Cowpox Virus Inhibits the Transporter Associated with Antigen Processing to Evade T Cell Recognition

Dina Alzhanova, David M. Edwards, Erika Hammarlund, Isabel G. Scholz, Daniëlle Horst, Mary J. Wagner, Chris Upton, Emmanuel J. Wiertz, Mark K. Slifka, Klaus Früh

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Cowpox virus encodes an extensive array of putative immunomodulatory proteins, likely contributing to its wide host range, which includes zoonotic infections in humans. Unlike Vaccinia virus, cowpox virus prevents stimulation of CD8+ T cells, a block that correlated with retention of MHC class I in the endoplasmic reticulum by the cowpox virus protein CPXV203. However, deletion of CPXV203 did not restore MHC class I transport or T cell stimulation. Here, we demonstrate the contribution of an additional viral protein, CPXV12, which interferes with MHC class I/peptide complex formation by inhibiting peptide translocation by the transporter associated with antigen processing (TAP). Importantly, human and mouse MHC class I transport and T cell stimulation was restored upon deletion of both CPXV12 and CPXV203, suggesting that these unrelated proteins independently mediate T cell evasion in multiple hosts. CPXV12 is a truncated version of a putative NK cell ligand, indicating that poxviral gene fragments can encode new, unexpected functions.

Original languageEnglish (US)
Pages (from-to)433-445
Number of pages13
JournalCell Host and Microbe
Volume6
Issue number5
DOIs
StatePublished - Nov 19 2009

Keywords

  • CELLBIO
  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Alzhanova, D., Edwards, D. M., Hammarlund, E., Scholz, I. G., Horst, D., Wagner, M. J., Upton, C., Wiertz, E. J., Slifka, M. K., & Früh, K. (2009). Cowpox Virus Inhibits the Transporter Associated with Antigen Processing to Evade T Cell Recognition. Cell Host and Microbe, 6(5), 433-445. https://doi.org/10.1016/j.chom.2009.09.013