title: Ectromelia virus virulence factor p28 acts upstream of caspase-3 in response to UV light-induced apoptosis.
abstract: Ectromelia virus (EV) virulence factor p28 (EVp28) is a member of a family of poxvirus proteins that are defined largely by the presence of a C-terminal RING finger motif and localization to virus factories within the cytoplasm of infected cells. Previously, overexpression of the Shope fibroma virus (SFV) homologue, N1R, in vaccinia virus (VV)-infected BGMK cells was found to inhibit virus-induced apoptosis. Here, we report that both EVp28 and overexpression of SFV N1R in poxvirus-infected HeLa cells protect specifically from UV light-induced apoptosis, but not from apoptosis induced by Fas or TNF. Further, we report that both VV and EV protect from apoptosis induced by UV, Fas and TNF. Immunoblot analysis indicates that EVp28 acts upstream of caspase-3, blocking activation of the protease in response to UV irradiation. Although no difference was found in replication of an EVp28(-) mutant virus, which expresses a truncated p28 protein lacking the RING motif, compared to EV wild-type in HeLa cells, UV irradiation of infected HeLa cells reduced the replication of the EV mutant compared with wild-type EV.
authors.affiliation: Departments of Biochemistry and Microbiology and Biology, University of Victoria, PO Box 3055, Victoria, BC, Canada V8W 3P6.
authors.forename: D J
authors.initials: DJ
authors.lastname: Brick
authors.forename: R D
authors.initials: RD
authors.lastname: Burke
authors.forename: A A
authors.initials: AA
authors.lastname: Minkley
authors.forename: C
authors.initials: C
authors.lastname: Upton
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004481:Ectromelia virus / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D015398:Signal Transduction; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D014764:Viral Proteins; C407905:virulence factor p28, Ectromelia virus; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases