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Virus Persistence (virus + persistence)
Selected AbstractsNatural killer cells in viral hepatitis: facts and controversiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2010Mario U. Mondelli Eur J Clin Invest 2010; 40 (9): 851,863 Abstract Background, Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major human hepatotropic pathogens responsible for a large number of chronic infections worldwide. Their persistence is thought to result from inefficiencies of innate and adaptive immune responses; however, very little information is available on the former. Natural killer (NK) cells are a major component of innate immunity and their activity is tightly regulated by several inhibitory and activating receptors. Design, In this review, we examine controversial findings regarding the role of NK cells in the pathogenesis of acute and chronic liver disease caused by HCV and HBV. Results, Recent studies built up on technical advances to identify NK receptors and their functional correlates in this setting. While NK cells seem to behave correctly during acute hepatitis, it would appear that the NK cytotoxic potential is generally conserved in chronic hepatitis, if not increased in the case of HCV. In contrast, their ability to secrete antiviral cytokines such as interferon ex vivo or after cytokine stimulation is severely impaired. Conclusions, Current evidence suggests the existence of an NK cell functional dichotomy, which may contribute to virus persistence, while maintaining low-level chronic liver inflammation. The study of liver-infiltrating NK cells is still at the very beginning, but it is likely that it will shed more light on the role of this simple and at the same time complex innate immune cell in liver disease. [source] MULTIPLE HIV-1 INFECTION OF CELLS AND THE EVOLUTIONARY DYNAMICS OF CYTOTOXIC T LYMPHOCYTE ESCAPE MUTANTSEVOLUTION, Issue 9 2009Dominik Wodarz Cytotoxic T lymphocytes (CTL) are an important branch of the immune system, killing virus-infected cells. Many viruses can mutate so that infected cells are not killed by CTL anymore. This escape can contribute to virus persistence and disease. A prominent example is HIV-1. The evolutionary dynamics of CTL escape mutants in vivo have been studied experimentally and mathematically, assuming that a cell can only be infected with one HIV particle at a time. However, according to data, multiple virus particles frequently infect the same cell, a process called coinfection. Here, we study the evolutionary dynamics of CTL escape mutants in the context of coinfection. A mathematical model suggests that an intermediate strength of the CTL response against the wild-type is most detrimental for an escape mutant, minimizing overall virus load and even leading to its extinction. A weaker or, paradoxically, stronger CTL response against the wild-type both lead to the persistence of the escape mutant and higher virus load. It is hypothesized that an intermediate strength of the CTL response, and thus the suboptimal virus suppression observed in HIV-1 infection, might be adaptive to minimize the impact of existing CTL escape mutants on overall virus load. [source] Genetic and catalytic efficiency structure of an HCV protease quasispecies,HEPATOLOGY, Issue 4 2007Sandra Franco The HCV nonstructural protein (NS)3/4A serine protease is not only involved in viral polyprotein processing but also efficiently blocks the retinoic-acid,inducible gen I and Toll-like receptor 3 signaling pathways and contributes to virus persistence by enabling HCV to escape the interferon antiviral response. Therefore, the NS3/4A protease has emerged as an ideal target for the control of the disease and the development of new anti-HCV agents. Here, we analyzed, at a high resolution (approximately 100 individual clones), the HCV NS3 protease gene quasispecies from three infected individuals. Nucleotide heterogeneity of 49%, 84%, and 91% were identified, respectively, which created a dense net that linked different parts of the viral population. Minority variants having mutations involved in the acquisition of resistance to current NS3/4A protease inhibitors (PIs) were also found. A vast diversity of different catalytic efficiencies could be distinguished. Importantly, 67% of the analyzed enzymes displayed a detectable protease activity. Moreover, 35% of the minority individual variants showed similar or better catalytic efficiency than the master (most abundant) enzyme. Nevertheless, and in contrast to minority variants, master enzymes always displayed a high catalytic efficiency when different viral polyprotein cleavage sites were tested. Finally, genetic and catalytic efficiency differences were observed when the 3 quasispecies were compared, suggesting that different selective forces were acting in different infected individuals. Conclusion: The rugged HCV protease quasispecies landscape should be able to react to environmental changes that may threaten its survival. (HEPATOLOGY 2007;45:899,910.) [source] Modelling hantavirus in fluctuating populations of bank voles: the role of indirect transmission on virus persistenceJOURNAL OF ANIMAL ECOLOGY, Issue 1 2003Frank Sauvage Summary 1Using field data published in the literature, we investigated pathogen dynamics and conditions of persistence in a mathematical model of the bank vole (Clethrionomys glareolus),Puumala hantavirus system. The host population is assumed to have a 3-year periodic cycle. The duration of very low host density is critical for virus transmission and survival. 2Field epidemiological data strongly suggested a transmission of the hantavirus by the contaminated environment. We thus studied whether this ,indirect' transmission affected the virus persistence in the host population. 