SEARCH · PubMed Health

Results for “viral persistence”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed1987

Evidence of persistent viral infection in Menière's disease.

Aspects of humoral and cell-mediated immunity that might characterize the continuation of symptoms in 25 patients with chronic Meniere's disease were examined. We found significant elevations of both humoral and cellular immune responses to viral antigens of herpes simplex I, varicella-zoster, rubella, and cytomegalovirus. Serum immunoglobulins were quantitatively abnormal in 24 of 25 patients, without a consistent pattern. These immune responses may be linked to persistent viral infection in chronic Meniere's disease.

Adult↗

PubMed2006

Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease.

Virus infections and autoimmune disease have long been linked. These infections often precede the occurrence of inflammation in the target organ. Several mechanisms often used to explain the association of autoimmunity and virus infection are molecular mimicry, bystander activation (with or without epitope spreading), and viral persistence. These mechanisms have been used separately or in various combinations to account for the immunopathology observed at the site of infection and/or sites of autoimmune disease, such as the brain, heart, and pancreas. These mechanisms are discussed in the context of multiple sclerosis, myocarditis, and diabetes, three immune-medicated diseases often linked with virus infections.

Animals↗

PubMed2000

Prevalence and viral persistence of TT virus in patients on hemodialysis.

The aim of this study was toevaluate the prevalence of TT virus (TTV) in 107 hemodialysis patients and 100 healthy individuals. Sixteen percent of hemodialysis patients and 2% of the control population were TTV positive (P<0.001). Sex, time on dialysis, transfusions, and alanine aminotransferase levels were not related to the presence of TTV DNA. TTV was more frequent in patients 50 to 70 (12/51) years of age and persisted in the serum of six of nine patients 8 months later. TTV was found in peripheral blood mononuclear cells of all patients with chronic infection, and sequence variation was noted in the peripheral blood mononuclear cells of two patients. No relationship between TTV infection and hepatitis was observed. Viral persistence and nonparenteral transmission may be possible in patients on hemodialysis.

Aged↗

PubMed2001

Astrocytes, not microglia, are the main cells responsible for viral persistence in Theiler's murine encephalomyelitis virus infection leading to demyelination.

The BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) persists in the CNS and produces a chronic inflammatory demyelinating disease that is an animal model for human multiple sclerosis (MS). The mechanisms leading to TMEV-induced demyelination are still under study but most likely involve both immune-mediated and virus induced damage to cells in the CNS, both depending on viral persistence. It is therefore important to identify the cells in which continued virus production is permitted. In this study, we looked at virus infection in primary astrocytes, microglia and oligodendrocytes, derived from brains of neonatal susceptible SJL/J mice. As evidenced by Western blots and immunocytochemistry, we were able to detect viral antigens in all these brain-derived cells. In addition, we extended the study to spinal cord tissues from mice suffering TMEV-induced disease. Immunohistochemistry staining with anti-TMEV sera and antibodies to specific cell markers detected viral antigens in all these cells. We then asked the question whether viral antigen present in these cells, particularly in microglia/macrophages, represented true viral replication or not. By using different techniques, including immunoprecipitation experiments and the very sensitive method of negative RNA detection through RNase protection assay, we show that both astrocytes and oligodendroglia permit de novo viral replication and viral protein synthesis but with only minimal cytopathic effects. Of these two cell types, astrocytes carry the brunt of viral replication. In microglia, on the other hand, viral replication is restricted since only minimal amounts of negative RNA copies can be demonstrated, while there are clear signs that some of these cells undergo apoptosis. These findings show that the main cell for viral replication is the astrocyte, rather than the microglia/macrophage. Most of the viral antigen present in macrophages, therefore, is probably the result of phagocytosis, rather than actual viral replication. In view of the demonstrated presence of viral replication in astrocytes and of great amounts of viral antigens in microglia/macrophages, it is possible that both types of cells act as antigen presenting cells during this immunopathological disease.

Animals↗

PubMed1975

Immunopathology of mouse hepatitis virus type 3 infection. III. Clinical and virologic observation of a persistent viral infection.

