Negative regulators of the RIG-I-like receptor signaling pathway

• Type of Material: Article
• Authors: Kendra Quicke, Emory University; Michael S. Diamond, Washington University; Mehul S. Suthar, Emory University
• Language: English
• Date: 2017-04-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
• Final Published Version (URL): http://dx.doi.org/10.1002/eji.201646484
• Title of Journal or Parent Work: European Journal of Immunology
• ISSN: 0014-2980
• Volume: 47
• Issue: 4
• Start Page: 615
• End Page: 628
• Grant/Funding Information: The Diamond laboratory is funded in part by the National Institutes of Health grants U19AI083019, R01AI104002 and R01AI074973.; The Suthar laboratory is funded in part by National Institutes of Health grants U19AI083019, R56AI110516, R21AI113485, 2U19AI090023, Emory University Department of Pediatrics Junior Faculty Focused Award, CCIV Pilot awards, Children’s Healthcare of Atlanta, Emory Vaccine Center, and the Georgia Research Alliance.
• Keywords: INNATE IMMUNITY; INDUCIBLE GENE-I; HEPATITIS-C VIRUS; NF-KAPPA-B; Innate response; MAVS; RIG-I; INTERFERON-PRODUCTION; Negative regulation; RNA HELICASE LGP2; Immunology; ANTIVIRAL IMMUNE-RESPONSES; MDA5; ENDOPLASMIC-RETICULUM; Life Sciences & Biomedicine; UBIQUITIN LIGASE; CYTOKINE STORM; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, General

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.