Herpesviruses and immunity: The art of evasion

Abstract Herpesviruses have evolved several effective strategies to counter the host immune response. Chief among these is inhibition of the host MHC class I antigen processing and presentation pathway, thereby reducing the presentation of virus-derived epitopes on the surface of the infected cell. This review summarizes the mechanisms used by herpesviruses to achieve this goal, including shut-down of MHC class I molecule synthesis, blockage of proteasome-mediated peptide generation and prevention of TAP-mediated peptide transport. Furthermore, herpesvirus proteins can retain MHC class I molecules in the endoplasmic reticulum, or direct their retrograde translocation from the endoplasmic reticulum or endocytosis from the plasma membrane, with subsequent degradation. The resulting down-regulation of cell surface MHC class I peptide complexes thwarts the ability of cytotoxic T lymphocytes to recognize and eliminate virus-infected cells. The subversion of the natural killer cell response by herpesvirus proteins and microRNAs is also discussed.