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p-STAT1 regulates the influenza A virus replication and inflammatory response in vitro and vivo

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  • p-STAT1 regulates the influenza A virus replication and inflammatory response in vitro and vivo

    Virology. 2019 Aug 25;537:110-120. doi: 10.1016/j.virol.2019.08.023. [Epub ahead of print]
    p-STAT1 regulates the influenza A virus replication and inflammatory response in vitro and vivo.

    Zhang S1, Huo C1, Xiao J2, Fan T1, Zou S3, Qi P2, Sun L4, Wang M5, Hu Y6.
    Author information

    1 Key Laboratory of Animal Epidemiology of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. 2 Key Laboratory of Veterinary Bioproduction and Chemical Medicine of the Ministry of Agriculture, Zhongmu Institutes of China Animal Husbandry Industry Co., Ltd, No. 156 Beiqing Road, Haidian District, Beijing, 100095, China. 3 National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, PR China. 4 Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, 410078, China. 5 Key Laboratory of Animal Epidemiology of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China; Key Laboratory of Veterinary Bioproduction and Chemical Medicine of the Ministry of Agriculture, Zhongmu Institutes of China Animal Husbandry Industry Co., Ltd, No. 156 Beiqing Road, Haidian District, Beijing, 100095, China. 6 Key Laboratory of Animal Epidemiology of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. Electronic address: 07033@cau.edu.cn.

    Abstract

    Influenza A virus infection activates various intracellular signaling pathways, which is mediated by the transcription factors. Here, a quantitative phosphoproteomic analysis of A549 cells after infection with influenza A virus (H5N1) was performed and we found that the transcription factor STAT1 was highly activated. Unexpectedly, upon inhibition of p-STAT1, titers of progeny virus and viral protein synthesis were both reduced. The STAT1 inhibitor Fludarabine (FLUD) inhibited an early progeny step in viral infection and reduced the levels of influenza virus genomic RNA (vRNA). Concomitantly, there was reduced expression of inflammatory cytokines in p-STAT1 inhibited cells. In vivo, suppression of p-STAT1 improved the survival of H5N1 virus-infected mice, reduced the pulmonary inflammatory response and viral burden. Thus, our data demonstrated a critical role for p-STAT1 in influenza virus replication and inflammatory responses. We speculate that STAT1 is an example of a putative antiviral signaling component to support effective replication.
    Copyright 2019 Elsevier Inc. All rights reserved.


    KEYWORDS:

    Fludarabine; Inflammation; Influenza a virus; STAT1; Virus genomic RNA

    PMID: 31493649 DOI: 10.1016/j.virol.2019.08.023
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