title: Negative regulators of the RIG-I-like receptor signaling pathway.
abstract: Upon recognition of specific molecular patterns on microbes, host cells trigger an innate immune response, which culminates in the production of type I interferons, proinflammatory cytokines and chemokines, and restricts pathogen replication and spread within the host. At each stage of this response, there are stimulatory and inhibitory signals that regulate the magnitude, quality, and character of the response. Positive regulation promotes an antiviral state to control and eventually clear infection, whereas negative regulation dampens inflammation and prevents immune-mediated tissue damage. An overexuberant innate response can lead to cell and tissue destruction, and the development of spontaneous autoimmunity. The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), RIG-I and melanoma differentiation-associated gene 5 (MDA5), belong to a family of cytosolic host RNA helicases that recognize distinct nonself RNA signatures and trigger innate immune responses against several RNA viruses by signaling through the essential adaptor protein mitochondrial antiviral signaling (MAVS). The RLR signaling pathway is tightly regulated to maximize antiviral immunity and minimize immune-mediated pathology. This review highlights contemporary findings on negative regulators of the RLR signaling pathway, with specific focus on the proteins and biological processes that directly regulate RIG-I, MDA5 and MAVS signaling function.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.|Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA, USA.
authors.forename: Kendra M
authors.initials: KM
authors.lastname: Quicke
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.|Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.|Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.|Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.|Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA, USA.
authors.forename: Mehul S
authors.initials: MS
authors.lastname: Suthar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D000071457:DEAD Box Protein 58 / Q000378:metabolism*; D025461:Feedback, Physiological; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology*; D000072640:Interferon-Induced Helicase, IFIH1 / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D015398:Signal Transduction; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human; D012313:RNA; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D000072640:Interferon-Induced Helicase, IFIH1
keywords: Innate response; MAVS; MDA5; Negative regulation; RIG-I