title: Ectromelia virus encodes an anti-apoptotic protein that regulates cell death.
abstract: Apoptosis serves as a powerful defense against damaged or pathogen-infected cells. Since apoptosis is an effective defense against viral infection, many viruses including poxviruses, encode proteins to prevent or delay apoptosis. Here we show that ectromelia virus, the causative agent of mousepox encodes an anti-apoptotic protein EVM025. Here we demonstrate that expression of functional EVM025 is crucial to prevent apoptosis triggered by virus infection and staurosporine. We demonstrate that the expression of EVM025 prevents the conformational activation of the pro-apoptotic proteins Bak and Bax, allowing the maintenance of mitochondrial membrane integrity upon infection with ECTV. Additionally, EVM025 interacted with intracellular Bak. We were able to demonstrate that EVM025 ability to inhibit Bax activation is a function of its ability to inhibit the activity of an upstream BH3 only protein Bim. Collectively, our data indicates that EVM025 inhibits apoptosis by sequestering Bak and inhibiting the activity of Bak and Bax.
authors.affiliation: Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Ninad
authors.initials: N
authors.lastname: Mehta
authors.affiliation: Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Taylor
authors.affiliation: Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Douglas
authors.initials: D
authors.lastname: Quilty
authors.affiliation: Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: michele.barry@ualberta.ca.
authors.forename: Michele
authors.initials: M
authors.lastname: Barry
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004481:Ectromelia virus / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006801:Humans; D051379:Mice; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D014764:Viral Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
keywords: Anti-apoptosis; BH-3 only; Bax and Bak; EVM025; Ectromelia virus; F1L; Poxvirus