metabolism, including transcription, splicing, mRNA nuclear export, translation, RNA decay and ribosome biogenesis. In addition, DDX3 is also implicated in cell cycle regulation, apoptosis, Wnt-ß-catenin signaling, tumorigenesis, and viral infection. Notably, recent studies suggest that DDX3 is a component of anti-viral innate immune signaling pathways. Indeed, DDX3 contributes to enhance the induction of anti-viral mediators, interferon regulatory factor (IRF 3 and type I interferon (IFN. However, DDX3 seems to be an important target for several viruses, such as human immunodeficiency virus (HIV-1, hepatitis C virus (HCV, hepatitis B virus (HBV, and poxvirus. DDX3 interacts with HIV-1 Rev or HCV Core protein and modulates its function. At least, DDX3 is required for both HIV-1 and HCV replication. Therefore, DDX3 could be a novel therapeutic target for the development of drug against HIV-1 and HCV.