title: RIG-I-dependent antiviral immunity is effective against an RNA virus encoding a potent suppressor of RNAi.
abstract: Nodamura virus (NoV) lethally infects suckling mice and contains a segmented positive-strand RNA genome that encodes a potent suppressor of RNA interference (RNAi). Recent studies have demonstrated immune detection and subsequent processing of NoV dsRNA replicative intermediates by the mouse RNAi machinery. However, diverse RNA viruses, including Encephalomyocarditis virus that also triggers Dicer-dependent biogenesis of viral siRNAs in mouse cells, are targeted in mammals by RIG-I-like receptors that initiate an IFN-dependent antiviral response. Using mouse embryonic fibroblasts (MEFs) for NoV infection, here we show that MEFs derived from mice knockout for RIG-I, but not those knockout for MDA5, LGP2, TLR3 or TLR7, exhibited an enhanced susceptibility to NoV. Further studies indicate that NoV infection induced an IFN-dependent antiviral response mediated by RIG-I. Our findings suggest that RIG-I directs a typical IFN-dependent antiviral response against an RNA virus capable of suppressing the RNAi response.
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Department of Plant Pathology and Microbiology, and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521, USA.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Plant Pathology and Microbiology, and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521, USA; State Key Laboratory for Agrobiotechnology and Ministry of Agriculture, Key Laboratory for Plant Pathology, China Agricultural University, Beijing 100193, China.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Plant Pathology and Microbiology, and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Plant Pathology and Microbiology, and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521, USA. Electronic address: shou-wei.ding@ucr.edu.
authors.forename: Shou-wei
authors.initials: SW
authors.lastname: Ding
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Key Laboratory of Veterinary Bioproduction and Veterinary Medicine of the Ministry of Agriculture, Zhongmu Institute of China Animal Husbandry Industry Co., Ltd, No. 156 Beiqing Road, Haidian District, Beijing 100095, China. Electronic address: vetdean@cau.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D024882:Drug Resistance, Viral; D016899:Interferon-beta / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D034622:RNA Interference; D012328:RNA Viruses / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D016899:Interferon-beta; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
keywords: NoV; RIG-I; RNAi; Type I interferons
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