Viral modulation of antigen presentation: manipulation of cellular targets in the ER and beyond

Summary: Viruses that establish long‐term infections in their hosts have evolved a number of methods to interfere with the activities of the innate and adaptive immune systems. Control of viral infections is achieved in part through the action of cytotoxic T lymphocytes (CTLs) that recognize cytosolically derived antigenic peptides in the context of class I major histocompatibility complex (MHC) molecules. Viral replication within host cells produces abundant proteinaceous fodder for proteasomal digestion and display by class I MHC products. Tactics that disrupt antigen‐presentation pathways and prevent the display of peptides to CD8⁺ CTLs have been favored during the course of host‐virus co‐evolution. Viral immunoevasins exploit diverse cellular processes to interfere with host antiviral functions. The study of such viral factors has uncovered novel host proteins that assist these viral factors in their task and that themselves perform important cellular functions. Here, we focus on viral immunoevasins that, together with their cellular targets, interfere with antigen‐presentation pathways. In particular, we emphasize the intersection of the cellular quality‐control machinery in the endoplasmic reticulum with the herpesvirus proteins that have co‐opted it.