TY - JOUR
T1 - Negative regulators of the RIG-I-like receptor signaling pathway
AU - Quicke, Kendra M.
AU - Diamond, Michael S.
AU - Suthar, Mehul S.
N1 - Funding Information:
The Suthar laboratory is supported in part by National Institutes of Health grants U19AI083019, R56AI110516, R21AI113485, 2U19AI090023, ORIP/OD P51OD011132, 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. The Diamond laboratory is supported in part by the National Institutes of Health grants U19AI083019, R01AI104002, and R01AI074973.
Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
KW - Innate response
KW - MAVS
KW - MDA5
KW - Negative regulation
KW - RIG-I
UR - http://www.scopus.com/inward/record.url?scp=85017207278&partnerID=8YFLogxK
U2 - 10.1002/eji.201646484
DO - 10.1002/eji.201646484
M3 - Article
C2 - 28295214
AN - SCOPUS:85017207278
SN - 0014-2980
VL - 47
SP - 615
EP - 628
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 4
ER -