Vaccinia virus encodes a previously uncharacterized mitochondrial-associated inhibitor of apoptosis.
To circumvent apoptotic death, many viruses encode Bcl-2 homologous proteins that function at the mitochondria. Vaccinia virus, the prototypic member of the Poxviridae family, does not encode a Bcl-2 homolog but inhibits the mitochondrial arm of the apoptotic cascade by an unknown mechanism. We now report that F1L, a previously unidentified protein in vaccinia virus, is responsible for the inhibition of apoptosis. Cells infected with vaccinia virus are resistant to staurosporine-mediated cleavage of poly(ADP-ribose) polymerase, caspases 3 and 9, and release of cytochrome c. In contrast, a vaccinia virus deletion mutant, VV811, was unable to inhibit apoptosis; however, the antiapoptotic function was restored by expression of the F1L ORF, which is absent in VV811. Although F1L displays no homology to members of the Bcl-2 family, it localizes to the mitochondria through a C-terminal hydrophobic domain. We show that expression of F1L interferes with apoptosis by inhibiting the loss of the inner mitochondrial membrane potential and the release of cytochrome c.
Wasilenko
Shawn T
ST
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada T6G 2S2.
Stewart
Tara L
TL
Meyers
Adrienne F A
AF
Barry
Michele
M
D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D045304:Cytochromes c / Q000096:biosynthesis; D004279:DNA, Viral / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008928:Mitochondria / Q000502:physiology; D016366:Open Reading Frames; D017384:Sequence Deletion; D019311:Staurosporine / Q000494:pharmacology; D014616:Vaccinia virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D004279:DNA, Viral; D014764:Viral Proteins; D045304:Cytochromes c; D019311:Staurosporine