K3-mediated evasion of CD8(+) T cells aids amplification of a latent gamma-herpesvirus

Nat Immunol. 2002 Aug;3(8):733-40. doi: 10.1038/ni818. Epub 2002 Jul 8.

Abstract

The murine gamma-herpesvirus-68 (MHV-68) K3 protein, like that of the Kaposi's sarcoma associated herpesvirus, down-regulates major histocompatibility complex (MHC) class I expression. However, how this contributes to viral replication in vivo is unclear. After intranasal MHV-68 infection, K3 was transcribed both during acute lytic infection in the lung and during latency establishment in lymphoid tissue. K3-deficient viruses were not cleared more rapidly from the lung, but the number of latently infected spleen cells was reduced and the frequency of virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) was increased. CTL depletion reversed the viral latency deficit. Thus, a major function of K3 appears to be CTL evasion during viral latency expansion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Flow Cytometry
  • Gene Expression Regulation / immunology
  • Genes, MHC Class I / immunology
  • In Situ Hybridization
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mutagenesis, Insertional
  • Polymerase Chain Reaction
  • RNA, Viral / analysis
  • RNA, Viral / genetics
  • Rhadinovirus / genetics
  • Rhadinovirus / growth & development
  • Rhadinovirus / immunology*
  • Spleen / virology
  • T-Lymphocytes, Cytotoxic / immunology
  • Transcription, Genetic / immunology
  • Viral Proteins / biosynthesis
  • Viral Proteins / genetics
  • Viral Proteins / immunology*

Substances

  • RNA, Viral
  • Viral Proteins