Interaction of Bunyamwera orthobunyavirus NSs protein with Mediator protein MED8: a mechanism for inhibiting the interferon response.

VHJ Leonard, A Kohl, TJ Hart, Richard Michael Elliott

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)9667-9675
Number of pages9
JournalJournal of Virology
Volume80
Issue number19
DOIs
Publication statusPublished - Oct 2006

Keywords

  • RNA-POLYMERASE-II
  • C-TERMINAL DOMAIN
  • FEVER VIRUS
  • TRANSCRIPTIONAL ACTIVATION
  • NUCLEAR RECEPTORS
  • SRB MEDIATOR
  • P-TEFB
  • COMPLEXES
  • VALLEY
  • YEAST

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