Theiler's virus and Mengo virus induce cross-reactive cytotoxic T lymphocytes restricted to the same immunodominant VP2 epitope in C57BL/6 mice

Dethlefs, Sven; Escriou, Nicolas; Brahic, Michel; Werf, Sylvie van der; Larsson-Sciard, Eva-Lotta

doi:10.1128/jvi.71.7.5361-5365.1997

Cited by 62 publications

(34 citation statements)

References 30 publications

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“…H-2K s but not H-2D s restriction of virus-specific cytotoxicity in the CNS of TMEV DA-infected mice has also been reported by other groups (240,241). The discrepancy between these results and those reported by other groups describing the low level and late appearance of CTL in SJL mice could be attributed to the fibroblast cell line (KSSV [H-2 s ]) routinely used as target cells in these CTL experiments (97,241,242,244). This cell line expresses low level of H-2K s .…”

Section: Cytotoxic T Lymphocytescontrasting

confidence: 66%

“…At about 3 months p.i., in addition to viral epitopes, other epitopes of PLP were presented by APC from the CNS of TMEV-infected mice, including PLP (56-70), PLP (104)(105)(106)(107)(108)(109)(110)(111)(112)(113)(114)(115)(116)(117), and PLP (178)(179)(180)(181)(182)(183)(184)(185)(186)(187)(188)(189)(190)(191) (199). DTH responses to MOG (92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106) and to MBP(84-104) have also been detected late in the course of demyelinating disease (199). Studies by Dal Canto et al revealed that epitope spreading has functional activity, because lymphocytes from mice chronically infected with TMEV produced demyelination of organotypic cultures after stimulation with the major en...…”

Section: Tmev-induced Disease In Susceptible Micementioning

confidence: 99%

“…These criteria have been applied to generate a minimal molecular mimicry peptide. This structural motif has been used to search a sequence database for viral and bacterial mimicry peptides of MBP (85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99). The search yielded 129 viral and bacterial peptides, 8 of which had biological activity and stimulated MBP(85-99)-specific T-cell clones.…”

Section: Ms In Humansmentioning

confidence: 99%

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Theiler's Virus Infection: a Model for Multiple Sclerosis

Chang²,

et al. 2004

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Both genetic background and environmental factors, very probably viruses, appear to play a role in the etiology of multiple sclerosis (MS). Lessons from viral experimental models suggest that many different viruses may trigger inflammatory demyelinating diseases resembling MS. Theiler's virus, a picornavirus, induces in susceptible strains of mice early acute disease resembling encephalomyelitis followed by late chronic demyelinating disease, which is one of the best, if not the best, animal model for MS. During early acute disease the virus replicates in gray matter of the central nervous system but is eliminated to very low titers 2 weeks postinfection. Late chronic demyelinating disease becomes clinically apparent approximately 2 weeks later and is characterized by extensive demyelinating lesions and mononuclear cell infiltrates, progressive spinal cord atrophy, and axonal loss. Myelin damage is immunologically mediated, but it is not clear whether it is due to molecular mimicry or epitope spreading. Cytokines, nitric oxide/reactive nitrogen species, and costimulatory molecules are involved in the pathogenesis of both diseases. Close similarities between Theiler's virus-induced demyelinating disease in mice and MS in humans, include the following: major histocompatibility complex-dependent susceptibility; substantial similarities in neuropathology, including axonal damage and remyelination; and paucity of T-cell apoptosis in demyelinating disease. Both diseases are immunologically mediated. These common features emphasize the close similarities of Theiler's virus-induced demyelinating disease in mice and MS in humans

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Section: Cytotoxic T Lymphocytescontrasting

confidence: 66%

Section: Tmev-induced Disease In Susceptible Micementioning

confidence: 99%

Section: Ms In Humansmentioning

confidence: 99%

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Theiler's Virus Infection: a Model for Multiple Sclerosis

Chang²,

et al. 2004

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“…Disruption of IL-6 in normally resistant H-2 b mice had no effect on virus-induced injury of neurons. These mice cleared the virus infection normally, likely as a result of a vigorous antiviral class I-restricted cytotoxic lymphocyte response (Borson et al, 1997;Dethlefs et al, 1997). In contrast, when we crossed IL-6-deficient mice with susceptible H-2 q mice, these animals showed early death and prominent infection in the gray matter of the spinal cord.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 Protects Anterior Horn Neurons from Lethal Virus-Induced Injury

et al. 2003

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We evaluated the role of interleukin-6 (IL-6) in neuronal injury after CNS infection. IL-6-/- and IL-6+/+ mice of resistant major histocompatibility complex (MHC) H-2b haplotype intracerebrally infected with Theiler's virus cleared the infection normally without development of viral persistence, lethal neuronal infection, or late phase demyelination. In contrast, infection of IL-6-/- mice on a susceptible H-2q haplotype resulted in frequent deaths and severe neurologic deficits within 2 weeks of infection as compared with infected IL-6+/+ H-2q littermate controls. Morphologic analysis demonstrated dramatic injury to anterior horn neurons of IL-6-/- H-2q mice at 12 d after infection. Infectious viral titers in the CNS (brain and spinal cord combined) were equivalent between IL-6-/- H-2q and IL-6+/+ H-2q mice. In contrast, more viral RNA was detected in the spinal cord of IL-6-/- mice compared with IL-6+/+ H-2q mice. Virus antigen was localized predominantly to anterior horn cells in infected IL-6-/- H-2q mice. IL-6 deletion did not affect the humoral response directed against virus, nor did it affect the expression of CD4, CD8, MHC class I, or MHC class II in the CNS. Importantly, IL-6 was expressed by astrocytes of infected IL-6+/+ mice but not in astrocytes of IL-6-/- mice or uninfected IL-6+/+ mice. Furthermore, expression of various chemokines was robust at 12 d after infection in both H-2b and H-2q IL-6-/- mice, indicating that intrinsic CNS inflammatory responses did not depend on the presence of IL-6. Finally, in vitro analysis of virus-induced death in neuroblastoma-spinal cord-34 motor neurons and primary anterior horn cell neurons showed that IL-6 exerted a neuroprotective effect. These data support the hypothesis that IL-6 plays a critical role in protecting specific populations of neurons from irreversible injury.

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“…Immunological crossreaction between different strains of the same virus is extremely common -influenza A, coronaviruses, hepatitis E virus and HIV-1 and HIV-2 are but a few examples [10][11][12][13][14][15][16][17] . Indeed, HIV-2 was identified precisely because, using western blots, sera lacked reactivity to the HIV-1 surface envelope protein.…”

Section: Crossreactivitymentioning

confidence: 99%