Interferon-induced helicase C domain-containing protein 1

Definition:

Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and pro-inflammatory cytokines. Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV), mengo encephalomyocarditis virus (ENMG), and rhinovirus. Detects coronavirus SARS-CoV-2. Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines.

References:

[1]. Xin Yin, et al. MDA5 Governs the Innate Immune Response to SARS-CoV-2 in Lung Epithelial Cells. Cell Rep. 2021 Jan 12;34(2):108628. [Content Brief]

[2]. Ian T Lamborn, et al. Recurrent rhinovirus infections in a child with inherited MDA5 deficiency. J Exp Med. 2017 Jul 3;214(7):1949-1972. [Content Brief]

[3]. Andreas Pichlmair, et al. Activation of MDA5 requires higher-order RNA structures generated during virus infection. J Virol. 2009 Oct;83(20):10761-9. [Content Brief]

[4]. Chunyuan Zhao, et al. The E3 Ubiquitin Ligase TRIM40 Attenuates Antiviral Immune Responses by Targeting MDA5 and RIG-I. Cell Rep. 2017 Nov 7;21(6):1613-1623. [Content Brief]

[5]. Xiao Man Wu, et al. NOD1 Promotes Antiviral Signaling by Binding Viral RNA and Regulating the Interaction of MDA5 and MAVS. J Immunol. 2020 Apr 15;204(8):2216-2231. [Content Brief]

[6]. Alys Peisley, et al. Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21010-5. [Content Brief]

[7]. Darja Bamming, et al. Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2. J Biol Chem. 2009 Apr 10;284(15):9700-12. [Content Brief]

[8]. Antoine Rebendenne, et al. SARS-CoV-2 triggers an MDA-5-dependent interferon response which is unable to control replication in lung epithelial cells. J Virol. 2021 Jan 29;95(8):e02415-20. [Content Brief]

[9]. GuanQun Liu, et al. ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol. 2021 Apr;6(4):467-478. [Content Brief]

[10]. Roland Züst, et al. Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat Immunol. 2011 Feb;12(2):137-43. [Content Brief]

[11]. Miao Jiang, et al. Innate immune responses in human monocyte-derived dendritic cells are highly dependent on the size and the 5' phosphorylation of RNA molecules. J Immunol. 2011 Aug 15;187(4):1713-21. [Content Brief]

[12]. C Cocude, et al. A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication. J Gen Virol. 2003 Dec;84(Pt 12):3215-3225. [Content Brief]

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