The N-terminus of Bunyamwera orthobunyavirus NSs protein is essential for interferon antagonism.
Bunyamwera virus NSs protein is involved in the inhibition of cellular transcription and the interferon (IFN) response, and it interacts with the Med8 component of Mediator. A spontaneous mutant of a recombinant NSs-deleted Bunyamwera virus (rBUNdelNSs2) was identified and characterized. This mutant virus, termed mBUNNSs22, expresses a 21 aa N-terminally truncated form of NSs. Like rBUNdelNSs2, mBUNNSs22 is attenuated in IFN-deficient cells, and to a greater extent in IFN-competent cells. Both rBUNdelNSs2 and mBUNNSs22 are potent IFN inducers and their growth can be rescued by depleting cellular IRF3. Strikingly, despite encoding an NSs protein that contains the Med8 interaction domain, mBUNNSs22 fails to block RNA polymerase II activity during infection. Overall, our data suggest that both the interaction of NSs with Med8 and a novel unidentified function of the NSs N-terminus, seem necessary for Bunyamwera virus to counteract host antiviral responses.
van Knippenberg
Ingeborg
I
Biomedical Sciences Research Centre, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.
Carlton-Smith
Charlie
C
Biomedical Sciences Research Centre, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.
Elliott
Richard M
RM
Biomedical Sciences Research Centre, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.
D000595:Amino Acid Sequence; D001483:Base Sequence; D002042:Bunyamwera virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D002460:Cell Line; D006801:Humans; D007372:Interferons / Q000037:antagonists & inhibitors*; D056892:Mediator Complex / Q000378:metabolism; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D017384:Sequence Deletion; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D010948:Viral Plaque Assay; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014779:Virus Replication
C480227:MED8 protein, human; D056892:Mediator Complex; C423923:NSs protein, Bunyamwera bunyavirus; D017361:Viral Nonstructural Proteins; D037521:Virulence Factors; D007372:Interferons