The immunodominant CD8+ T cell epitope region of Theiler's virus in resistant C57BL/6 mice is critical for anti-viral immune responses, viral persistence, and binding to the host cells

Jinjong Myoung, Wanqiu Hou, Bongsu Kang, Michael A. Lyman, Jeong Ah Kang, Byung S Kim*

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Theiler's virus infection induces an immune-mediated demyelinating disease, providing a relevant animal model of human multiple sclerosis. VP2121-130-specific CD8+ T cells in resistant H-2b mice account for the majority of CNS-infiltrating CD8+ T cells. To further study the role of the CD8+ T cells, we generated a panel of mutant viruses substituted with L, G, or T at the anchor residue (M130) of the VP2121-130 epitope. M130L virus (M130L-V) with a substitution of M with L displayed similar properties as wild-type virus (WT-V). However, M130G-V and M130T-V could not establish a persistent infection in the CNS. The level of both virus-specific CD8+ and CD4+ T cell responses is significantly reduced in mice infected with these variant viruses. While all mutant and wild-type viruses replicate comparably in BHK cells, replication of M130G-V and M130T-V in macrophages was significantly lower compared to those infected with WT-V and M130L-V. Interestingly, these mutant viruses deficient in replication in primary mouse cells showed drastically reduced binding ability to the cells. These results suggest that the anchor residue of the predominant CD8+ T cell epitope of TMEV in resistant mice is critical for the virus to infect target cells and this deficiency may result in poor viral persistence leading to correspondingly low T cell responses in the periphery and CNS. Thus, selection of the cellular binding region of the virus as the predominant epitope for CD8+ T cells in resistant mice may provide a distinct advantage in controlling viral persistence by preventing escape mutations.

Original languageEnglish (US)
Pages (from-to)159-171
Number of pages13
JournalVirology
Volume360
Issue number1
DOIs
StatePublished - Mar 30 2007

Keywords

  • CD8 T cells
  • CNS
  • Epitope
  • Mutant viruses
  • TMEV

ASJC Scopus subject areas

  • Virology

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