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RNA helicase signaling is critical for type i interferon production and protection against Rift Valley fever virus during mucosal challenge.

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.
AuthorsMegan E Ermler, Ekaterina Yerukhim, Jill Schriewer, Stefan Schattgen, Zachary Traylor, Adam R Wespiser, Daniel R Caffrey, Zhijian J Chen, Charles H King, Michael Gale Jr, Marco Colonna, Katherine A Fitzgerald, R Mark L Buller, Amy G Hise
JournalJournal of virology (J Virol) Vol. 87 Issue 9 Pg. 4846-60 (May 2013) ISSN: 1098-5514 [Electronic] United States
PMID23408632 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Toll-Like Receptors
  • Interferon-beta
  • Ddx58 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
Topics
  • Animals
  • Cell Line
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases (genetics, immunology)
  • Dendritic Cells (immunology, virology)
  • Female
  • Humans
  • Interferon-beta (genetics, immunology)
  • Macrophages (immunology, virology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout (genetics)
  • Mucous Membrane (immunology, virology)
  • Rift Valley Fever (enzymology, immunology, prevention & control, virology)
  • Rift Valley fever virus (physiology)
  • Signal Transduction
  • Toll-Like Receptors (genetics, immunology)

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