title: Prevention of cellular suicide by cytomegaloviruses.
abstract: As intracellular parasites, viruses rely on many host cell functions to ensure their replication. The early induction of programmed cell death (PCD) in infected cells constitutes an effective antiviral host mechanism to restrict viral spread within an organism. As a countermeasure, viruses have evolved numerous strategies to interfere with the induction or execution of PCD. Slowly replicating viruses such as the cytomegaloviruses (CMVs) are particularly dependent on sustained cell viability. To preserve viability, the CMVs encode several viral cell death inhibitors that target different key regulators of the extrinsic and intrinsic apoptosis pathways. The best-characterized CMV-encoded inhibitors are the viral inhibitor of caspase-8-induced apoptosis (vICA), viral mitochondrial inhibitor of apoptosis (vMIA), and viral inhibitor of Bak oligomerization (vIBO). Moreover, a viral inhibitor of RIP-mediated signaling (vIRS) that blocks programmed necrosis has been identified in the genome of murine CMV (MCMV), indicating that this cell death mode is a particularly important part of the antiviral host response. This review provides an overview of the known cell death suppressors encoded by CMVs and their mechanisms of action.
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistr. 52, 20251 Hamburg, Germany. patricia.fliss@hpi.uni-hamburg.de
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Fliss
authors.forename: Wolfram
authors.initials: W
authors.lastname: Brune
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002470:Cell Survival; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000378:metabolism / Q000821:virology; D059865:Endoplasmic Reticulum Stress; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000821:virology*; D009336:Necrosis / Q000821:virology; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D053585:Virus Attachment; D014779:Virus Replication
chemical_list: D051017:Apoptosis Regulatory Proteins; C078035:UL36 protein, Human herpesvirus 1; D014764:Viral Proteins; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C485615:Ripk3 protein, mouse