Sheeppox Virus SPPV14 Encodes a Bcl-2-Like Cell Death Inhibitor That Counters a Distinct Set of Mammalian Proapoptotic Proteins
Details
Publication Year 2012-11, Volume 86, Issue #21, Page 11501-11511
Journal Title
JOURNAL OF VIROLOGY
Publication Type
Journal Article
Abstract
Many viruses express inhibitors of programmed cell death (apoptosis), thereby countering host defenses that would otherwise rapidly clear infected cells. To counter this, viruses such as adenoviruses and herpesviruses express recognizable homologs of the mammalian prosurvival protein Bcl-2. In contrast, the majority of poxviruses lack viral Bcl-2 (vBcl-2) homologs that are readily identified by sequence similarities. One such virus, myxoma virus, which is the causative agent of myxomatosis, expresses a virulence factor that is a potent inhibitor of apoptosis. In spite of the scant sequence similarity to Bcl-2, myxoma virus M11L adopts an almost identical 3-dimensional fold. We used M11L as bait in a sequence similarity search for other Bcl-2-like proteins and identified six putative vBcl-2 proteins from poxviruses. Some are potent inhibitors of apoptosis, in particular sheeppox virus SPPV14, which inhibited cell death induced by multiple agents. Importantly, SPPV14 compensated for the loss of antiapoptotic F1L in vaccinia virus and acts to directly counter the cell death mediators Bax and Bak. SPPV14 also engages a unique subset of the death-promoting BH3-only ligands, including Bim, Puma, Bmf, and Hrk. This suggests that SPPV14 may have been selected for specific biological roles as a virulence factor for sheeppox virus.
Publisher
AMER SOC MICROBIOLOGY
Keywords
PERMEABILITY TRANSITION PORE; ANTI-APOPTOTIC PROTEIN; EPSTEIN-BARR-VIRUS; KAPPA-B KINASE; MYXOMA-VIRUS; BH3-ONLY PROTEINS; PROSURVIVAL BCL-2; FOWLPOX VIRUS; PREVENTS APOPTOSIS; POXVIRUS PROTEIN
WEHI Research Division(s)
Structural Biology
Rights Notice
Copyright © 2013 by the American Society for Microbiology


Creation Date: 2012-11-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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