Three types of viral sensitivity were observed in various mouse strains upon MHV3 infection: resistance, full susceptibility, and semisusceptibility. In the latter type, seen in several inbred strains including C3H, approximately 50% of the adult injected animals resisted to the acute disease. Most of the surviving mice, however, developed a chronic disease with a wasting syndrome and occurrence of paralysis. The chronic period of the disease was characterized by a persistent viral infection, since MHV3 virus was recovered from brain, liver, spleen, and lymph nodes throughout the evolution in most of the animals. In addition, a correlation was observed between the clinical evolution and the titer of virus tested 4 days after infection.

Age Factors↗

PubMed2004

Comprehensive early and lasting loss of memory CD8 T cells and functional memory during acute and persistent viral infections.

Viral infections have been shown to induce lymphopenias that lower memory CD8 T cell frequencies, and they also have been shown to cause a permanent loss of memory cells specific to previously encountered pathogens. In this study, the patterns and significance of virus-induced memory CD8 T cell depletion were examined in mice immune to heterologous (Pichinde, vesicular stomatitis, vaccinia) viruses and subsequently challenged with acute or persistent lymphocytic choriomeningitis virus infections. Memory CD8 T cell loss was comprehensive and occurred in both lymphoid and peripheral tissues of the immune host. The impact of the loss of memory T cells was reflected by in vivo cytotoxicity assays, which showed decreased clearance of epitope-expressing targets. Memory CD8 T cell loss occurred very early (day 2) after infection, and was thereafter sustained, consistent more with an active deletion model than with a competition model. Cross-reactive T cells, in contrast, increased in number, but memory cells were reduced whether or not there was competition from cross-reactive T cells. Memory T cell loss was more profound during persistent infection than after acute infection. Adoptive transfer studies showed that, unlike the resolved acute infection, in which the reduced memory frequencies became stable, memory T cell loss was a continuously ongoing process during persistent infection. This study therefore links an early virus-induced lymphopenia to a subsequent long-term loss of CD8 T cell memory and offers a new mechanism for immune deficiency during persistent viral infections.

Acute Disease↗

PubMed2006

Expression of simian immunodeficiency virus Nef protein in CD4+ T cells leads to a molecular profile of viral persistence and immune evasion.

The Nef protein of human immunodeficiency virus and simian immunodeficiency virus is expressed early in infection and plays an important role in disease progression in vivo. In addition, Nef has been shown to modulate cellular functions. To decipher Nef-mediated changes in gene expression, we utilized DNA microarray analysis to elucidate changes in gene expression in a Jurkat CD4+ T-cell line stably expressing SIV-Nef protein under the control of an inducible promoter. Our results showed that genes associated with antigen presentation including members of the T-cell receptor and major histocompatibility class 1 complex were consistently down-regulated at the transcript level in SIV-Nef-expressing cells. In addition, Nef induced a transcriptional profile of cell-cycle-related genes that support the survival of Nef-expressing cells. Furthermore, Nef enhanced the transcription of genes encoding enzymes and factors that catalyze the biosynthesis of membrane glycolipids and phospholipids. In conclusion, gene expression profiling showed that SIV-Nef induces a transcriptional profile in CD4+ T cells that promotes immune evasion and cell survival, thus facilitating viral persistence.

Antigen Presentation↗

PubMed2000

T lymphocytes activated by persistent viral infection differentially modify the expression of metalloproteinases and their endogenous inhibitors, TIMPs, in human astrocytes: relevance to HTLV-I-induced neurological disease.

