Cowpox virus evades CTL recognition and inhibits the intracellular transport of MHC class I molecules

Anindya Dasgupta, Erika Hammarlund, Mark K. Slifka, Klaus Früh

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Orthopoxviruses evade host immune responses by using a number of strategies, including decoy chemokine receptors, regulation of apoptosis, and evasion of complement-mediated lysis. Diferent from other poxviral subfamilies, however, orthopoxviruses are not known to evade recognition by CTL. In fact, vaccinia virus (VV) is used as a vaccine against smallpox and a vector for eliciting strong T cell responses to foreign Ags. and both human and mouse T cells are readily stimulated by VV-infected APC in vitro. Surprisingly, however, CD8+ T cells of mice infected with cowpox virus (CPV) or VV recognized APC infected with VV but not APC infected with CPV. Likewise, CD8+ T cells from vaccinated human subjects could not be activated by CPV-infected targets and CPV prevented the recognition of VV-infected APC upon coinfection. Because CD8+ T cells recognize viral peptides presented by MHC class I (MHC I), we examined surface expression, total levels, and intracellular maturation of MHC I in CPV- and VV-infected human and mouse cells. Although total levels of MHC I were unchanged, CPV reduced surface levels and inhibited the intracellular transport of MHC I early during infection. CPV did not prevent peptide loading of MHC I but completely inhibited MHC I exit from the endoplasmic reticulam. Because this inhibition was independent of viral replication, we conclude that an early gene product of CPV abrogates MHC I trafficking, thus rendering CPV-iefected cells "invisible" to T cells. The absence of this immune evasion mechanism in VV likely limits virulence without compromising immunogenicity.

Original languageEnglish (US)
Pages (from-to)1654-1661
Number of pages8
JournalJournal of Immunology
Volume178
Issue number3
DOIs
StatePublished - Feb 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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