Prevention of Cellular Suicide by Cytomegaloviruses 英文参考文献.docVIP

Viruses 2012, 4, 1928-1949; doi:10.3390/v4101928 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Prevention of Cellular Suicide by Cytomegaloviruses Patricia M. Fliss and Wolfram Brune * Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistr. 52, 20251 Hamburg, Germany; E-Mail: patricia.fliss@hpi.uni-hamburg.de * Author to whom correspondence should be addressed; E-Mail: wolfram.brune@hpi.uni-hamburg.de; Tel.: +49-40-48051-351. Received: 31 August 2012; in revised form: 21 September 2012 / Accepted: 25 September 2012 / Published: 2 October 2012 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. Keywords: HCMV; UL36;