Interaction of Bunyamwera Orthobunyavirus NSs protein with mediator protein MED8: a mechanism for inhibiting the interferon response.
The NSs protein of Bunyamwera virus (Bunyaviridae) is an antiapoptotic interferon antagonist involved in silencing host protein expression by interfering with mRNA synthesis. Here, we show that the ability to inhibit both host transcription and the interferon response is linked to interaction of NSs with the MED8 component of Mediator, a protein complex necessary for mRNA production. The interacting domain on NSs was mapped to the C-terminal region, which contains amino acids conserved among orthobunyavirus NSs proteins. A recombinant virus in which the interacting domain in NSs was deleted had strongly reduced ability to inhibit host protein expression and was unable to inhibit the interferon response. This study provides further information on the mechanisms by which bunyavirus nonstructural proteins are involved in pathogenesis.
Léonard
Vincent H J
VH
Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 5JR, Scotland, United Kingdom.
Kohl
Alain
A
Hart
Timothy J
TJ
Elliott
Richard M
RM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007372:Interferons / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D056892:Mediator Complex; D008969:Molecular Sequence Data; D016851:Orthobunyavirus / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C480227:MED8 protein, human; D056892:Mediator Complex; D014157:Transcription Factors; D014764:Viral Proteins; D007372:Interferons; D012321:DNA-Directed RNA Polymerases