Activation of T lymphocytes by human pathogens is a key step in the development of immune-mediated neurologic diseases. Because of their ability to invade the CNS and their increased secretion of proinflammatory cytokines, activated CD4+ T cells are thought to play a crucial role in pathogenesis. In the present study, we examined the expression of inflammatory mediators the cytokine-induced metalloproteinases (MMP-2, -3, and -9) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMP-1, -2, and -3), in human astrocytes in response to activated T cells. We used a model system of CD4+ T lymphocytes activated by persistent viral infection (human T lymphotropic virus, HTLV-I) in transient contact with human astrocytes. Interaction with T cells resulted in increased production of MMP-3 and active MMP-9 in astrocytes despite increased expression of endogenous inhibitors, TIMP-1 and TIMP-3. These data suggest perturbation of the MMP/TIMP balance. These changes in MMP and TIMP expression were mediated, in part, by soluble factors (presumably cytokines) secreted by activated T cells. Integrin-mediated cell adhesion is also involved in the change in MMP level, since blockade of integrin subunits (alpha1, alpha3, alpha5, and beta1) on T cells resulted in less astrocytic MMP-9-induced expression. Interestingly, in CNS tissues from neurological HTLV-I-infected patients, MMP-9 was detected in neural cells within the perivascular space, which is infiltrated by mononuclear cells. Altogether, these data emphasize the importance of the MMP-TIMP axis in the complex interaction between the CNS and invading immune cells in the context of virally mediated T cell activation.

Adult↗

PubMed1997

Vaccination against persistent viral infection exacerbates CD4+ T-cell-mediated immunopathological disease.

Lymphocytic choriomeningitis virus (LCMV) infection of normal mice results in a fatal immunopathologic meningitis mediated by CD8+ cytotoxic T lymphocytes (CTL). We have previously shown that female beta2-microglobulin-deficient (beta2m-/-) mice, which are also deficient in CD8+ T cells, are susceptible to LCMV-induced immune-mediated meningitis, characterized by significant weight loss and mortality. This LCMV disease in beta2m-/- mice is mediated by CD4+ T lymphocytes. Our previous studies have also demonstrated that male beta2m-/- mice are less susceptible than female beta2m-/- mice to LCMV-induced, immune-mediated mortality and weight loss. In this report, we show that vaccination of male beta2m-/- mice enhances immunopathology following intracranial infection with LCMV. We observed increased production of gamma interferon (IFN-gamma), an increase in CD4+ CTL precursor frequency, and an increased frequency of IFN-gamma-producing cells from spleen cells of vaccinated male beta2m-/- mice. Vaccinated male beta2m-/- mice also had significantly increased inflammation in the cerebrospinal fluid (CSF), characterized by a large CD4+ T-cell infiltrate. CSF cells from vaccinated mice showed increased production of IFN-gamma on day 7 postchallenge. Neither vaccinated nor control beta2m-/- mice were able to clear virus, and the two groups had similarly high levels of virus early after infection. These results suggest that the magnitude of the early immune response is more important than the level of virus in the brain in determining the outcome of immunopathology in beta2m-/- mice. We show here that vaccination can increase CD4+ T-cell-dependent immunopathology to a persistent viral infection.

Animals↗

PubMedDate not supplied

[The SSPE model: suggestions for an explication of viral persistence].

The detection of a latent viral flora intrinsic to the central nervous system (CNS) raises the problem to know if some neuropathogenic strains have the property of initiating persistent infections or if the persistence is the result of the immune response particularities at the CNS level. A review is done of the pathogenic explanations of virus persistence in SSPE, followed by the discussion about two pathogenic alternatives issues from the author's studies: the antigenic "drift" hypothesis and the one of the defective interfering particles preferential synthesis.

Antigenic Variation↗

PubMed1999

Selection of CD8+ T cells with highly focused specificity during viral persistence in the central nervous system.

The relationships between T cell populations during primary viral infection and persistence are poorly understood. Mice infected with the neurotropic JHMV strain of mouse hepatitis virus mount potent regional CTL responses that effectively reduce infectious virus; nevertheless, viral RNA persists in the central nervous system (CNS). To evaluate whether persistence influences Ag-specific CD8+ T cells, functional TCR diversity was studied in spleen and CNS-derived CTL populations based on differential recognition of variant peptides for the dominant nucleocapsid epitope. Increased specificity of peripheral CTL from persistently infected mice for the index epitope compared with immunized mice suggested T cell selection during persistence. This was confirmed with CD8+ T cell clones derived from the CNS of either acutely (CTLac) or persistently (CTLper) infected mice. Whereas CTLac clones recognized a broad diversity of amino acid substitutions, CTLper clones exhibited exquisite specificity for the wild-type sequence. Highly focused specificity was CD8 independent but correlated with longer complementarity-determining regions 3 characteristic of CTLper clonotypes despite limited TCR alpha/beta-chain heterogeneity. Direct ex vivo analysis of CNS-derived mononuclear cells by IFN-gamma enzyme-linked immunospot assay confirmed the selection of T cells with narrow Ag specificity during persistence at the population level. These data suggest that broadly reactive CTL during primary infection are capable of controlling potentially emerging mutations. By contrast, the predominance of CD8+ T cells with dramatically focused specificity during persistence at the site of infection and in the periphery supports selective pressure driven by persisting Ag.

