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At least 145 records · Page 8Linked to original sources
PubMed2001

Evasion of host immune surveillance by hepatitis C virus: potential roles in viral persistence.

Hepatitis C virus (HCV) is a major human pathogen that causes mild to severe liver disease worldwide. This positive strand RNA virus is remarkably efficient at establishing chronic infections. In order for a noncytopathic virus such as HCV to persist, the virus must escape immune recognition or evade host immune surveillance. Immune escape via the hypervariable region of the E2 envelope protein has been postulated as one mechanism for HCV persistent infection. Such hypervariability within the E2 protein may be under selective pressure from protective B cell or T cell responses and be able to escape immune recognition by rapid mutation of antigenic site. In addition to antigenic variation, HCV may also suppress immune response, leading to dampening of cellular immunity. This is supported by recent studies in our laboratory demonstrating that the HCV core protein can suppress host immune responses to vaccinia virus by downregulating viral specific cytotoxic T lymphocyte (CTL) responses and cytokine production. An understanding of the mechanisms behind HCV persistence will provide a basis for the rational design of vaccines and novel therapeutic agents targeting human HCV infection.

Cytokines↗
PubMed1982

[Acute meningoencephalitis and the problem of viral persistence in complicated rubella].

The results of combined clinico-virological and immunological examinations of 25 children with rubellar meningoencephalitis are presented. The meningoencephalitis was preceded by typical rubella in 24, and by rubellar infection without eruptions in 1 child. In 6 children the rubella virus was isolated from the cerebrospinal fluid in the acute period of the disease (5th to 19th days), and in 2 children it was re-isolated on the acute period of the disease (5th to 19th days), and in 2 children it was re-isolated on the 17th-19th days. A persistence of the immunoglobulins M specific to the rubella virus was revealed both in the acute period of the disease and long time after the disease onset (the observation period was 409 days). The data obtained confirm the etiological role of the rubella virus in the development of rubellar meningoencephalitis, suggesting that the rubella virus may persist in complicated post-natal rubella.

Acute Disease↗
PubMed1998

Adaptation of Theiler's virus to L929 cells: mutations in the putative receptor binding site on the capsid map to neutralization sites and modulate viral persistence.

Persistent strains of Theiler's virus, a murine picornavirus, produce a life-long infection of the central nervous system of the mouse and induce a chronic demyelinating disease. Strain DA1, a molecular clone of such a persistent strain, produces a prominent cytopathic effect in BHK-21 cells but is less efficient at infecting L929 cells. We cloned the cDNA of a derivative of virus DA1, adapted to promote a rapid cytopathic effect in L929 cells. Adaptation of the new variant (named KJ6) to L929 cells correlated with an enhanced viral entry rather than with an increased replication rate of the genome. Mutations responsible for L929 cells adaptation occurred in amino acids exposed at the surface of the capsid, in the CD loop of VP1 (100-102) and in the EF loop of VP2 (162-171-173), suggesting that these residues could be involved in receptor recognition. These two clusters of amino acids are precisely known to be part of neutralization epitopes. They also differentiate persistent from neurovirulent strains of Theiler's virus. Adaptation of the virus to L929 cells was accompanied by attenuation of its virulence for the mouse. Taken together, these data suggest a close relationship between receptor binding, virus neutralization, and virus phenotype.

Adaptation, Physiological↗
PubMed2005

Multigene tracking of quasispecies in viral persistence and clearance of hepatitis C virus.

AIM: To investigate the evaluation of hepatitis C virus (HCV) quasispecies in the envelope region and its relationship with the outcome of acute hepatitis C. METHODS: HCV quasispecies were characterized in specimens collected every 2-6 mo from a cohort of acutely HCV-infected subjects. We evaluated two individuals who spontaneously cleared viremia and three individuals with persistent viremia by cloning 33 1-kb amplicons that spanned E1 and the 5' half of E2, including hypervariable region 1 (HVR1). To assess the quasispecies complexity and to detect variants for sequencing, 33 cloned cDNAs representing each specimen were assessed by a combined method of analysis of a single-stranded conformational polymorphism and heteroduplex analysis. The rates of both synonymous and nonsynonymous substitutions for the E1, HVR1 and E2 regions outside HVR1 were analyzed. RESULTS: Serum samples collected from chronic phase of infection had higher quasispecies complexity than those collected from acute phase of infection in all individuals examined. The genetic diversity (genetic distance) within HVR1 was consistently higher than that in the complete E1 (0.0322+/-0.0068 vs -0.0020+/-0.0014, P<0.05) and E2 regions outside HVR1 (0.0322+/-0.0068 vs 0.0017+/-0.0011, P<0.05) in individuals with persistent viremia, but did not change markedly over time in those with clearance of viremia. For individuals with persistent viremia, the rate of nonsynonymous substitutions within the HVR1 region (2.76X10(-3)+/-1.51X10(-3)) predominated and gradually increased, as compared with that in the E1 and E2 regions outside HVR1 (0.23X10(-3)+/-0.15X10(-3), 0.50X10(-3)+/-0.10X10(-3)). By contrast, the rates of both nonsynonymous and synonymous substitutions for the E1 and E2 regions including HVR1 were consistently lower in individuals with clearance of viremia. CONCLUSION: HCV persistence is associated with a complexity quasispecies and positive selection of HVR1 by the host immune system.

