title: Ectromelia virus encodes a family of Ankyrin/F-box proteins that regulate NFκB.
abstract: A notable feature of poxviruses is their ability to inhibit the antiviral response, including the nuclear factor kappa B (NFκB) pathway. NFκB is a transcription factor that is sequestered in the cytoplasm until cell stimulation, and relies on the SCF (Skp1, culllin-1, F-box) ubiquitin ligase to target its inhibitor, IκBα, for degradation. IκBα is recruited to the SCF by the F-box domain-containing protein βTrCP. Here, we show that ectromelia virus, the causative agent of mousepox, encodes four F-box-containing proteins, EVM002, EVM005, EVM154, and EVM165, all of which contain Ankyrin (Ank) domains. The Ank/F-box proteins inhibit NFκB nuclear translocation, and this inhibition is dependent on the F-box domain. We also demonstrate that EVM002, EVM005, EVM154, and EVM165 prevent IκBα degradation, suggesting that they target the SCF. This study identifies a new mechanism by which ectromelia virus inhibits NFκB.
authors.affiliation: Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, 6-020 Katz Group Center, Edmonton, Alberta, Canada, T6G 2E1. Electronic address: burles@ualberta.ca.
authors.forename: Kristin
authors.initials: K
authors.lastname: Burles
authors.affiliation: Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, 6-020 Katz Group Center, Edmonton, Alberta, Canada, T6G 2E1.
authors.forename: Nicholas
authors.initials: N
authors.lastname: van Buuren
authors.affiliation: Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, 6-020 Katz Group Center, Edmonton, Alberta, Canada, T6G 2E1.
authors.forename: Michele
authors.initials: M
authors.lastname: Barry
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004481:Ectromelia virus / Q000235:genetics / Q000378:metabolism*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D016328:NF-kappa B / Q000378:metabolism*; D010957:Plasmids; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017487:Ankyrins; D044783:F-Box Proteins; D016328:NF-kappa B; D014764:Viral Proteins; D044843:SKP Cullin F-Box Protein Ligases; D051550:I-kappa B Kinase
keywords: Ankyrin; EVM002; EVM005; EVM154; EVM165; Ectromelia virus; F-box; NFκB; Poxvirus