Amino Acid Sequence↗

PubMed2000

Influence of the Theiler's virus L* protein on macrophage infection, viral persistence, and neurovirulence.

The genome of picornaviruses contains a large open reading frame (ORF) translated as a precursor polypeptide that is processed to yield all the proteins necessary for the viral life cycle. In persistent but not in neurovirulent strains of Theiler's virus, an overlapping ORF encodes an additional 18-kDa protein called L*. We confirmed previous work showing that the L* ORF of persistent strains facilitates the infection of macrophage cell lines, and we present evidence that this effect is due to the L* protein itself rather than to competition for the translation of the two overlapping ORFs. The introduction of an AUG codon to restore the L* ORF of the neurovirulent GDVII strain also enhanced the infection of macrophages, in spite of the divergent evolution of this protein. The presence or the absence of the L* AUG initiation codon had only a weak influence on the neurovirulence of the GDVII strain and on the persistence of the DA1 strain. The results obtained with DA1 in vivo contrast with the results reported previously for DAFL3, another molecular clone of the same virus strain, where the AUG-to-ACG mutation of the L* initiation codon totally blocked viral persistence (G. D. Ghadge, L. Ma, S. Sato, J. Kim, and R. P. Roos, J. Virol. 72:8605-8612, 1998). Thus, a factor that is critical for the persistence of a given clone of Theiler's virus is dispensable for the persistence of a closely related clone, indicating that different adjustments in the expression of persistence determinants occur in related viral strains.

Animals↗

PubMed1992

Differential expression of Hz-1 baculovirus genes during productive and persistent viral infections.

Hz-1 viral RNA transcription was studied during productive and persistent infections. The RNAs were localized to 10- to 30-kb regions within the viral genome, and the timing of their expression was determined. During productive infections, we detected 101 virus-specific transcripts that could be grouped into three categories by time of appearance. At 2 h postinoculation (p.i.), a total of 34 virus-specific transcripts were detected. An additional 51 and 16 virus-specific transcripts appeared between 4 and 6 h p.i. and at 8 h p.i., respectively. After 8 h, no new transcripts were found. Under conditions of persistent infection, we detected only one viral persistency-associated transcript (PAT1). The region of the viral DNA which encodes PAT1 was cloned. During productive infections, three transcripts were derived from this region. Each had the same polarity as PAT1. One of them was of the same size as PAT1 and had similar, if not identical, 3' and 5' ends. This report provides detailed and very useful information concerning sequentially expressed transcripts of the Hz-1 baculovirus.

Animals↗

PubMedDate not supplied

Acute and persistent viral infections of differentiated nerve cells.

Within the nervous system the highly specialized structure and function of nerve cells renders the pathogenesis of viral infections amazingly complex. In vivo and in vitro studies reveal that viruses may display tropism for distinct types of cells such as neurons, myelin-forming cells, or astrocytes. In neurons, RNA viruses mature in the cell body and in dendrites close to synapses, from which they can spread to synaptic endings. Undefined host factors and stage of differentiation may favor defective viral assembly, which, in turn, results in persistent infections of neurons. In myelin-forming cells, lytic infection results is persistent infections of neurons. In myelin-forming cells, lytic infection results in degeneration of myelin and, consequently, in altered conduction in those axons that are ensheathed by a myelin-forming cell. In addition, breakdown of myelin may induce an autoimmune response, which then leads to further demyelination. Autoimmune demyelination may also occur when glial cells other than myelin-forming cells are infected. Astrocytes are prone to persistent infection or viral transformation.