3The model assumptions were derived from the following conditions found in the literature: (1) there is no additional mortality nor fecundity loss due to the virus in infected hosts, thus the cyclic demographical pattern is not due to the virus; (2) no remission has been observed, thus we did not consider the existence of recovered individuals; (3) adult females are territorial and juveniles disperse to find a new territory and reach sexual maturity. A fragmented landscape was assumed to occur: individuals can live in favourable or unfavourable patches. 4The model was a compartmental model; the population was structured into susceptible or infectious individuals. We considered two age classes, juveniles and adults, and two sites (populations) connected by juvenile dispersal. 5Model dynamics accurately predicted the cyclic trend in disease prevalence as observed in epidemiological studies. They also showed that indirect transmission significantly increased the probability for the virus to persist during the low-density period of the host population. More precisely, even a low survival rate of the virus outside the host was sufficient to decrease extinction risk of the infection by stochastic events. 6Elasticity analysis showed a high robustness of the model to changes in the parameters of indirect transmission but a high sensitivity to changes in adult density. [source] Absence of detectable measles virus genome sequence in blood of autistic children who have had their MMR vaccination during the routine childhood immunization schedule of UKJOURNAL OF MEDICAL VIROLOGY, Issue 5 2006M.A. Afzal Abstract Leukocyte preparations from children with documented evidence of MMR vaccination and confirmed diagnosis of autism were examined by several assays designed to target multiple regions of the measles virus genome sequence. No sample was found positive by any method. The assays applied were highly sensitive, specific and robust in nature, and were based on the amplification of measles virus RNA transcripts by real-time quantitative RT-PCR (QRT-PCR) as well as by conventional RT-PCR-nested PCR. The assays applied were potentially able to detect measles virus RNA down to single figure copy numbers per reaction. The amount of total nucleic acid extract of leukocytes subjected to various measles virus-specific investigations was several fold higher than minimally required of a sample where measles virus persistence is well documented. This study failed to substantiate reports of the persistence of measles virus in autistic children with development regression. J. Med. Virol. 78:623,630, 2006. © 2006 Wiley-Liss, Inc. [source] Suppression of proinflammatory cytokines and induction of IL-10 in human monocytes after coxsackievirus B3 infectionJOURNAL OF MEDICAL VIROLOGY, Issue 4 2001P. Hofmann Abstract Coxsackievirus B3 (CVB3) causes acute and chronic myocarditis, which is accompanied by an intense mononuclear leukocyte infiltration. Because myocardial tissue damage may either result from viral infections or from a dysregulated immune response, the susceptibility of human monocytes and macrophages to CVB3 was examined in this study with regard to virus replication, virus persistence, and release of cytokines. Monocytes were infected by CVB3 as shown by the intracellular appearance of plus- and minus-strand viral RNA, which was also capable of persisting for more than 10 days. Fresh monocytes were not permissive for full virus replication whereas monocyte-derived macrophages yielded a low amount of new viruses, which led to cell death. Although CVB3 infection induced the mRNA for the proinflammatory cytokines tumor necrosis factor-alpha (TNF-,), interleukin (IL)-1, and IL-6, only little cytokine production occurred. When infected monocytes were stimulated in addition by lipopolysaccharides (LPS), cytokine production was partially suppressed. In striking contrast, IL-10 expression was strongly and persistently induced by CVB3 on the mRNA and the protein level. These data show a dysregulated cytokine response in CVB3-exposed human monocytes and macrophages, which is characterized by a suppression of proinflammatory cytokines and a dominance of IL-10. This viral strategy may aid CVB3, causing chronic myocardiopathy. J. Med. Virol. 64:487,498, 2001. © 2001 Wiley-Liss, Inc. [source] Role of tumor cell immune escape mechanisms in cytomegalovirus-mediated oncomodulationMEDICINAL RESEARCH REVIEWS, Issue 2 2005Jindrich Cinatl Jr. Abstract It has been known for a long time that cytomegalovirus (CMV) has evolved mechanisms that allow the escape from the host immune surveillance. In the past, many efforts have been done to elucidate the molecular mechanisms underlying this virus-mediated immune escape and thus virus persistence. However, it is unknown, whether CMV may also impair immune responses directed against tumor cells. This might have severe consequences on tumor progression and may explain the growing evidence for CMV-mediated oncomodulation. This review summarizes recent work on CMV-mediated immune escape mechanisms of tumor cells and oncomodulation and proposes novel aspects that may be important for understanding the CMV-associated tumor progression. © 2004 Wiley Periodicals, Inc. [source] Synergism between plant viruses: a mathematical analysis of the epidemiological implicationsPLANT PATHOLOGY, Issue 6 2001X.