首页|3Cpro of FMDV inhibits type Ⅱ interferon-stimulated JAK-STAT signaling pathway by blocking STAT1 nuclear translocation

3Cpro of FMDV inhibits type Ⅱ interferon-stimulated JAK-STAT signaling pathway by blocking STAT1 nuclear translocation

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Foot-and-mouth disease virus(FMDV)has developed various strategies to antagonize the host innate immunity.FMDV Lpro and 3Cpro interfere with type Ⅰ IFNs through different mechanisms.The structural protein VP3 of FMDV degrades Janus kinase 1 to suppress IFN-γ signaling transduction.Whether non-structural proteins of FMDV are involved in restraining type Ⅱ IFN signaling pathways is unknown.In this study,it was shown that FMDV replication was resistant to IFN-γ treatment after the infection was established and FMDV inhibited type Ⅱ IFN induced expression of IFN-γ-stimulated genes(ISGs).We also showed for the first time that FMDV non-structural protein 3C antagonized IFN-γ-stimulated JAK-STAT signaling pathway by blocking STAT1 nuclear translocation.3Cpro expression significantly reduced the ISGs transcript levels and palindromic gamma-activated sequences(GAS)promoter activity,without affecting the protein level,tyrosine phosphorylation,and homodimerization of STAT1.Finally,we provided evidence that 3C protease activity played an essential role in degrading KPNA1 and thus inhibited ISGs mRNA and GAS promoter activities.Our results reveal a novel mechanism by which an FMDV non-structural protein antagonizes host type Ⅱ IFN signaling.

Foot-and-mouth disease virus(FMDV)3CIFN-γJAK-STAT signaling pathwaySTAT1KPNA1

Xiangju Wu、Lei Chen、Chao Sui、Yue Hu、Dandan Jiang、Fan Yang、Laura C.Miller、Juntong Li、Xiaoyan Cong、Nataliia Hrabchenko、Changhee Lee、Yijun Du、Jing Qi

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Shandong Key Laboratory of Animal Disease Control and Breeding/Key Laboratory of Livestock and Poultry Multi-omics of MARA,Institute of Animal Science and Veterinary Medicine,Institute of Crop Germplasm Resources,Shandong Academy of Agricultural Sciences,Jinan,250100,China

College of Life Science,Shandong Normal University,Jinan,250358,China

State Key Laboratory of Veterinary Etiological Biology/National Foot and Mouth Disease Reference Laboratory/Key Laboratory of Animal Virology of Ministry of Agriculture,Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Lanzhou,730050,China

Department of Diagnostic Medicine and Pathobiology,College of Veterinary Medicine,Kansas State University,Manhattan,KS,66506,USA

College of Veterinary Medicine and Virus Vaccine Research Center,Gyeongsang National University,Jinju,52828,Republic of Korea

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National Key Research and Development Program of ChinaNatural Science Foundation of Shandong ProvinceNatural Science Foundation of Shandong ProvinceNatural Science Foundation of Shandong ProvinceNatural Science Foundation of Shandong ProvinceNational Natural Science Foundation of ChinaAgricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural SciencesAgricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural SciencesAgricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural Sciences

2021YFD1800300ZR2021ZD08ZR2020KC005ZR2021MC139ZR2020QC19632102710CXGC2023A21CXGC2021B03CXGC2022A17

2023

10.1016/j.virs.2023.03.003

中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD
影响因子：0.393
ISSN：1674-0769
年,卷(期)：2023.38(3)
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