title: Antibody-dependent enhancement of dengue virus infection inhibits RLR-mediated Type-I IFN-independent signalling through upregulation of cellular autophagy.
abstract: Antibody dependent enhancement (ADE) of dengue virus (DENV) infection is identified as the main risk factor of severe Dengue diseases. Through opsonization by subneutralizing or non-neutralizing antibodies, DENV infection suppresses innate cell immunity to facilitate viral replication. However, it is largely unknown whether suppression of type-I IFN is necessary for a successful ADE infection. Here, we report that both DENV and DENV-ADE infection induce an early ISG (NOS2) expression through RLR-MAVS signalling axis independent of the IFNs signaling. Besides, DENV-ADE suppress this early antiviral response through increased autophagy formation rather than induction of IL-10 secretion. The early induced autophagic proteins ATG5-ATG12 participate in suppression of MAVS mediated ISGs induction. Our findings suggest a mechanism for DENV to evade the early antiviral response before IFN signalling activation. Altogether, these results add knowledge about the complexity of ADE infection and contribute further to research on therapeutic strategies.
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming 650118, PR China.|Yunnan Key Laboratory of Vaccine Research &Development on Severe Infectious Diseases, Kunming 650118, PR China.|Key Laboratory of The Second Affiliated Hospital of Kuming Medical College, Kunming 650101, PR China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming 650118, PR China.|Yunnan Key Laboratory of Vaccine Research &Development on Severe Infectious Diseases, Kunming 650118, PR China.
authors.forename: Yaofei
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming 650118, PR China.|Yunnan Key Laboratory of Vaccine Research &Development on Severe Infectious Diseases, Kunming 650118, PR China.
authors.forename: Duo
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming 650118, PR China.|Yunnan Key Laboratory of Vaccine Research &Development on Severe Infectious Diseases, Kunming 650118, PR China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming 650118, PR China.|Yunnan Key Laboratory of Vaccine Research &Development on Severe Infectious Diseases, Kunming 650118, PR China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming 650118, PR China.|Yunnan Key Laboratory of Vaccine Research &Development on Severe Infectious Diseases, Kunming 650118, PR China.
authors.forename: Junying
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming 650118, PR China.|Yunnan Key Laboratory of Vaccine Research &Development on Severe Infectious Diseases, Kunming 650118, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming 650118, PR China.|Yunnan Key Laboratory of Vaccine Research &Development on Severe Infectious Diseases, Kunming 650118, PR China.
authors.forename: Juemin
authors.initials: J
authors.lastname: Xi
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming 650118, PR China.|Yunnan Key Laboratory of Vaccine Research &Development on Severe Infectious Diseases, Kunming 650118, PR China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming 650118, PR China.|Yunnan Key Laboratory of Vaccine Research &Development on Severe Infectious Diseases, Kunming 650118, PR China.
authors.forename: Qiangming
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming 650118, PR China.|Yunnan Key Laboratory of Vaccine Research &Development on Severe Infectious Diseases, Kunming 650118, PR China.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Li
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D001343:Autophagy; D002460:Cell Line; D000071457:DEAD Box Protein 58 / Q000378:metabolism; D003715:Dengue / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D003716:Dengue Virus / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000378:metabolism*; D000072640:Interferon-Induced Helicase, IFIH1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009570:Nitriles; D011759:Pyrrolidines; D012367:RNA, Viral / Q000096:biosynthesis; D011971:Receptors, Immunologic; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D015854:Up-Regulation; D019562:Viral Load; D014779:Virus Replication
chemical_list: C494668:(S)-1-(4-methyl-1-(2-pyrimidinyl)-4-piperidylamino)acetyl-2-pyrrolidinecarbonitrile; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007370:Interferon Type I; D009570:Nitriles; D011759:Pyrrolidines; D012367:RNA, Viral; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D000072640:Interferon-Induced Helicase, IFIH1