title: 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.
authors: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA.
authors: Megan E
authors: ME
authors: Ermler
authors: Ekaterina
authors: E
authors: Yerukhim
authors: Jill
authors: J
authors: Schriewer
authors: Stefan
authors: S
authors: Schattgen
authors: Zachary
authors: Z
authors: Traylor
authors: Adam R
authors: AR
authors: Wespiser
authors: Daniel R
authors: DR
authors: Caffrey
authors: Zhijian J
authors: ZJ
authors: Chen
authors: Charles H
authors: CH
authors: King
authors: Michael
authors: M
authors: Gale
authors: Marco
authors: M
authors: Colonna
authors: Katherine A
authors: KA
authors: Fitzgerald
authors: R Mark L
authors: RM
authors: Buller
authors: Amy G
authors: AG
authors: Hise
mesh_terms: D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology*; D012295:Rift Valley Fever / Q000201:enzymology* / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D012296:Rift Valley fever virus / Q000502:physiology*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology
chemical_list: D051193:Toll-Like Receptors; D016899:Interferon-beta; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases