About: MDA5 is a research topic. Over the lifetime, 740 publications have been published within this topic receiving 80681 citations. The topic is also known as: DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide & MDA-5.
TL;DR: This study suggests that extracellular and intracellular dsRNA signaling pathways may utilize different NF-kB members, and particularly the differential utilization of RELB may be a key mechanism for powerful inductions ofNF-kB regulated genes in the intrace cellular ds RNA signaling pathway.
Abstract: Background
Pattern recognition receptors (PRRs) for double-stranded RNA (dsRNA) are components of innate immunity that recognize the presence of viral infection and initiate efficient defense mechanisms. In addition to previously well-characterized signaling pathways that are mediated by PKR and TLR3, new intracellular dsRNA sensors, that are members of CARD and DExD/H box helicase family, have been identified. However, the molecular mechanisms involved in the signaling pathways mediated by these new dsRNA sensors have not been extensively characterized.
TL;DR: The authors show that the autoimmune disease-associated variant of human MDA5 is permanently switched on, and this mutation is associated with fatal autoimmune disease.
TL;DR: A novel mechanism by which MDA5 mediated CIV infection was revealed and provided new avenues for the development of antiviral strategies.
Abstract: MDA5 belongs to the RIG-I-like receptor family, which is involved in innate immunity. During viral infection, MDA5 generates an antiviral response by recognizing the ligand to activate interferon. However, the role and mechanism of MDA5 in canine influenza virus (CIV) infection are unclear. To understand the mechanism of canine MDA5-mediated innate immunity during CIV infection, we detected the distribution of MDA5 in beagles, and the structural prediction showed that MDA5 was mainly composed of a CARD domain, RD domain, and DExD/H helix structure. Moreover, we found that MDA5 inhibits CIV replication. Furthermore, in the dual luciferase assay, we revealed that the CARD region of MDA5 strongly activated the IFN-β promoter and mainly transmitted signals through the CARD region. Overexpression of the CARD region of MDA5 revealed that the MDA5-mediated signaling pathway could transmit signals by activating the IRF3/NF-κB and IRF3 promoters, promoting the expression of antiviral proteins and cytokine release, thereby inhibiting CIV replication. Upon silencing of MDA5, cytokine production decreased, while the replication ability of CIV was increased. Thus, this study revealed a novel mechanism by which MDA5 mediated CIV infection and provided new avenues for the development of antiviral strategies.
TL;DR: The results indicated that the promoter and the Piggybac-MDA5-DsRed cell line could be utilized to determine whether a ligand regulates MDA5 expression, and provides a tool for testing chMda5 expression and regulation.
TL;DR: RIG-I and MDA5 may be involved in inflammatory reactions by regulating CXCL10 expression in the downstream of TLR4 signaling in human mesangial cells.
Abstract: EPHROL AbstrAct Background: It is known that recognition of bacterial lipopolysaccharide (LPS) and various endogenous li- gands by Toll-like receptor 4 (TLR4) induces inflam- matory reactions. However, the role of TLR4 activation in mesangial inflammation remains to be elucidated. Retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are putative RNA helicases and are involved in immune and inflam- matory reactions. The purpose of the present study was to investigate the implication of RIG-I and MDA5