Cowpox virus evades CTL recognition and inhibits the intracellular transport of MHC class I molecules.
Orthopoxviruses evade host immune responses by using a number of strategies, including decoy chemokine receptors, regulation of apoptosis, and evasion of complement-mediated lysis. Different 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 reticulum. Because this inhibition was independent of viral replication, we conclude that an early gene product of CPV abrogates MHC I trafficking, thus rendering CPV-infected cells "invisible" to T cells. The absence of this immune evasion mechanism in VV likely limits virulence without compromising immunogenicity.
Dasgupta
Anindya
A
Oregon Health and Science University, Vaccine and Gene Therapy Institute, Beaverton, OR 97006, USA.
Hammarlund
Erika
E
Slifka
Mark K
MK
Früh
Klaus
K
D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D002478:Cells, Cultured; D015605:Cowpox / Q000276:immunology; D015608:Cowpox virus / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D021381:Protein Transport / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014615:Vaccinia / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I