Homo-oligomerization facilitates the interferon-antagonist activity of the ebolavirus VP35 protein

St Patrick Reid, Washington B. Cárdenas, Christopher F. Basler

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

We have identified a putative coiled-coil motif within the amino-terminal half of the ebolavirus VP35 protein. Cross-linking studies demonstrated the ability of VP35 to form trimers, consistent with the presence of a functional coiled-coil motif. VP35 mutants lacking the coiled-coil motif or possessing a mutation designed to disrupt coiled-coil function were defective in oligomerization, as deduced by co-immunoprecipitation studies. VP35 inhibits signaling that activates interferon regulatory factor 3 (IRF-3) and inhibits (IFN)-α/β production. Experiments comparing the ability of VP35 mutants to block IFN responses demonstrated that the VP35 amino-terminus, which retains the putative coiled-coil motif, was unable to inhibit IFN responses, whereas the VP35 carboxy-terminus weakly inhibited the activation of IFN responses. IFN-antagonist function was restored when a heterologous trimerization motif was fused to the carboxy-terminal half of VP35, suggesting that an oligomerization function at the amino-terminus facilitates an "IFN-antagonist" function exerted by the carboxy-terminal half of VP35.

Original languageEnglish (US)
Pages (from-to)179-189
Number of pages11
JournalVirology
Volume341
Issue number2
DOIs
StatePublished - Oct 25 2005

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Keywords

  • Ebolavirus VP35 protein
  • Homo-oligomerization
  • Interferon

ASJC Scopus subject areas

  • Virology

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