title: Genetic screen of a library of chimeric poxviruses identifies an ankyrin repeat protein involved in resistance to the avian type I interferon response.
abstract: Viruses must be able to resist host innate responses, especially the type I interferon (IFN) response. They do so by preventing the induction or activity of IFN and/or by resisting the antiviral effectors that it induces. Poxviruses are no exception, with many mechanisms identified whereby mammalian poxviruses, notably, vaccinia virus (VACV), but also cowpox and myxoma viruses, are able to evade host IFN responses. Similar mechanisms have not been described for avian poxviruses (avipoxviruses). Restricted for permissive replication to avian hosts, they have received less attention; moreover, the avian host responses are less well characterized. We show that the prototypic avipoxvirus, fowlpox virus (FWPV), is highly resistant to the antiviral effects of avian IFN. A gain-of-function genetic screen identified fpv014 to contribute to increased resistance to exogenous recombinant chicken alpha IFN (ChIFN1). fpv014 is a member of the large family of poxvirus (especially avipoxvirus) genes that encode proteins containing N-terminal ankyrin repeats (ANKs) and C-terminal F-box-like motifs. By binding the Skp1/cullin-1 complex, the F box in such proteins appears to target ligands bound by the ANKs for ubiquitination. Mass spectrometry and immunoblotting demonstrated that tandem affinity-purified, tagged fpv014 was complexed with chicken cullin-1 and Skp1. Prior infection with an fpv014-knockout mutant of FWPV still blocked transfected poly(I·C)-mediated induction of the beta IFN (ChIFN2) promoter as effectively as parental FWPV, but the mutant was more sensitive to exogenous ChIFN1. Therefore, unlike the related protein fpv012, fpv014 does not contribute to the FWPV block to induction of ChIFN2 but does confer resistance to an established antiviral state.
authors: Section of Virology, Faculty of Medicine, Imperial College London, St. Mary's Campus, London, United Kingdom.
authors: Karen
authors: K
authors: Buttigieg
authors: Stephen M
authors: SM
authors: Laidlaw
authors: Craig
authors: C
authors: Ross
authors: Marc
authors: M
authors: Davies
authors: Stephen
authors: S
authors: Goodbourn
authors: Michael A
authors: MA
authors: Skinner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017089:Ankyrin Repeat; D001483:Base Sequence; D002642:Chick Embryo; D002645:Chickens; D005586:Fowlpox / Q000235:genetics / Q000276:immunology* / Q000821:virology; D005587:Fowlpox virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015723:Gene Library; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D011201:Poultry Diseases / Q000235:genetics / Q000276:immunology* / Q000821:virology; D017434:Protein Structure, Tertiary; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
chemical_list: D016898:Interferon-alpha; D014764:Viral Proteins