Two mechanistically distinct immune evasion proteins of cowpox virus combine to avoid antiviral CD8 T cells.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Byun, M; Verweij, MC; Pickup, DJ; Wiertz, EJHJ; Hansen, TH; Yokoyama, WM

Published Date

  • November 19, 2009

Published In

Volume / Issue

  • 6 / 5

Start / End Page

  • 422 - 432

PubMed ID

  • 19917497

Pubmed Central ID

  • 19917497

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2009.09.012

Language

  • eng

Conference Location

  • United States