The CD4-mediated immune response is critical in determining the outcome of infection using Theiler's viruses with VP1 capsid protein point mutations

M. Rodriguez, R. P. Roos, D. McGavern, L. Zoecklein, K. Pavelko, H. Sang, X. Lin

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Daniel's strain of Theiler's virus (DA) induces a chronic demyelinating disease in the central nervous system (CNS) of susceptible SJL mice, which serves as an excellent model of multiple sclerosis. We previously demonstrated that point mutations near a putative virus receptor-binding site [VP1 99 (Gly to Ser) or 100 (Gly to Asp)] totally attenuate the ability of DA to persist and induce demyelination in SJL mice. The current studies demonstrate that class II-restricted CD4+ T cells play a major role in clearing VP1 mutant DA viruses from the CNS to prevent demyelination. Infection of SJL CD4((-/-)) mice with DA-VP1-99(Ser) or DA-VP1-100(Asp) resulted in virus persistence and prominent demyelination in the spinal cord. In contrast, infection of SJL CD8((-/-)) mice with DA-VP1-99(Ser) or DA-VP1-100 did not result in virus persistence or demyelination. In addition, no virus-specific cytotoxicity was observed in CNS-infiltrating lymphocytes following infection of SJL mice with VP1 mutant viruses. The mutant DA-VP1-99(Ser) and DA-VP1(100) viruses were in fact neurovirulent when compared to the wild-type DA virus, as they induced an overwhelming encephalitis and early lethality (2 to 4 days postinfection) in mice deficient in the IFN-α/β receptor. Therefore, the nondemyelinating phenotype observed with DA-VP1-99(Ser) and DA-VP1-100(Asp) viruses is dependent in part on the CD4-mediated host immune response. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)9-19
Number of pages11
JournalVirology
Volume275
Issue number1
DOIs
StatePublished - Sep 15 2000

ASJC Scopus subject areas

  • Virology

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