Viral Load and a Locus on Chromosome 11 Affect the Late Clinical Disease Caused by Theiler’s Virus

Aubagnac, Stéphanie; Brahic, Michel; Bureau, Jean‐François

doi:10.1128/jvi.73.10.7965-7971.1999

Cited by 26 publications

(7 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IFN-γR-/-mice display a rapid decline in motor function, becoming paralyzed and moribund by 7 wk after infection with TMEV (19,20). To deplete D b :VP2 121-130 epitope-specific CD8+ T cells from the population of brain-infiltrating CTL for the full duration of TMEV infection of IFN-γR-/-mice, VP2 121-130 peptide was administered intravenously weekly.…”

Section: Inhibition Of the Cd8+ T Cell Response Toward The Immunodomimentioning

confidence: 99%

Preservation of motor function by inhibition of CD8+ virus peptide‐specific T cells in Theiler's virus infection

Johnson¹,

Upshaw²,

Pavelko³

et al. 2001

FASEB j.

View full text Add to dashboard Cite

Central nervous system-infiltrating CD8+ T cells are potential mediators of neuropathology in models of multiple sclerosis induced by Theiler's murine encephalomyelitis virus (TMEV) infection. C57BL/6 mice mount a vigorous cytotoxic T lymphocyte (CTL) response against the immunodominant virus peptide VP2121-130 and clear TMEV infection. Interferon-g (IFN-g)R-/- mice also mount a strong CTL response against the VP2121-130 epitope, but because of genetic deficiencies in critical IFN-g signaling pathways, they do not clear TMEV infection and develop prominent neurological deficits within 6 wk. This pronounced disease process, coupled with a defined CTL response, provides an ideal model for evaluating the importance of antiviral CTL activity in the development of severe demyelination and loss of motor neuron function. By administering the VP2121-130 peptide before and during TMEV infection, 99% of the VP2121-130-specific CD8+ T cell response was inhibited. No decrease in virus infection was observed. Peptide treatment did result in significantly less motor dysfunction, even when no differences in levels of demyelination were observed. Although most investigators focus on the role of CD4+ T cells in demyelinating disease, these studies are the first to demonstrate a clear contribution of antiviral CD8+ T cells in neurological injury in a chronic-progressive model of multiple sclerosis.

show abstract

Section: Inhibition Of the Cd8+ T Cell Response Toward The Immunodomimentioning

confidence: 99%

Preservation of motor function by inhibition of CD8+ virus peptide‐specific T cells in Theiler's virus infection

Johnson¹,

Upshaw²,

Pavelko³

et al. 2001

FASEB j.

View full text Add to dashboard Cite

show abstract

“…In contrast, susceptible strains of mice fail to generate an effective immune response during early infection, resulting in viral persistence and subsequent immune-mediated demyelination during the chronic phase (Lipton and Melvold, 1984;Rodriguez et al, 1983;Olezak et al, 2004). Although susceptibility to TMEV-induced demyelination is genetically regulated (Brahic and Bureau, 1998;Brahic et al, 2005), other factors that influence the initial immune response play an important role in determining viral load and the degree of viral persistence, thereby altering disease progression and severity (Aubagnac et al, 1999;Brahic et al, 2005;Rodriguez et al, 1996). For example, depletion of CD8 cells or exposure to chronic social stress prior to infection exacerbates disease (Borrow et al, 1992;Johnson et al, 2004;Johnson et al, 2006).…”

mentioning

confidence: 99%

Interleukin-6 as a mechanism for the adverse effects of social stress on acute Theiler’s virus infection

