Vaccinia Virus Encodes a Previously Uncharacterized Mitochondrial-Associated Inhibitor of Apoptosis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 100; no. 24; pp. 14345 - 14350
• Main Authors: Wasilenko, Shawn T., Stewart, Tara L., Adrienne F. A. Meyers, Barry, Michele
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 25.11.2003; National Acad Sciences
• Subjects: Apoptosis; Apoptosis - drug effects; Base Sequence; Biological Sciences; Cytochromes; Cytochromes c - biosynthesis; DNA, Viral - genetics; F1L protein; HeLa Cells; Humans; Infections; Jurkat Cells; Microbiology; Mitochondria; Mitochondria - physiology; Open Reading Frames; Proteins; Sequence Deletion; Staurosporine - pharmacology; T lymphocytes; Vaccinia virus; Vaccinia virus - genetics; Vaccinia virus - pathogenicity; Vaccinia virus - physiology; Viral Proteins - genetics; Viral Proteins - physiology; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2235583100

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.