title: Negative regulation of cytoplasmic RNA-mediated antiviral signaling.
abstract: The recent, rapid progress in our understanding of cytoplasmic RNA-mediated antiviral innate immune signaling was initiated by the discovery of retinoic acid-inducible gene I (RIG-I) as a sensor of viral RNA. It is now widely recognized that RIG-I and related RNA helicases, melanoma differentiation-associated gene-5 (MDA5) and laboratory of genetics and physiology-2 (LGP2), can initiate and/or regulate RNA and virus-mediated type I IFN production and antiviral responses. As with other cytokine systems, production of type I IFN is a transient process, and can be hazardous to the host if unregulated, resulting in chronic cellular toxicity or inflammatory and autoimmune diseases. In addition, the RIG-I-like receptor (RLR) system is a fundamental target for virus-encoded immune suppression, with many indirect and direct examples of interference described. In this article, we review the current understanding of endogenous negative regulation in RLR signaling and explore direct inhibition of RLR signaling by viruses as a host immune evasion strategy.
authors.affiliation: Department of Medicine, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Komuro
authors.forename: Darja
authors.initials: D
authors.lastname: Bamming
authors.forename: Curt M
authors.initials: CM
authors.lastname: Horvath
mesh_terms: D000818:Animals; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D016207:Cytokines / Q000502:physiology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D004268:DNA-Binding Proteins; D000074749:Deubiquitinating Enzyme CYLD; D010450:Endopeptidases / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007370:Interferon Type I / Q000096:biosynthesis*; D000072640:Interferon-Induced Helicase, IFIH1; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins / Q000502:physiology; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins / Q000502:physiology; D056971:Nuclear Receptor Co-Repressor 1; D019696:Peptidylprolyl Isomerase / Q000502:physiology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology; D020365:RNA Helicases / Q000502:physiology; D012367:RNA, Viral / Q000032:analysis*; D012097:Repressor Proteins / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D025841:Small Ubiquitin-Related Modifier Proteins / Q000502:physiology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D025521:Tumor Suppressor Proteins / Q000502:physiology; D014452:Ubiquitins / Q000502:physiology
chemical_list: C466624:ATG12 protein, human; C502778:ATG5 protein, human; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D016207:Cytokines; D004268:DNA-Binding Proteins; D007370:Interferon Type I; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; C539127:NCOR1 protein, human; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C527006:NLRX1 protein, human; C539128:Ncor1 protein, mouse; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D012367:RNA, Viral; D012097:Repressor Proteins; C506822:SIKE protein, mouse; D025841:Small Ubiquitin-Related Modifier Proteins; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; C074034:ISG15 protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C023132:glycerone kinase; C520569:DHX58 protein, human; D010450:Endopeptidases; C525076:OTUD5 protein, human; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; C503356:Ddx58 protein, mouse; C510592:Ifih1 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse