CSFV Npro protein can suppress innate antiviral responses induced by poly(I:C) and influenza A virus
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  • SHI Wenhao

    SHI Wenhao

    Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Fujian-Nepal Joint Laboratory of Animal Pathogen Prevention and Control, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China
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  • CAI Binxiang

    CAI Binxiang

    Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Fujian-Nepal Joint Laboratory of Animal Pathogen Prevention and Control, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China
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  • YANG Bincai

    YANG Bincai

    Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Fujian-Nepal Joint Laboratory of Animal Pathogen Prevention and Control, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China
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  • QIU Haori

    QIU Haori

    Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Fujian-Nepal Joint Laboratory of Animal Pathogen Prevention and Control, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China
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  • WEN Faxin

    WEN Faxin

    Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Fujian-Nepal Joint Laboratory of Animal Pathogen Prevention and Control, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China
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  • CHI Xiaojuan

    CHI Xiaojuan

    Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Fujian-Nepal Joint Laboratory of Animal Pathogen Prevention and Control, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China
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  • WANG Song

    WANG Song

    Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Fujian-Nepal Joint Laboratory of Animal Pathogen Prevention and Control, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China
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  • CHEN Yuhai

    CHEN Yuhai

    CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
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  • LIAO Yuan

    LIAO Yuan

    Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Fujian-Nepal Joint Laboratory of Animal Pathogen Prevention and Control, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China
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  • CHEN Ye

    CHEN Ye

    Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Fujian-Nepal Joint Laboratory of Animal Pathogen Prevention and Control, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China
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  • CHEN Ji-Long

    CHEN Ji-Long

    Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Fujian-Nepal Joint Laboratory of Animal Pathogen Prevention and Control, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
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  • MA Shujie

    MA Shujie

    Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Fujian-Nepal Joint Laboratory of Animal Pathogen Prevention and Control, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China;Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China
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    Abstract:

    [Objective] Classical swine fever virus (CSFV) causes a highly contagious porcine disease that is characterized by hemorrhage syndrome and immunosuppression. In this paper, we studied the mechanism of CSFV inhibiting the host's innate immunity and its potential effect on influenza A virus (IAV) infection under immunosuppressive conditions. [Methods] First, the expression of interferons (IFNs) and IFN-stimulated genes (ISGs) and the phosphorylation of signal transducer and activator of transcription 1 (STAT1) induced by poly(I:C) in PK-15 cells which had been infected by CSFV were detected by reverse transcription-PCR (RT-PCR), reverse transcription-quantitative PCR (RT-qPCR), and Western blotting to explore the effect of CSFV on host innate immunity. Then, cells overexpressing CSFV proteins were used to screen and identify the key protein inhibiting the innate immunity. Finally, the potential influence of CSFV Npro on innate immunity and IAV infection was examined in Npro-overexpressing PK-15 cells by RT-PCR, RT-qPCR, Western blotting, and plaque assay. [Results] CSFV suppressed expression of type Ⅰ and type Ⅲ IFNs induced by poly(I:C). CSFV Npro protein directly inhibited STAT1 phosphorylation and caused down-regulation of oligoadenylate synthase-like (OASL) protein, 2'-5'-oligoadenylate synthase-1 (OAS1), IFN-induced transmembrane protein 3 (IFITM3), and interferon-stimulated gene 15 (ISG15) in vitro. Moreover, CSFV Npro protein suppressed the expression of type Ⅰ and type Ⅲ IFNs induced by IAV, and caused a dramatic decline in phosphorylation of STAT1 and expression of OASL, OAS1, IFITM3, and ISG15, thereby significantly promoting the replication of IAV in the Npro-overexpressing PK-15 cells. [Conclusion] CSFV Npro protein antagonizes the innate antiviral response induced by poly(I:C) and IAV, suggesting that Npro protein can inhibit the RIG-I-dependent signaling pathway and promote IAV replication in the Npro-expressing PK-15 cells.

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SHI Wenhao, CAI Binxiang, YANG Bincai, QIU Haori, WEN Faxin, CHI Xiaojuan, WANG Song, CHEN Yuhai, LIAO Yuan, CHEN Ye, CHEN Ji-Long, MA Shujie. CSFV Npro protein can suppress innate antiviral responses induced by poly(I:C) and influenza A virus. [J]. Acta Microbiologica Sinica, 2022, 62(12): 4894-4917

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History
  • Received:March 29,2022
  • Revised:April 29,2022
  • Online: December 08,2022
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