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Antiviral Immune Responses (antiviral + immune_response)
Selected AbstractsInhibition of CD1d1-mediated antigen presentation by the vaccinia virus B1R and H5R moleculesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2006Roberts Webb, Tonya Abstract Vaccinia virus (VV) has been most commonly used as the vaccine to protect individuals against the causative agent of smallpox (variola virus), but it also uses a number of strategies meant to evade or blunt the host's antiviral immune response. Natural killer T (NKT) cells are a subset of immunoregulatory CD1d-restricted T lymphocytes believed to bridge the innate and adaptive immune responses. It is shown here that the VV-encoded molecules, B1R and H5R, play a role in the ability of VV to inhibit CD1d-mediated antigen presentation to NKT cells. These are the first poxvirus-encoded molecules identified that can play such a role in the evasion of an important component of the innate immune response. [source] Pre-exposure to infectious hypodermal and haematopoietic necrosis virus or to inactivated white spot syndrome virus (WSSV) confers protection against WSSV in Penaeus vannamei (Boone) post-larvaeJOURNAL OF FISH DISEASES, Issue 10 2006J Melena Abstract Larvae and post-larvae of Penaeus vannamei (Boone) were submitted to primary challenge with infectious hypodermal and haematopoietic necrosis virus (IHHNV) or formalin-inactivated white spot syndrome virus (WSSV). Survival rate and viral load were evaluated after secondary per os challenge with WSSV at post-larval stage 45 (PL45). Only shrimp treated with inactivated WSSV at PL35 or with IHHNV infection at nauplius 5, zoea 1 and PL22 were alive (4.7% and 4%, respectively) at 10 days post-infection (p.i.). Moreover, at 9 days p.i. there was 100% mortality in all remaining treatments, while there was 94% mortality in shrimp treated with inactivated WSSV at PL35 and 95% mortality in shrimp previously treated with IHHNV at N5, Z1 and PL22. Based on viral genome copy quantification by real-time PCR, surviving shrimp previously challenged with IHHNV at PL22 contained the lowest load of WSSV (0,1 × 103 copies ,g,1 of DNA). In addition, surviving shrimp previously exposed to inactivated WSSV at PL35 also contained few WSSV (0,2 × 103 copies ,g,1 of DNA). Consequently, pre-exposure to either IHHNV or inactivated WSSV resulted in slower WSSV replication and delayed mortality. This evidence suggests a protective role of IHHNV as an interfering virus, while protection obtained by inactivated WSSV might result from non-specific antiviral immune response. [source] Alcohol and Hepatitis C Virus,Interactions in Immune Dysfunctions and Liver DamageALCOHOLISM, Issue 10 2010Gyongyi Szabo Hepatitis C virus infection affects 170 million people worldwide, and the majority of individuals exposed to HCV develop chronic hepatitis leading to progressive liver damage, cirrhosis, and hepatocellular cancer. The natural history of HCV infection is influenced by genetic and environmental factors of which chronic alcohol use is an independent risk factor for cirrhosis in HCV-infected individuals. Both the hepatitis C virus and alcohol damage the liver and result in immune alterations contributing to both decreased viral clearance and liver injury. This review will capture the major components of the interactions between alcohol and HCV infection to provide better understanding for the molecular basis of the dangerous combination of alcohol use and HCV infection. Common targets of HCV and alcohol involve innate immune recognition and dendritic cells, the critical cell type in antigen presentation and antiviral immunity. In addition, both alcohol and HCV affect intracellular processes critical for hepatocyte and immune cell functions including mitochondrial and proteasomal activation. Finally, both chronic alcohol use and hepatitis C virus infection increase the risk of hepatocellular cancer. The common molecular mechanisms underlying the pathological interactions between alcohol and HCV include the modulation of cytokine production, lipopolysaccharide (LPS)-TLR4 signaling, and reactive oxygen species (ROS) production. LPS-induced chronic inflammation is not only a major cause of progressive liver injury and fibrosis, but it can also contribute to modification of the tissue environment and stem cells to promote hepatocellular cancer development. Alteration of these processes by alcohol and HCV produces an environment of impaired antiviral immune response, greater hepatocellular injury, and activation of cell proliferation and dedifferentiation. [source] IL-10 and the resolution of infections,THE JOURNAL OF PATHOLOGY, Issue 2 2008CM Filippi Abstract Chronic viral infections pose serious health concerns, as secondary complications such as immunodeficiencies and cancers are common. Treating such