Acute Disease↗
PubMedDate not supplied

Association of avian reovirus M and S genes with viral behavior in vivo. I. Viral persistence.

Persistent infections were initiated in chickens with four different avian reovirus strains of varying virulence. Chickens 1 day old, 1 week old, or 2 weeks old were inoculated with each. Eight weeks later, isolates from all four parent strains were obtained; all isolates but one were from the tendons, and that was from the pancreas. Biochemical characterization of the isolates showed their genomes to be similar to those of the parent strains, although the proteins of the persistent isolates occasionally appeared to migrate differently from those of the original strains. Hybridization studies of the genes of the isolates indicated that at least two genes, S2 and S4, consistently seemed to undergo the greatest degree of mutation in the most virulent strain. These data suggest that the S2 and S4 genes may be associated with initiation and maintenance of persistent infection in vivo, and that changes in these genes may be noted by 56 days postinfection.

Animals↗
PubMed1991

Viral persistence in neurons explained by lack of major histocompatibility class I expression.

Viruses frequently persist in neurons, suggesting that these cells can evade immune surveillance. In a mouse model, 5 x 10(6) cytotoxic T lymphocytes (CTLs), specific for lymphocytic choriomeningitis virus (LCMV), did not lyse infected neurons or cause immunopathologic injury. In contrast, intracerebral injection of less than 10(3) CTL caused disease and death when viral antigens were expressed on leptomeningeal and choroid plexus cells of the nervous system. The neuronal cell line OBL21 expresses little or no major histocompatibility (MHC) class I surface glycoproteins and when infected with LCMV, resisted lysis by virus-specific CTLs. Expression of MHC heavy chain messenger RNA was limited, but beta 2-microglobulin messenger RNA and protein was made normally. OBL21 cells were made sensitive to CTL lysis by transfection with a fusion gene encoding another MHC class I molecule. Hence, neuronal cells probably evade immune surveillance by failing to express MHC class I molecules.

Acute Disease↗
PubMed1999

Quasispecies in viral persistence and pathogenesis of hepatitis C virus.

Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. This RNA virus circulates as a quasispecies and its genetic heterogeneity has been implicated in the lack of protective immunity against HCV and in its persistence following infection. HCV might escape from immune surveillance by developing mutations in proteins that are subject to immune pressure.

Animals↗
PubMed1987

Semliki Forest virus-induced, immune-mediated demyelination: adoptive transfer studies and viral persistence in nude mice.

Adoptive transfer experiments in athymic nude mice demonstrated that the demyelination seen in the central nervous system (CNS) following Semliki Forest virus (SFV) infection was directly dependent upon sensitized T lymphocytes. Antibodies generated during the infection did not seem to be involved in the demyelination, but thymus-dependent antibodies (IgG) were responsible for the reduction of brain virus titres. In the absence of a T cell response and T cell-dependent antibody production, virus persisted in the CNS for several months. Despite persistence of high virus titres for this time, only mice eventually developing a CNS inflammatory response developed lesions of demyelination. In the absence of an inflammatory response no demyelination was apparent even after several months of persistent infection. Administration of anti-SFV hyperimmune serum intracerebrally to both infected and control mice did not produce demyelination but resulted in CNS tissue degeneration with marked pycnosis.

Animals↗
PubMed1996

Virulence as a positive trait in viral persistence.

A population replacement experiment has been devised to test the ability of a challenge virus to replace the resident virus in a persistently infected cell culture. BHK-21 cells persistently infected with foot-and-mouth disease virus of serotype C (clone C-S8c1) were challenged with a large excess of either the parental foot-and-mouth disease virus C-S8c1, genetically marked variants differing in their degree of virulence, or a mutant rescued after prolonged persistence in BHK-21 cells. After challenge, the composition of the resident virus population in the carrier culture was analyzed by reverse transcription-PCR amplification and nucleotide sequencing. The dominance of the initial persisting virus was seen in all cases, except when virulent viruses were used in the challenge. The experiments document that, paradoxically, virulence can be a positive factor in the reestablishment of a virus population in a persistently infected cell culture. A model based on the selection of virus-resistant cell variants during persistence is proposed to interpret these observations. Implications about the persistence of viruses in their host cells and organisms are discussed.

