title: Regulation of RLR-mediated innate immune signaling--it is all about keeping the balance.
abstract: The current view of cytoplasmic RNA-mediated innate immune signaling involves the differential activation of the RNA helicases retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology-2 (LGP2) by distinct RNA viruses. RIG-I, MDA5 and LGP2 form the RIG-I like receptor family (RLR). Since the initial characterization of the RLRs rapid progress has been made in the understanding of the molecular mechanisms that upon virus infection lead to the activation of downstream signaling cascades and the subsequent induction of type I interferon (IFN) and proinflammatory cytokines by these receptors. However, antiviral responses must be tightly regulated in order to prevent uncontrolled production of type I IFN that might have deleterious effects on the host. Exploring the structural and molecular mechanisms that underlie RLR signaling thus was accompanied by the discovery of how RLR-dependent antiviral responses are modulated. This article summarizes the current understanding of endogenous regulation in RLR signaling by various intrinsic molecules that exert their regulatory function in both the steady state or upon viral infection by targeting multiple steps of the signaling cascade.
authors.affiliation: II. Medical Department, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Eisenächer
authors.forename: Anne
authors.initials: A
authors.lastname: Krug
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020365:RNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D054875:Ubiquitination / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D014779:Virus Replication / Q000502:physiology; D014780:Viruses / Q000276:immunology / Q000378:metabolism*; D000097905:Roundabout Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053487:DEAD-box RNA Helicases; D007370:Interferon Type I; D000072640:Interferon-Induced Helicase, IFIH1; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020365:RNA Helicases; D011956:Receptors, Cell Surface; C512612:MAVS protein, mouse; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins; C547666:Dhx58 protein, mouse; C452815:IFIH1 protein, human