infections with conventional vaccine approaches has proved to be difficult. Studies in animals and humans suggest that vaccine failure is probably due to exhaustion of antiviral T cell responses, which occurs in a number of chronic infections. Attempts to elucidate the causes of impairment of antiviral immunity have pointed to a role for the immunomodulatory cytokine IL-10 in the ability of viruses to establish persistence. Induction of IL-10 production by the host during chronic infection appears to be one of the viral means to alter the class of the antiviral immune response and induce generalized immune suppression. Recent work by us and others suggests that it is possible to resuscitate antiviral immunity by interfering with the IL-10 signalling pathway. Targeting IL-10 thus constitutes a promising alternative to conventional vaccine strategies which have not proved to be successful in treating chronic infections. In addition, sterile cure may be achieved with minimal side-effects by combining agents that alter the IL-10 signalling pathway with other compounds, such as antiviral drugs or interferon, but also agents neutralizing other crucial elements of T cell exhaustion, such as PD-1. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] The IFN regulatory factor 7-dependent type I IFN response is not essential for early resistance against murine cytomegalovirus infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2009Christian Steinberg Abstract IFN regulatory factor 7 (IRF7) has been described as the master regulator of type I IFN responses and has been shown to be critical for innate antiviral immunity in vivo. In addition to type I IFN, NK cell responses are involved in the control of viral replication during acute viral infection. To investigate the role of IRF7 in the context of a viral infection that induces a strong NK cell response, the murine cytomegalovirus (MCMV) infection model was used. WT, IRF7-deficient and IRF3/IRF7-double deficient mice were infected with MCMV. The systemic IFN-, response to MCMV was entirely dependent on IRF7, but independent of IRF3. However, peak IFN-, production during MCMV infection was not affected by the lack of IRF7 or both IRF7 and IRF3. Despite the complete lack of IFN-, production IRF7- and IRF3/IRF7-deficient mice were surprisingly efficient in controlling MCMV replication and were only modestly more susceptible to MCMV infection than WT mice. NK cell cytotoxicity was unimpaired and NK cell IFN-, production was enhanced in IRF7-deficient mice correlating with increased levels of bioactive IL-12. Owing to these compensatory mechanisms IRF7-dependent antiviral immune responses were not essential for resistance against acute MCMV infection in vivo. [source] B7-H1 up-regulation impairs myeloid DC and correlates with disease progression in chronic HIV-1 infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008Xicheng Wang Abstract Impaired myeloid dendritic cells (mDC) fail to elicit host antiviral immune responses, leading to disease progression in HIV-1 infection. However, mechanisms underlying mDC suppression remain elusive. In this study, we found that the T-cell co-stimulatory molecule programmed death-1 ligand-1 (B7-H1) is significantly up-regulated on peripheral mDC in HIV-1-infected typical progressors and AIDS patients, but is maintained at a relatively low level in long-term non-progressors. Successful immune reconstitution after highly active antiretroviral therapy, indicated by full suppression of HIV-1 replication and substantial increases of CD4 T-cell counts, correlated with a decrease in B7-H1 expression. Importantly, we also found that X4 HIV-1 isolates directly induced B7-H1 expression on mDC in vitro, while adding antiviral agents hampered this B7-H1 up-regulation. Blockade of B7-H1 in vitro strongly enhanced mDC-mediated allostimulatory capacity and IL-12 production. In contrast, B7-H1 ligation with soluble programmed death-1 (PD-1) reduced mDC maturation and IL-12 production but increased mDC apoptosis and IL-10 production. Thus, B7-H1 up-regulation may inhibit mDC-mediated immune response, thereby facilitating viral persistence and disease progression in HIV-1-infected patients. This study provides new evidence that B7-H1 inhibitory signaling may reversely mediate functional impairment of mDC in HIV-1 infection, which further supports the notion that B7-H1 blockade represents a novel therapeutic approach to this disease. [source] Hepatitis C virus,infected hepatocytes extrinsically modulate dendritic cell maturation to activate T cells and natural killer cells,HEPATOLOGY, Issue 1 2008Takashi Ebihara Dendritic cell maturation critically modulates antiviral immune responses, and facilitates viral clearance. Hepatitis C virus (HCV) is characterized by its high predisposition to persistent infection. Here, we examined the immune response