Animals↗
PubMed2001

Inhibition of poliovirus RNA synthesis as a molecular mechanism contributing to viral persistence in the mouse central nervous system.

Many survivors of poliomyelitis, several decades after the acute phase of the disease, develop a set of new muscle symptoms called post-polio syndrome. The persistence of poliovirus (PV) in the central nervous system (CNS) may be involved in the aetiology of this syndrome. By using a mouse model, we have shown that PV persists in the CNS of paralysed mice for over a year after the acute disease. Detection of PV plus- and minus-strand RNAs in the spinal cord of paralysed mice suggested continuous PV RNA replication in the CNS. However, infectious PV particles could not be recovered from homogenates of CNS from paralysed mice beyond 20 days post-paralysis, indicating that PV replication was restricted. In an attempt to identify the molecular mechanism by which PV replication was limited, PV plus- and minus-strand RNA levels were estimated in the CNS of persistently infected mice by a semi-quantitative RT-nested PCR method. Results revealed that RNA replication was inhibited at the level of plus-strand RNA synthesis during persistent infection. Similar results were obtained in neuroblastoma IMR-32 cell cultures persistently infected with PV Restriction of PV RNA synthesis could be involved in persistence by limiting PV replication.

Animals↗
PubMed2000

[Persisting viral infection, serum antibodies and chromosome instability in myasthenia].

There were examined 94 patients, aged from 22 to 68 years, with myasthenia, in whom morphological changes of thymic gland were revealed. In 89% of observations there was established the infectioning by cytomegalovirus, in 10%--hepatitis B, in 9%--hepatitis C. In 5% of patients there were observed coexistence of cytomegaloviral infection and hepatitis. In all the patients the trustworthy increase of the chromosomal aberrations frequency in comparison with spontaneous level of mutation was revealed. High diagnostic validity of chain reaction with polymerase in the viruses persistence determination was noted. The results of investigation of serous immunoglobulins to the virus neutralizing antibodies ratio may be applied for the indications elaboration in the lymphosorption and immunocorrection application in patients with myasthenia more than 4 years in course.

Adult↗
PubMed1999

Theiler's murine encephalomyelitis virus (TMEV): the role of a small out-of-frame protein in viral persistence and demyelination.

Theiler's murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus of the family Picornaviridae and is divided into two subgroups on the basis of different biological activities. GDVII subgroup strains produce acute and fatal polioencephalomyelitis in mice with no virus persistence. In contrast, DA or TO subgroup strains cause an early nonfatal polioencephalomyelitis. TMEV is thought to be an excellent animal model for the human demyelinating disease, multiple sclerosis. Data suggest that macrophages are a major reservoir harboring the virus. A small out-of-frame protein designated L* is synthesized in DA subgroup strains from an alternative, out-of-frame, initiation site. Studies of a DA mutant virus, having an ACG rather than an AUG and therefore does not synthesize L* protein, demonstrate that this protein is important for virus growth in particular cell types and is critical for DA-induced demyelinating disease and virus persistence. In addition, TMEV can be used as a vector for delivering foreign sequences into the central nervous system.

Animals↗
PubMed1991

Viral persistence and disease: cytopathology in the absence of cytolysis.

Realising that viruses could persist and thereby cause chronic disease has been one of the major accomplishments in virology. In this review we will discuss the principles by which viruses can persist and how such persistence can lead to disease. Our focus will be on the ability of certain viruses to interfere subtly with the cell's ability to produce specific differentiated products as hormones, neurotransmitters, cytokines and immunoglobulins, etc., in the absence of their ability to lyse the cell they infect. By this means viruses can replicate in histologically normal appearing cells and tissues. Despite viral replication the infected cell maintains its normal anatomic architecture and yet the virus disorders the differentiated or luxury function of the cell leading to disturbances in homeostasis and disease. Viruses by this means likely underline a wide variety of clinical illnesses, currently of unknown aetiology, that affect the endocrine, immune, nervous and other differentiated systems.

Animals↗
PubMed1996

Vaccination protects beta 2 microglobulin deficient mice from immune mediated mortality but not from persisting viral infection.

