Upon infecting a host, viruses are confronted by a coordinated and multi-faceted immune response. Indeed, evolutionary combat between virus and host has contributed signally to the host's... Show moreUpon infecting a host, viruses are confronted by a coordinated and multi-faceted immune response. Indeed, evolutionary combat between virus and host has contributed signally to the host's development of a formidable innate and adaptive immune defense arsenal, and to the virus' acquisition of effective means to evade it. Cytotoxic T lymphocytes play a key role in the elimination of virus-infected cells, which they detect through recognition of virus-derived peptides displayed at the cell surface in the context of MHC class I molecules. This highly sensitive recognition system is a prime target for immune evasion strategies deployed by many viruses, particularly large DNA viruses such as herpesviruses and poxviruses. Elucidation of the mode of action of the immune evasion proteins encoded by these viruses has not only provided new insights into viral pathogenesis, but has also led to the discovery of hitherto unknown cell biological and immunological phenomena. Moreover, viral immune evasion proteins constitute extremely useful tools to block defined stages of the MHC class I presentation pathway, not only for research purposes, but also for clinical applications. Show less
Herpesviruses stand out for their capacity to establish lifelong infections of immunocompetent hosts, generally without causing overt symptoms. Herpesviruses are equipped with sophisticated immune... Show moreHerpesviruses stand out for their capacity to establish lifelong infections of immunocompetent hosts, generally without causing overt symptoms. Herpesviruses are equipped with sophisticated immune evasion strategies, allowing these viruses to persist for life despite the presence of a strong antiviral immune response. Although viral evasion tactics appear to target virtually any stage of the innate and adaptive host immune response, detailed knowledge is now available on the molecular mechanisms underlying herpesvirus obstruction of MHC class I-restricted antigen presentation to T cells. This opens the way for clinical application. Here, we review and discuss recent efforts to exploit human herpesvirus MHC class I evasion strategies for the rational design of novel strategies for vaccine development, cancer treatment, transplant protection and gene therapy.Immunology and Cell Biology advance online publication, 8 February 2011; doi:10.1038/icb.2010.129. Show less
