Two Mechanistically Distinct Immune Evasion Proteins of Cowpox Virus Combine to Avoid Antiviral CD8 T Cells

Minji Byun, Marieke C. Verweij, David J. Pickup, Emmanuel J.H.J. Wiertz, Ted H. Hansen, Wayne M. Yokoyama

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Downregulation of MHC class I on the cell surface is an immune evasion mechanism shared by many DNA viruses, including cowpox virus. Previously, a cowpox virus protein, CPXV203, was shown to downregulate MHC class I. Here we report that CPXV12 is the only other MHC class I-regulating protein of cowpox virus and that it uses a mechanism distinct from that of CPXV203. Whereas CPXV203 retains fully assembled MHC class I by exploiting the KDEL-mediated endoplasmic reticulum retention pathway, CPXV12 binds to the peptide-loading complex and inhibits peptide loading on MHC class I molecules. Viruses deleted of both CPXV12 and CPXV203 demonstrated attenuated virulence in a CD8 T cell-dependent manner. These data demonstrate that CPXV12 and CPXV203 proteins combine to ablate MHC class I expression and abrogate antiviral CD8 T cell responses.

Original languageEnglish
Pages (from-to)422-432
Number of pages11
JournalCell Host and Microbe
Volume6
Issue number5
DOIs
StatePublished - Nov 19 2009

Keywords

  • CELLBIO
  • MICROBIO
  • MOLIMMUNO

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