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

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.

SUBMITTER: Byun M

PROVIDER: S-EPMC2791900 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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

Byun Minji M Verweij Marieke C MC Pickup David J DJ Wiertz Emmanuel J H J EJ Hansen Ted H TH Yokoyama Wayne M WM

Cell host & microbe 20091101 5

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 ...[more]

PMID: 19917497

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

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

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