Mutual antagonism between the ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome

Priya Luthra, Parameshwaran Ramanan, Chad E. Mire, Carla Weisend, Yoshimi Tsuda, Benjamin Yen, Gai Liu, Daisy W. Leung, Thomas W. Geisbert, Hideki Ebihara, Gaya K. Amarasinghe, Christopher F. Basler

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105 Scopus citations

Abstract

The cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and induces type I IFN responses to control viral replication. The cellular dsRNA binding protein PACT can also activate RIG-I. To counteract innate antiviral responses, some viruses, including Ebola virus (EBOV), encode proteins that antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT. In addition, PACT-VP35 interaction impairs the association between VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and modulating EBOV replication. PACT-deficient cells are defective in IFN induction and are insensitive to VP35 function. These data support a model in which the VP35-PACT interaction is mutually antagonistic and plays a fundamental role in determining the outcome of EBOV infection.

Original languageEnglish (US)
Pages (from-to)74-84
Number of pages11
JournalCell Host and Microbe
Volume14
Issue number1
DOIs
StatePublished - Jul 17 2013

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Cite this

Luthra, P., Ramanan, P., Mire, C. E., Weisend, C., Tsuda, Y., Yen, B., Liu, G., Leung, D. W., Geisbert, T. W., Ebihara, H., Amarasinghe, G. K., & Basler, C. F. (2013). Mutual antagonism between the ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome. Cell Host and Microbe, 14(1), 74-84. https://doi.org/10.1016/j.chom.2013.06.010