-S. Zhang Many virus diseases of plants are caused by a synergistic interaction between viruses within the host plant. Such synergism can induce symptoms more severe than would be caused by additive effects. In a synergistic interaction, the virus titre of both, one, or neither virus may be enhanced and, as a consequence, the rate of disease spread may be affected. An epidemiological model was developed in which transmission and loss rates were attributed to the different virus infection possibilities. Sharing the same host population implies competition, and this imposes an increased constraint on the survival of both viruses. It was shown that, in order to ensure virus survival in a mixed infection, the basic reproductive number should exceed a critical value which is larger than unity (R0 > Rc > 1). Here R0 is used in the same sense as in the absence of superinfection. Increased virulence (equivalent to disease severity) in dually infected plants decreases the opportunities for both viruses to coexist, while increased virus transmission from dually infected plants increases such opportunities. The net effect of increased virulence and increased virus transmission on virus persistence was neutral if synergism caused the same proportional effect on both. Total host abundance was, however, reduced. The opportunity for virus persistence was increased if the enhancement of transmission exceeded that of virulence. Indeed, by this mechanism a virus which was nonviable alone could invade and persist in a chronic epidemic of another virus. Where the effect on virulence is greater than that on transmission, the viruses are likely to exclude each other, especially when the transmission rates of both viruses have intermediate values. In such cases, the final outcome is determined by both the parameter values and the initial state. [source] JC virus persistence following progressive multifocal leukoencephalopathy in multiple sclerosis patients treated with natalizumab,ANNALS OF NEUROLOGY, Issue 3 2010Caroline F. Ryschkewitsch MT JC virus (JCV) DNA in the cerebrospinal fluid (CSF) provides the laboratory confirmatory diagnosis of progressive multifocal leukoencephalopathy (PML) in patients whose clinical symptoms and magnetic resonance imaging findings are consistent with PML. The Laboratory of Molecular Medicine and Neuroscience (LMMN), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), made the confirmatory laboratory diagnosis in 35 multiple sclerosis (MS) patients treated with natalizumab. Thirteen patients had 3 or more CSF samples taken from weeks to months following PML diagnosis. Seven of the 13 patients demonstrated persistence of JCV DNA in the CSF even though all patients experienced immune reconstitution inflammatory syndrome (IRIS), 11 patients had plasma exchange, and 2 had immunoabsorption. Specific anti-JCV antibody was measured in plasma/sera samples from 25 of the 35 patients. Most of the samples showed moderate to high or rising antibody levels from the time of PML diagnosis. However, plasma from 1 patient at or near the time of PML diagnosis had a titer considered seronegative and 2 other plasma samples from patients had titers considered at baseline for seropositivity. In several PML cases, viral persistence and neurological deficits have continued for several years, indicating that once initiated, JCV infection may not entirely clear, even with IRIS. Ann Neurol 2010;68:384,391 [source] Epstein-Barr virus persistence and reactivation in myasthenia gravis thymusANNALS OF NEUROLOGY, Issue 6 2010Paola Cavalcante PhD Objective Increasing evidence supports a link between Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic human herpesvirus, and common B-cell,related autoimmune diseases. We sought evidence of EBV infection in thymuses from patients with myasthenia gravis (MG), an autoimmune disease characterized by intrathymic B-cell activation. Methods Seventeen MG thymuses (6 follicular hyperplastic, 6 diffuse hyperplastic, 5 involuted) and 6 control thymuses were analyzed using in situ hybridization for EBV-encoded small RNAs (EBERs), immunohistochemistry for EBV latent and lytic proteins, and polymerase chain reaction for EBV DNA and mRNA. Results All 17 MG thymuses showed evidence of active EBV infection, whereas none of the control thymuses were infected. Cells expressing EBERs (12 of 17) and EBV latency proteins (EBNA2, LMP1, and LMP2A) (16 of 17) were detected in medullary infiltrates and in germinal centers. Cells expressing early (BFRF1, BMRF1) and late (p160, gp350/220) lytic phase EBV proteins were present in 16 MG thymuses. Latency (EBNA1, LMP2A) or lytic (BZLF1) transcripts (often both) were present in all MG thymuses, and EBV DNA (LMP1 gene) was detected in 13 MG thymuses. We also found CD8+ T cells, CD56 + CD3-natural killer cells, and BDCA-2+ plasmacytoid dendritic cells in immune infiltrates of MG thymuses, but not germinal centers, suggesting an attempt of the immune system to counteract EBV infection. Interpretation Dysregulated EBV infection in the pathological thymus appears common in MG and may contribute to the immunological alterations initiating and/or perpetuating the disease. ANN NEUROL 2010;67:726,738 [source] Pathogenesis of Theiler's murine encephalomyelitis virus-induced diseaseCLINICAL AND EXPERIMENTAL NEUROIMMUNOLOGY, Issue 2 2010Raymond P. Roos Abstract Theiler's murine encephalomyelitis virus (TMEV) is a member of the Cardiovirus genus of the Picornaviridae family. Interest in TMEV is at least partly related to the fact that the Daniels (DA) strain and other members of Theiler's original (TO) subgroup induce an inflammatory demyelinating disease in which the virus persists for the life of the mouse. This disease resembles multiple sclerosis because of the similar pathology and because the immune system seems to play an important role in both. The present review describes features of TMEV and the importance of both virus persistence as well as the immune system in the pathogenesis of DA virus-induced demyelinating disease. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759-1961.2010.00008.x, 2010) [source] | |||||||||||||