A Survival Game of Hide and Seek: Cytomegaloviruses and MHC Class I Antigen Presentation Pathways

Abstract

Cytomegaloviruses (CMV) are members of the ubiquitous family of herpesviruses, which escape immunological clearance and persist throughout life in the infected host. Cytomegaloviruses have developed numerous strategies that permit them to co-exist with their host even as an anti-virus immune response endangers their long-term survival. A considerable number of these strategies are aimed at MHC class I presentation of viral proteins to CD8⁺ T cells (T_CD8+ ). Although the gamut of CMV immune evasion will be briefly examined, the primary focus of this review is on the host ability to counteract the strategies developed by CMV to inhibit antigen processing and presentation. A primary mechanism used by the immune system is the recognition of very early virus proteins including recognition of the immunomodulatory proteins themselves. We further speculate that cross-presentation of antigen is an adaptive immune response to the inhibition of direct presentation. Other mechanisms, such as the evolution of pAPC subsets, may also allow the immune system to adapt to a variety of different infectious pathogens while preventing cytopathic infection of all pAPCs.