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      SOCS Proteins Participate in the Regulation of Innate Immune Response Caused by Viruses

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          Abstract

          The host immune system has multiple innate immune receptors that can identify, distinguish and react to viral infections. In innate immune response, the host recognizes pathogen-associated molecular patterns (PAMP) in nucleic acids or viral proteins through pathogen recognition receptors (PRRs), especially toll-like receptors (TLRs) and induces immune cells or infected cells to produce type I Interferons (IFN-I) and pro-inflammatory cytokines, thus when the virus invades the host, innate immunity is the earliest immune mechanism. Besides, cytokine-mediated cell communication is necessary for the proper regulation of immune responses. Therefore, the appropriate activation of innate immunity is necessary for the normal life activities of cells. The suppressor of the cytokine signaling proteins (SOCS) family is one of the main regulators of the innate immune response induced by microbial pathogens. They mainly participate in the negative feedback regulation of cytokine signal transduction through Janus kinase signal transducer and transcriptional activator (JAK/STAT) and other signal pathways. Taken together, this paper reviews the SOCS proteins structures and the function of each domain, as well as the latest knowledge of the role of SOCS proteins in innate immune caused by viral infections and the mechanisms by which SOCS proteins assist viruses to escape host innate immunity. Finally, we discuss potential values of these proteins in future targeted therapies.

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          Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors.

          Induction of type I interferons (IFNs) by viruses and other pathogens is crucial for innate immunity, and it is mediated by the activation of pattern-recognition receptors, such as Toll-like receptors and cytosolic receptors such as RIG-I and MDA5. The type I IFN induction is primarily controlled at the gene transcriptional level, wherein a family of transcription factors, interferon regulatory factors (IRFs), plays central roles. Here, we summarize the recent studies on IRFs, providing a paradigm of how genes are ingeniously regulated during immune responses. We also consider some evolutional aspects on the IFN-IRF system.
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            Innate immunity to virus infection.

            The innate immune system is essential for the initial detection of invading viruses and subsequent activation of adaptive immunity. Three classes of receptors, designated retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), Toll-like receptors (TLRs), and nucleotide oligomerization domain (NOD)-like receptors (NLRs), sense viral components, such as double-stranded RNA (dsRNA), single-stranded RNA, and DNA. RLRs and TLRs play essential roles in the production of type I interferons (IFNs) and proinflammatory cytokines in cell type-specific manners. While the RLRs play essential roles in the recognition of RNA viruses in various cells, plasmacytoid dendritic cells utilize TLRs for detecting virus invasion. NLRs play a role in the production of mature interleukin-1 beta to dsRNA stimulation. Activation of innate immune cells is critical for mounting adaptive immune responses. In this review, we discuss recent advances in our understanding of the mechanisms of viral RNA recognition by these different types of receptors and its relation to acquired immune responses.
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              SOCS proteins, cytokine signalling and immune regulation.

              Suppressor of cytokine signalling (SOCS) proteins are inhibitors of cytokine signalling pathways. Studies have shown that SOCS proteins are key physiological regulators of both innate and adaptive immunity. These molecules positively and negatively regulate macrophage and dendritic-cell activation and are essential for T-cell development and differentiation. Evidence is also emerging of the involvement of SOCS proteins in diseases of the immune system. In this Review we bring together data from recent studies on SOCS proteins and their role in immunity, and propose a cohesive model of how cytokine signalling regulates immune-cell function.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                25 September 2020
                2020
                : 11
                : 558341
                Affiliations
                [1] 1Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University , Chengdu, China
                [2] 2Institute of Preventive Veterinary Medicine, Sichuan Agricultural University , Chengdu, China
                [3] 3Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University , Chengdu, China
                Author notes

                Edited by: Hans A. R. Bluyssen, Adam Mickiewicz University, Poland

                Reviewed by: Chien-Kuo Lee, National Taiwan University, Taiwan; Jeffrey James Babon, Walter and Eliza Hall Institute of Medical Research, Australia

                *Correspondence: Renyong Jia jiary@ 123456sicau.edu.cn

                This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2020.558341
                7544739
                33072096
                e0a1a837-d91a-4f11-bdc3-85fe228dcf71
                Copyright © 2020 Huang, Liu, Cheng, Wang, Cui, Huang, Zhu, Chen, Liu, Zhao, Wu, Yang, Zhang, Ou, Mao, Gao, Yu, Tian, Liu, Zhang, Yin, Jing, Chen and Jia.

                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
                : 02 May 2020
                : 24 August 2020
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 201, Pages: 15, Words: 13399
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 31872475
                Award ID: 31902267
                Funded by: Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System 10.13039/501100012438
                Award ID: SCCXTD-2020-18
                Funded by: China Agricultural Research System 10.13039/501100012453
                Award ID: CARS-42-17
                Categories
                Immunology
                Review

                Immunology
                suppressor of cytokine signaling proteins,virus,innate immune,cytokine,tlr
                Immunology
                suppressor of cytokine signaling proteins, virus, innate immune, cytokine, tlr

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