RNA helicase signaling is critical for type I interferon production and protection against rift valley fever virus during mucosal challenge

Megan E. Ermler, Ekaterina Yerukhim, Jill Schriewer, Stefan Schattgen, Zachary Traylor, Adam R. Wespiser, Daniel R. Caffrey, Zhijian J. Chen, Charles H. King, Jr Gale Michael, Marco Colonna, Katherine A. Fitzgerald, R. Mark L Buller, Amy G. Hise

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Rift Valley fever virus (RVFV) is an emerging RNA virus with devastating economic and social consequences. Clinically, RVFV induces a gamut of symptoms ranging from febrile illness to retinitis, hepatic necrosis, hemorrhagic fever, and death. It is known that type I interferon (IFN) responses can be protective against severe pathology; however, it is unknown which innate immune receptor pathways are crucial for mounting this response. Using both in vitro assays and in vivo mucosal mouse challenge, we demonstrate here that RNA helicases are critical for IFN production by immune cells and that signaling through the helicase adaptor molecule MAVS (mitochondrial antiviral signaling) is protective against mortality and more subtle pathology during RVFV infection. In addition, we demonstrate that Toll-like-receptor-mediated signaling is not involved in IFN production, further emphasizing the importance of the RNA cellular helicases in type I IFN responses to RVFV.

Original languageEnglish (US)
Pages (from-to)4846-4860
Number of pages15
JournalJournal of virology
Volume87
Issue number9
DOIs
StatePublished - May 1 2013

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Ermler, M. E., Yerukhim, E., Schriewer, J., Schattgen, S., Traylor, Z., Wespiser, A. R., Caffrey, D. R., Chen, Z. J., King, C. H., Gale Michael, J., Colonna, M., Fitzgerald, K. A., Buller, R. M. L., & Hise, A. G. (2013). RNA helicase signaling is critical for type I interferon production and protection against rift valley fever virus during mucosal challenge. Journal of virology, 87(9), 4846-4860. https://doi.org/10.1128/JVI.01997-12