Intracranial (i.c.) infection of immunocompetent mice with lymphocytic choriomeningitis virus (LCMV) results in immunopathological lethal meningitis mediated by CD8+ cytotoxic T lymphocytes (CTL). Vaccination of immunocompetent mice elicits a CD8+ CTL response that can protect the mice from lethal meningitis. beta 2 microglobulin-deficient (beta 2m-/-) mice are deficient in CD8+ CTL, exhibit CD4+ CTL, and, after i.c. LCMV infection, undergo a less severe meningitis with decreased mortality and additionally develop a wasting disease. Both wasting disease and mortality in beta 2m-/- mice are mediated by CD4+ T cells. We studied the effects of vaccination and challenge dose on weight loss, mortality and viral clearance after i.c. LCMV infection in beta 2m-/- mice. Unvaccinated beta 2m-/- mice had significant weight loss and mortality at doses of 200 and 10(3) p.f.u. LCMV, while a dose of 10(6) p.f.u. LCMV elicited significant mortality but less weight loss. Vaccination with u.v.-inactivated LCMV in complete Freund's adjuvant or with vaccinia virus expressing the LCMV glycoprotein or nucleoprotein genes protected beta 2m-/- mice from mortality but not weight loss after 200 p.f.u. LCMV challenge. Although protected from mortality, beta 2m-/- mice were unable to clear LCMV from their brains or spleens. Therefore, we show that vaccination can protect against lethal immune-meningitis in the face of persistent infection.

Animals↗
PubMed1977

A new model of persistent viral infection with primary demyelination.

Theiler's encephalomyelitis virus (TMEV) in mice represents one of the few existing animal models of virus-induced demyelination and may provide further information about the human disease, Multiple Sclerosis. An inbred strain of mice (SJL/j) employed in the present ultrastructural study, develops a life-long neurologic illness characterized by profound spasticity after intracerebral inoculation of TMEV. Anesthetized animals were sacrificed sequentially by total body perfusion with gluteraldehyde from 7 days to 9 months after infection. An intense mononuclear inflammatory infiltrate appeared in the leptomeninges and white matter of spinal cord by 15 days and persisted for as long as one year. These infiltrates contained numerous plasma cells, and perivascular demyelination could be found in almost every 1 micron section. Vesiculation and stripping of myelin by mononuclear cell processes were seen as mechanisms of myelin break-down. However, virions were not found in cells in grey or white matter and the integrity of oligodendrocytes was maintained. At one year, active demyelination was still seen in areas containing naked and remyelinated axons. The relevance of these ultrastructural findings to postulated mechanisms of virus-induced demyelination will be discussed.

Animals↗
PubMed1991

Natural history of Coxsackievirus B3-induced myocarditis in ACA/Sn mice: viral persistence demonstrated by quantitative in situ hybridization histochemistry.

Enteroviruses are considered to be the major aetiological agents of myocarditis in humans. Recent in situ hybridization studies on endomyocardial biopsies and autopsy hearts indicate that enterovirus RNA can be detected (pattern of persistent infection) not only in acute myocarditis (pattern of acute infection), but also in chronic dilated cardiomyopathy. Our experimental studies on murine coxsackievirus B3 myocarditis provided evidence that persistent infection may also occur in mice. Quantitative in situ hybridization and immunohistochemistry as well as electron microscopical in situ hybridization experiments were performed on ACA/SnJ mice 3-30 days after infection. The pattern of acute infection (days 3-9 p.i.) is characterized by rapid progression of myocardial lesions, an increasing number of inflammatory cells and a high number of infected myocytes. Hallmarks of the persistent pattern (days 15-30 p.i.) are reduced inflammation, reduced numbers of persistently infected cells and a slow progression of myocardial lesions. Infection is primarily restricted to degenerated, atrophic myocytes and to fibroblasts.

Animals↗
PubMed2005

Evidence for viral persistence in patients who test positive for anti-hepatitis C virus antibodies and have normal alanine aminotransferase levels.

It is unclear whether patients who test positive for anti-hepatitis C virus (HCV) antibodies and have normal alanine aminotransferase (ALT) levels remain infected with the virus. Eleven patients who tested positive for anti-HCV antibodies, had persistently normal ALT levels, and tested negative for HCV RNA by commercial test were studied. Serum and peripheral blood mononuclear cells (PBMCs) were collected 2-3 times at 3-6-month intervals, and PBMCs were cultured with phytohemagglutinin and pokeweed mitogen. HCV RNA was detected in serum samples from 6 (55%) and in PBMCs from 11 (100%) patients. Our results suggest that, in asymptomatic patients who test positive for anti-HCV antibodies, small quantities of HCV RNA commonly persist, even in patients who test negative for HCV RNA in serum by commercial tests.

Adult↗