Mechanisms of Viral Interference with MHC Class I Antigen Processing and Presentation¹

Viruses are ubiquitous and dangerous obligate intracellular parasites. To facilitate recognition of virus-infected cells by the immune system, vertebrates evolved a system that displays oligopeptides derived from viral proteins on the surface of cells in association with class I molecules of the major histocompatibility complex. Here we review the mechanisms counter-evolved by viruses to interfere with the generation of viral peptides, their intracellular trafficking, or the cell surface expression of class I molecules bearing viral peptides. This topic is important in its own right because the viruses that encode these proteins represent medically important pathogens, are potential vectors for vaccines or gene therapy, and provide strategies and tools for blocking immune recognition in transplantation, autoimmunity, and gene therapy. In addition, studies on viral interference provide unique insights into unfettered antigen processing and normal cellular functions that are exploited and exaggerated by viruses.