of human monocyte-derived dendritic cells (MoDCs) to the JFH1 strain of HCV, which can efficiently replicate in cell culture. However, neither HCV RNA replication nor antigen production was detected in MoDCs inoculated with JFH1. None of the indicators of HCV interacting with MoDCs we evaluated were affected, including expression of maturation markers (CD80, 83, 86), cytokines (interleukin-6 and interferon-beta), the mixed lymphocyte reaction, and natural killer (NK) cell cytotoxicity. Strikingly, MoDCs matured by phagocytosing extrinsically-infected vesicles containing HCV-derived double-stranded RNA (dsRNA). When MoDCs were cocultured with HCV-infected apoptotic Huh7.5.1 hepatic cells, there was increased CD86 expression and interleukin-6 and interferon-beta production in MoDCs, which were characterized by the potential to activate NK cells and induce CD4+ T cells into the T helper 1 type. Lipid raft-dependent phagocytosis of HCV-infected apoptotic vesicles containing dsRNA was indispensable to MoDC maturation. Colocalization of dsRNA with Toll-like receptor 3 (TLR3) in phagosomes suggested the importance of TLR3 signaling in the MoDC response against HCV. Conclusion: The JFH1 strain does not directly stimulate MoDCs to activate T cells and NK cells, but phagocytosing HCV-infected apoptotic cells and their interaction with the TLR3 pathway in MoDCs plays a critical role in MoDC maturation and reciprocal activation of T and NK cells. (HEPATOLOGY 2008.) [source] Transgenic mice replicating hepatitis B virus but lacking expression of the major HBsAg,JOURNAL OF MEDICAL VIROLOGY, Issue 4 2008Leonie Halverscheid Abstract Hepatitis B Virus (HBV) transgenic mice replicating the viral genome at high level but lacking expression of the small envelope protein (HBsAg) have been produced using a terminally redundant viral DNA construct (HBV 1.4). The generation of viable infectious progeny was dependent on sex and age of mice. Viral mRNA was abundant in liver and kidneys and at low levels in other organs of the mice. No viral particles or HBV envelope proteins could be detected in sera of mice. Despite expression of non-secreted LHBs and MHBs proteins in the liver, there was no accumulation of viral particles in the endoplasmic reticulum of hepatocytes and no necroinflammatory hepatitis was observed. Therefore, these mice represent an excellent model for studies of the role of HBsAg in viral assembly, antiviral immune responses, the further understanding of HBV immunopathogenesis, and the development of antiviral vaccines. J. Med. Virol. 80:583,590, 2008. © 2008 Wiley-Liss, Inc. [source] Monocyte-derived dendritic cells from HCV-infected patients transduced with an adenovirus expressing NS3 are functional when stimulated with the TLR3 ligand poly(I:C)JOURNAL OF VIRAL HEPATITIS, Issue 11 2008I. Echeverrķa Summary., Dendritic cells (DC) transfected with an adenovirus encoding hepatitis C virus (HCV) NS3 protein (AdNS3) induce potent antiviral immune responses when used to immunize mice. However, in HCV infected patients, controversial results have been reported regarding the functional properties of monocyte-derived DC (MoDC), a cell population commonly used in DC vaccination protocols. Thus, with the aim of future vaccination studies we decided to characterize MoDC from HCV patients transfected with AdNS3 and stimulated with the TLR3 ligand poly(I:C). Phenotypic and functional properties of these cells were compared with those from MoDC obtained from uninfected individuals. PCR analysis showed that HCV RNA was negative in MoDC from patients after the culture period. Also, phenotypic analysis of these cells showed lower expression of CD80, CD86, and CD40, but similar expression of HLA-DR molecules as compared to MoDC from uninfected individuals. Functional assays of MoDC obtained from patients and controls showed a similar ability to activate allogeneic lymphocytes or to produce IL-12 and IL-10, although lower IFN-, levels were produced by cells from HCV patients after poly(I:C) stimulation. Moreover, both groups of MoDC induced similar profiles of IFN-, and IL-5 after stimulation of allogeneic T-cells. Finally, migration assays did not reveal any difference in their ability to respond to CCL21 chemokine. In conclusion, MoDC from HCV patients are functional after transduction with AdNS3 and stimulation with poly(I:C). These findings suggest that these cells may be useful for therapeutic vaccination in chronic HCV infection. [source] Cytotoxic CD4+ T cells in viral hepatitisJOURNAL OF VIRAL HEPATITIS, Issue 8 2006N. Aslan Summary., CD4+ T cells are thought to contribute to antiviral immune responses by secretion of cytokines thereby providing help to CD8+ T and B cells. However, perforin-positive cytotoxic CD4+ T cells have been described in human immunodeficiency virus-positive patients suggesting a role not only of CD8+ but also of CD4+ T cells for killing virus-infected cells. We investigated 76 patients with viral hepatitis [15 hepatitis B virus (HBV), 22 HBV/hepatitis D virus and 17 hepatitis C virus (HCV)] for cytotoxic CD4+ T cells. The frequency of perforin-positive CD4+ T cells in viral hepatitis was highly variable ranging from <1% to more than 25%. Perforin-positive CD4+ T cells displayed the phenotype of terminally differentiated effector cells (CD28,, CD27,). The highest frequencies of CD4+ cytotoxic T lymphocytes (CTLs) were found in patients with delta hepatitis (P = 0.04 vs HBV and HCV patients), and the presence of CD4+ CTLs was associated with elevated aspartate aminotransferase levels (P = 0.01) and decreased platelet counts (P = 0.03). Perforin-positive CD4+ T cells decreased in two individuals during spontaneous clearance of acute hepatitis C. Significant associations were found between the frequency of perforin-expressing CD4+ cells and age (P = 0.04), perforin-positive CD8+ cells (P < 0.001) and perforin-positive CD4,/CD8, lymphoid cells (P = 0.002). Differentiated CD27, effector CD4+ CTLs can be detected in patients with viral hepatitis. In particular in patients with more advanced liver disease, the accumulation of perforin-positive T cells with age could be one correlate for the more severe course of viral hepatitis in elderly individuals. [source] REVIEW ARTICLE: Maternal and Fetal Response to Fetal Persistent Infection with Bovine Viral Diarrhea Virus,AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Thomas R. Hansen Citation Hansen TR, Smirnova NP, Van Campen H, Shoemaker ML, Ptitsyn AA, Bielefeldt-Ohmann H. Maternal and fetal response to fetal persistent infection with bovine viral diarrhea virus. Am J Reprod Immunol 2010 Problem, Infection of naļve pregnant cows with non-cytopathic (ncp) bovine viral diarrhea virus (BVDV) results in transplacental infection of the fetus. Infection of the pregnant cow with ncp BVDV late in gestation (after day 150) results in transient infection (TI), as both the dam and fetus can mount an immune response to the virus. In contrast, if the fetus is infected with ncp BVDV early in gestation (before day 150), the fetal immune system is undeveloped and unable to recognize the virus as foreign. This results in induction of immune tolerance to the infecting BVDV strain and persistent infection (PI). Methods, Infection of naļve pregnant heifers with ncp BVDV2 on day 75 was hypothesized to induce differential gene expression in white blood cells of the dams and their fetuses, adversely affecting development and antiviral immune responses in PI fetuses. Results, Gene expression differed in maternal blood cells in the presence of PI versus uninfected fetuses. PI adversely affected fetal development and antiviral responses, despite protective immune responses in the dam. Conclusion, Fetal PI with BVDV alters maternal immune function, compromises fetal growth and immune responses, and results in expression of maternal blood biomarkers that can be used to identify cows carrying PI fetuses. [source] Dendritic cells in cytomegalovirus infection: viral evasion and host countermeasuresAPMIS, Issue 5-6 2009ALEXANDER RÖLLE Human cytomegalovirus (HCMV) is a ,-herpesvirus that infects the majority of the population during early childhood and thereafter establishes life-long latency. Primary infection as well as spontaneous reactivation usually remains asymptomatic in healthy hosts but can, in the context of systemic immunosuppression, result in substantial morbidity and mortality. HCMV counteracts the host immune response by interfering with the recognition of infected cells. A growing body of literature has also suggested that the virus evades the immune system by paralyzing the initiators of antiviral immune responses , the dendritic cells (DCs). In the current review, we discuss the effects of CMV (HCMV and murine CMV) on various DC subsets and the ensuing innate and adaptive immune responses. The impact of HCMV on DCs has mainly been investigated using monocyte-derived DCs, which are rendered functionally impaired by infection. In mouse models, DCs are targets of viral evasion as well, but the complex cross-talk between DCs and natural killer cells has, however, demonstrated an instrumental role for DCs in the control and clearance of viral infection. Fewer studies address the role of peripheral blood DC subsets, plasmacytoid DCs and CD11c+ myeloid DCs in the response against HCMV. These DCs, rather than being paralyzed by HCMV, are largely resistant to infection, mount a vigorous first-line defense and induce T-cell responses to the virus. This possibly provides a partial explanation for an intriguing conundrum: the highly efficient control of viral infection and reactivation in immunocompetent hosts in spite of multi-layered viral evasion mechanisms. [source] | ||||||||||