title: Foreign RNA induces the degradation of mitochondrial antiviral signaling protein (MAVS): the role of intracellular antiviral factors.
abstract: Mitochondrial antiviral signaling protein (MAVS) is an essential adaptor molecule that is responsible for antiviral signaling triggered by retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), leading to the induction of type I interferon in innate immunity. Previous studies have shown that certain viruses evade the innate immune response by cleaving the MAVS protein. However, little is known about how MAVS is regulated in response to foreign RNA, including both single-stranded (ss) and double-stranded (ds) RNA, because most previous reports have shown that the cleavage of MAVS is executed by proteases that are induced or activated by the invading RNA viruses. Here, we report that MAVS mRNA is degraded in response to polyinosinic-polycytidylic acid (polyI:C), a synthetic dsRNA, in A549 cells. RNA interference (RNAi) experiments revealed that both ssRNA- and dsRNA-associated pattern-recognition receptors (PRRs) were not involved in the degradation of MAVS mRNA. Foreign RNA also induced the transient degradation of the MAVS protein. In the resting state, the MAVS protein was protected from degradation by interferon regulatory factor 3 (IRF3); moreover, the dimerization of IRF3 appeared to be correlated with the rescue of protein degradation in response to polyI:C. The overexpression of MAVS enhanced interferon-β (IFN-β) expression in response to polyI:C, suggesting that the degradation of MAVS contributes to the suppression of the hyper-immune reaction in late-phase antiviral signaling. Taken together, these results suggest that the comprehensive regulation of MAVS in response to foreign RNA may be essential to antiviral host defenses.
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Fei
authors.initials: F
authors.lastname: Xing
authors.forename: Tomoh
authors.initials: T
authors.lastname: Matsumiya
authors.forename: Koji
authors.initials: K
authors.lastname: Onomoto
authors.forename: Ryo
authors.initials: R
authors.lastname: Hayakari
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yoneyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujita
authors.forename: Kei
authors.initials: K
authors.lastname: Satoh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000998:Antiviral Agents / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D020011:Protective Agents / Q000378:metabolism; D055550:Protein Stability / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D012313:RNA / Q000378:metabolism*; D020871:RNA Stability / Q000187:drug effects / Q000235:genetics; D012328:RNA Viruses / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D051193:Toll-Like Receptors / Q000378:metabolism; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000998:Antiviral Agents; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C505371:MAVS protein, human; D020011:Protective Agents; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D012313:RNA; D016899:Interferon-beta; D011070:Poly I-C