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      Histone deacetylase 8 promotes innate antiviral immunity through deacetylation of RIG-I

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          Abstract

          Histone deacetylates family proteins have been studied for their function in regulating viral replication by deacetylating non-histone proteins. RIG-I (Retinoic acid-inducible gene I) is a critical protein in RNA virus-induced innate antiviral signaling pathways. Our previous research showed that HDAC8 (histone deacetylase 8) involved in innate antiviral immune response, but the underlying mechanism during virus infection is still unclear. In this study, we showed that HDAC8 was involved in the regulation of vesicular stomatitis virus (VSV) replication. Over-expression of HDAC8 inhibited while knockdown promoted VSV replication. Further exploration demonstrated that HDAC8 interacted with and deacetylated RIG-I, which eventually lead to enhance innate antiviral immune response. Collectively, our data clearly demonstrated that HDAC8 inhibited VSV replication by promoting RIG-I mediated interferon production and downstream signaling pathway.

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          Most cited references32

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          Functions and mechanisms of non-histone protein acetylation

          Takeo Narita, Brian T. Weinert, Chunaram Choudhary (2018)
          Nε-lysine acetylation was discovered more than half a century ago as a post-translational modification of histones and has been extensively studied in the context of transcription regulation. In the past decade, proteomic analyses have revealed that non-histone proteins are frequently acetylated and constitute a major portion of the acetylome in mammalian cells. Indeed, non-histone protein acetylation is involved in key cellular processes relevant to physiology and disease, such as gene transcription, DNA damage repair, cell division, signal transduction, protein folding, autophagy and metabolism. Acetylation affects protein functions through diverse mechanisms, including by regulating protein stability, enzymatic activity, subcellular localization and crosstalk with other post-translational modifications and by controlling protein-protein and protein-DNA interactions. In this Review, we discuss recent progress in our understanding of the scope, functional diversity and mechanisms of non-histone protein acetylation.
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            Immune signaling by RIG-I-like receptors.

            Yueh-Ming Loo, Michael Gale (2011)
            The RIG-I-like receptors (RLRs) RIG-I, MDA5, and LGP2 play a major role in pathogen sensing of RNA virus infection to initiate and modulate antiviral immunity. The RLRs detect viral RNA ligands or processed self RNA in the cytoplasm to trigger innate immunity and inflammation and to impart gene expression that serves to control infection. Importantly, RLRs cooperate in signaling crosstalk networks with Toll-like receptors and other factors to impart innate immunity and to modulate the adaptive immune response. RLR regulation occurs at a variety of levels ranging from autoregulation to ligand and cofactor interactions and posttranslational modifications. Abberant RLR signaling or dysregulation of RLR expression is now implicated in the development of autoimmune diseases. Understanding the processes of RLR signaling and response will provide insights to guide RLR-targeted therapeutics for antiviral and immune-modifying applications. Copyright © 2011 Elsevier Inc. All rights reserved.
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              RIG-I-like receptors: their regulation and roles in RNA sensing.

              Jan Rehwinkel, Michaela U. Gack (2020)
              Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are key sensors of virus infection, mediating the transcriptional induction of type I interferons and other genes that collectively establish an antiviral host response. Recent studies have revealed that both viral and host-derived RNAs can trigger RLR activation; this can lead to an effective antiviral response but also immunopathology if RLR activities are uncontrolled. In this Review, we discuss recent advances in our understanding of the types of RNA sensed by RLRs in the contexts of viral infection, malignancies and autoimmune diseases. We further describe how the activity of RLRs is controlled by host regulatory mechanisms, including RLR-interacting proteins, post-translational modifications and non-coding RNAs. Finally, we discuss key outstanding questions in the RLR field, including how our knowledge of RLR biology could be translated into new therapeutics.
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                Author and article information

                Contributors
                Huijun Zhang: URI : https://loop.frontiersin.org/people/2701270Role: Role: Role: Role: Role:
                Tingli Liu: URI : https://loop.frontiersin.org/people/577394Role: Role:
                Xinhua Liu: Role: Role:
                Fenfen You: Role: Role:
                Jiaheng Yang: Role: Role:
                Nan Zhang: Role: Role: Role:
                Ying Huang: URI : https://loop.frontiersin.org/people/2768618Role: Role:
                Gaofeng Liang: URI : https://loop.frontiersin.org/people/120045Role: Role: Role:
                Journal
                Journal ID (nlm-ta): Front Cell Infect Microbiol
                Journal ID (iso-abbrev): Front Cell Infect Microbiol
                Journal ID (publisher-id): Front. Cell. Infect. Microbiol.
                Title: Frontiers in Cellular and Infection Microbiology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2235-2988
                Publication date (Electronic): 05 July 2024
                Publication date Collection: 2024
                Volume: 14
                Electronic Location Identifier: 1415695
                Affiliations
                [1] 1 Institute of Biomedical Research, Henan Academy Of Sciences , Zhengzhou, China
                [2] 2 School of Basic Medical and Forensic Medicine, Henan University of Science & Technology , Luoyang, China
                [3] 3 Department of Medical Laboratory, Fenyang College of Shanxi Medical University , Fenyang, China
                [4] 4 Pharmacy Department, Luohe Hosptial Of Traditional Chinese Medicine , Luohe, China
                Author notes

                Edited by: Satish Devadas, Institute of Life Sciences (ILS), India

                Reviewed by: Xinyu Zhu, Duke University, United States

                Soumya SenGupta, National Cancer Institute at Frederick (NIH), United States

                Thiruvaimozhi Abimannan, National Cancer Institute at Frederick (NIH), United States

                *Correspondence: Huijun Zhang, zhanghuijun529@ 123456163.com ; Gaofeng Liang, lgfeng990448@ 123456163.com
                Article
                DOI: 10.3389/fcimb.2024.1415695
                PMC ID: 11257846
                PubMed ID: 39035358
                SO-VID: 8c1925c5-ca35-4c45-8895-ba4396653441
                Copyright © Copyright © 2024 Zhang, Liu, Liu, You, Yang, Zhang, Huang and Liang
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 11 April 2024
                Date accepted : 25 June 2024
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 32, Pages: 9, Words: 4156
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the Startup Research Fund of Henan Academy of Sciences (NO.241828052), Joint Fund of Henan Province Science and Technology R&D Program (NO.225200810080), the Key R&D project of Henan Province (221111310600), Special Foundation for Basic Research Program of Higher Education Institutions of Henan Province (22ZX005), and Joint Fund of Henan Province Science and Technology R&D Program (225200810020).
                Categories
                Subject: Cellular and Infection Microbiology
                Subject: Original Research
                Custom metadata
                section-in-acceptance Microbes and Innate Immunity

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: hdac8,antiviral,vsv,innate immunity,molecular mechanism
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: hdac8, antiviral, vsv, innate immunity, molecular mechanism

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