Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules

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. 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.

Poxvirus Infection-Associated Downregulation of C-Type Lectin-Related-b Prevents NK Cell Inhibition by NK Receptor Protein-1B

“…In contrast, it remains possible that the virus (or host cell) encodes proteins to interfere specifically with Clr/Clec2 function, perhaps through direct association and trafficking by the C-type lectin-related proteins or through virally encoded proteins that drive ubiquitination (43). Poxviruses are known to employ several strategies to block expression of host proteins that are involved in activation of the immune response (44)(45)(46), and there are indications that Clr-b might be involved in immune activation, making it a target for the virus. For example, exposure of human APCs to inactivated viruses or pathogen mimetics produces a substantial increase of LLT1, a human Clr-b homolog, which may protect APCs from NK cell attack (47).…”

Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation

“…Different viral vectors may also vary in their ability to evade the host immune response. Vaccinia virus has within its genome a number of immune evasion genes which may allow it to evade clearance by CD8 ϩ T cells and allow it to persist long enough to target Ag to DCs (51), although, unlike other poxviruses, vaccinia virus does not appear to interfere with MHC class I Ag processing (52). Another alternative explanation for the ability of vaccinia virus to boost would be that VV-SYV readily replicates, whereas the Flu-ME (when given i.v.)…”

Novel Nipah Virus Immune-Antagonism Strategy Revealed by Experimental and Computational Study

“…However, the suppression of MHC-I upregulation suggests a potent deficiency in initiating the adaptive response. Suppression of antigen presentation by MHC-I is employed by multiple virus types to evade immune clearance, thereby promoting persistent infections (1,2,5,6,18,51,61). The identification of viral antigen in the brains of NiV encephalitis patients postmortem indicates the spread of the virus past the presumed respiratory route of entry (13,27).…”