Meagher

Johnson

Young

et al. 2007

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

Prior exposure to social disruption stress (SDR) exacerbates both the acute and chronic phase of Theiler's murine encephalomyelitis virus infection (TMEV; [Johnson, R.R., Storts, R., Welsh, T.H., Jr., Welsh, C.J., Meagher, M.W., 2004. Social stress alters the severity of acute Theiler's virus infection. J. Neuroimmunol. 148, 74--85; Johnson, R.R., Prentice, T.W., Bridegam, P., Young, C.R., Steelman, A.J., Welsh, T.H., Welsh, C.J.R., Meagher, M.W., 2006. Social stress alters the severity and onset of the chronic phase of Theiler's virus infection. J. Neuroimmunol. 175, 39--51]). However, the neuroimmune mechanism(s) mediating this effect have not been determined. The present study examined whether stress-induced increases in the proinflammatory cytokine interleukin-6 (IL-6) contributes to the adverse effects of SDR on acute TMEV infection. Experiment 1 demonstrated that SDR increases central and peripheral levels of IL-6 and that this effect is reversed by intracerebral ventricular infusion of neutralizing antibody to IL-6 prior to each of six SDR sessions. Although SDR reduced the sensitivity of spleen cells to the anti-inflammatory effects of corticosterone, the neutralizing antibody to IL-6 did not alter this effect. To investigate whether stress-induced increases in IL-6 contribute to the exacerbation of acute TMEV infection, Experiment 2 examined whether intracerebral administration of neutralizing antibody to IL-6 during SDR would prevent the subsequent exacerbation of acute TMEV infection. Experiment 3 then replaced the social stress with intracerebral infusion of IL-6 to assess sufficiency. As expected, prior exposure to SDR subsequently increased infection-related sickness behaviors, motor impairment, CNS viral titers, and CNS inflammation. These deleterious effects of SDR were either prevented or significantly attenuated by intracerebral infusion of neutralizing antibody to IL-6 during the stress exposure period. However, infusion of IL-6 alone did not mimic the adverse effects of SDR. We conclude that IL-6 is necessary but not sufficient to exacerbate acute TMEV infection.

show abstract

“…Previous studies have identified genetic factors linked to TMEV resistance or susceptibility, with these responses defined in relation to TMEV-induced demyelinating disease or viral persistence [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. In fact, TMEV infection outcome has been studied in one of the eight CC founder strains: the TMEV-resistant strain C57BL/6J.…”

Section: Introductionmentioning

confidence: 99%

Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions

Brinkmeyer-Langford

Amstalden

Konganti

et al. 2021

IJMS

View full text Add to dashboard Cite

Virus-induced neurological sequelae resulting from infection by Theiler’s murine encephalomyelitis virus (TMEV) are used for studying human conditions ranging from epileptic seizures to demyelinating disease. Mouse strains are typically considered susceptible or resistant to TMEV infection based on viral persistence and extreme phenotypes, such as demyelination. We have identified a broader spectrum of phenotypic outcomes by infecting strains of the genetically diverse Collaborative Cross (CC) mouse resource. We evaluated the chronic-infection gene expression profiles of hippocampi and thoracic spinal cords for 19 CC strains in relation to phenotypic severity and TMEV persistence. Strains were clustered based on similar phenotypic profiles and TMEV levels at 90 days post-infection, and we categorized distinct TMEV response profiles. The three most common profiles included “resistant” and “susceptible,” as before, as well as a “resilient” TMEV response group which experienced both TMEV persistence and mild neurological phenotypes even at 90 days post-infection. Each profile had a distinct gene expression signature, allowing the identification of pathways and networks specific to each TMEV response group. CC founder haplotypes for genes involved in these pathways/networks revealed candidate response-specific alleles. These alleles demonstrated pleiotropy and epigenetic (miRNA) regulation in long-term TMEV infection, with particular relevance for resilient mouse strains.

show abstract

Viral Load and a Locus on Chromosome 11 Affect the Late Clinical Disease Caused by Theiler’s Virus

Cited by 26 publications

References 38 publications

Preservation of motor function by inhibition of CD8+ virus peptide‐specific T cells in Theiler's virus infection

Preservation of motor function by inhibition of CD8+ virus peptide‐specific T cells in Theiler's virus infection

Interleukin-6 as a mechanism for the adverse effects of social stress on acute Theiler’s virus infection

Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions

Contact Info

Product

Resources

About