title: FAT10 Is Critical in Influenza A Virus Replication by Inhibiting Type I IFN.
abstract: The H5N1 avian influenza virus causes severe disease and high mortality, making it a major public health concern worldwide. The virus uses the host cellular machinery for several steps of its life cycle. In this report, we observed overexpression of the ubiquitin-like protein FAT10 following live H5N1 virus infection in BALB/c mice and in the human respiratory epithelial cell lines A549 and BEAS-2B. Further experiments demonstrated that FAT10 increased H5N1 virus replication and decreased the viability of infected cells. Total RNA extracted from H5N1 virus-infected cells, but not other H5N1 viral components, upregulated FAT10, and this process was mediated by the retinoic acid-induced protein I-NF-κB signaling pathway. FAT10 knockdown in A549 cells upregulated type I IFN mRNA expression and enhanced STAT1 phosphorylation during live H5N1 virus infection. Taken together, our data suggest that FAT10 was upregulated via retinoic acid-induced protein I and NF-κB during H5N1 avian influenza virus infection. And the upregulated FAT10 promoted H5N1 viral replication by inhibiting type I IFN.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Yanli
authors.identifier: 0000-0003-1481-6361
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Qiang
authors.identifier: 0000-0002-6343-8080
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Qingchao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Yanxu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Ning
authors.identifier: 0000-0002-1626-5519
authors.initials: N
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Shunwang
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Huandi
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130062, China;
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130062, China;
authors.forename: Mingyao
authors.initials: M
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Jiejie
authors.identifier: 0000-0001-5612-844X
authors.initials: J
authors.lastname: Deng
authors.affiliation: Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology, Tsinghua University, Beijing 100084, China;
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China;
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130062, China;
authors.forename: Huijun
authors.initials: H
authors.lastname: Lu
authors.affiliation: Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology, Tsinghua University, Beijing 100084, China; Department of Molecular and Cell Biology, Center for Systems Biology, University of Texas at Dallas, Richardson, TX 75080; and.
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130062, China; jiang@pumc.edu.cn ningyik@126.com.
authors.forename: Ningyi
authors.initials: N
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China; State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610000, China jiang@pumc.edu.cn ningyik@126.com.
authors.forename: Chengyu
authors.identifier: 0000-0003-0570-2709
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D055785:Gene Knockdown Techniques; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D007370:Interferon Type I / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014452:Ubiquitins / Q000378:metabolism*; D015854:Up-Regulation; D014779:Virus Replication / Q000502:physiology*
chemical_list: C512253:FAT10 protein, mouse; D007370:Interferon Type I; C109184:UBD protein, human; D014452:Ubiquitins