Pyruvate Carboxylase Activates the RIG-I-like Receptor-Mediated Antiviral Immune Response by Targeting the MAVS signalosome

Scientific Reports
Zhongying CaoYing Zhu

Abstract

When retinoic acid-inducible gene 1 protein (RIG-I)-like receptors sense viral dsRNA in the cytosol, RIG-I and melanoma differentiation-associated gene 5 (MDA5) are recruited to the mitochondria to interact with mitochondrial antiviral signaling protein (MAVS) and initiate antiviral immune responses. In this study, we demonstrate that the biotin-containing enzyme pyruvate carboxylase (PC) plays an essential role in the virus-triggered activation of nuclear factor kappa B (NF-κB) signaling mediated by MAVS. PC contributes to the enhanced production of type I interferons (IFNs) and pro-inflammatory cytokines, and PC knockdown inhibits the virus-triggered innate immune response. In addition, PC shows extensive antiviral activity against RNA viruses, including influenza A virus (IAV), human enterovirus 71 (EV71), and vesicular stomatitis virus (VSV). Furthermore, PC mediates antiviral action by targeting the MAVS signalosome and induces IFNs and pro-inflammatory cytokines by promoting phosphorylation of NF-κB inhibitor-α (IκBα) and the IκB kinase (IKK) complex, as well as NF-κB nuclear translocation, which leads to activation of interferon-stimulated genes (ISGs), including double-stranded RNA-dependent protein kinase (PKR) and myx...Continue Reading

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Citations

Oct 21, 2016·Drug Development Research·Walter H MoosKosta Steliou
Jan 25, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Udom Lao-OnSarawut Jitrapakdee
Mar 31, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhangchuan XiaYing Zhu
May 2, 2017·Immune Network·Hyo Sun JinEun-Kyeong Jo
Sep 22, 2021·Molecular Cell·Sebastian IgelmannGerardo Ferbeyre

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Methods Mentioned

BETA
ubiquitination
transfection
co-immunoprecipitation
confocal microscopy
PCR
confocal laser

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