Animals↗

PubMed1984

Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence.

We studied the mechanism of lymphocytic choriomeningitis virus (LCMV) persistence and the suppression of cytotoxic T lymphocyte (CTL) responses in BALB/c WEHI mice infected at birth with LCMV Armstrong strain. Using adoptive transfer experiments we found that spleen cells from persistently infected (carrier) mice actively suppressed the expected LCMV-specific CTL response of spleen cells from normal adult mice. The suppression was specific for the CTL response and LCMV -specific antibody responses were not affected. Associated with the specific CTL suppression was the establishment of persistent LCMV infection. The transfer of spleen or lymph node cells containing LCMV -specific CTL resulted in virus clearance and prevented establishment of the carrier state. The suppression of LCMV -specific CTL responses by carrier spleen cells is not mediated by a suppressor cell, but is due to the presence of genetic variants of LCMV in spleens of carrier mice. Such virus variants selectively suppress LCMV-specific CTL responses and cause persistent infections in immunocompetent mice. In striking contrast, wild-type LCMV Armstrong, from which these variants were generated, induces a potent CTL response in immunocompetent mice and the LCMV infection is rapidly cleared. Our results show that LCMV variants that emerge during infection in vivo play a crucial role in the suppression of virus-specific CTL responses and in the maintenance of virus persistence.

Acute Disease↗

PubMed1990

Viral persistence and immune dysfunction.

Viruses can persist for years without provoking an effective host immune response or otherwise causing the cell destruction characteristic of an acute viral infection. Clinically relevant principles, generalizable to many persistent viruses, are exemplified by measles and lymphocyte choriomeningitis viruses. The LCMV model indicates that viral persistence and the anergic state are reversible.

Animals↗

PubMed2006

Persistent infection of RAW264.7 macrophages with the DA strain of Theiler's murine encephalomyelitis virus: An in vitro model to study viral persistence.

Theiler's murine encephalomyelitis virus (TMEV) is a member of the Picornaviridae family and causes a virus strain dependent pathology in the central nervous system of mice. The GDVII strain induces an acute and mostly fatal encephalomyelitis. In the few mice that survive, the virus is cleared by the immune system. In contrast, infection with the DA strain leads to a persistent infection, marked by inflammation and demyelination that resembles multiple sclerosis. In the DA-induced disease, macrophages play a crucial role because they contribute to demyelination by the secretion of toxic mediators. Moreover, they represent the main viral reservoir, hereby also underlining their essential role in TMEV persistence. The mechanism of this persistence is not yet understood and tools to investigate it directly, without the complexity imposed by experimental animals, are largely missing. By studying TMEV infection of RAW264.7 macrophages, we found that the DA strain establishes a persistent infection in these cells, in contrast to the neurovirulent GDVII strain. Whereas the GDVII strain was cleared within 4 to 5 days post infection, DA virions were still present after 1 year of cell cultivation. This persistently DA-infected macrophage cell line, which we have called DRAW, provides a model to investigate the interactions between the cellular and viral factors influencing persistence and to screen for anti-TMEV agents.

Animals↗

PubMed1994

How could infectious agents hide in synovial cells? Possible mechanisms of persistent viral infection in a model for the etiopathogenesis of chronic arthritis.

It has been hypothesized that a persistent intra-articular viral infection might play an important part in the pathogenesis of chronic arthritis. However, it remains unclear how such an infection could survive in synovial cells that express large amounts of HLA-DR and intercellular adhesion molecule-1 (ICAM-1) by which they communicate with immunocompetent cells. In an in vitro model of persistent mumps virus infection of synovial cells, results suggested that, in contrast to mock-infected cells, cells containing viral antigen did not express HLA-DR in response to interferon-gamma and that they did not up-regulate ICAM-1 expression under these conditions. Previously it has been shown that infected synovial cells do not express viral surface antigens. By these mechanisms, infected cells, interspersed among a large majority of uninfected cells, might evade recognition and eradication by the immune system. Lack of neoantigen expression on infected cells might be an important viral strategy to maintain a persistent infection and to initiate and perpetuate joint inflammation.

Antigens, Viral↗