title: Interferon-Stimulated Gene 15 Conjugation Stimulates Hepatitis B Virus Production Independent of Type I Interferon Signaling PathwayIn Vitro.
abstract: Hepatitis B virus (HBV) is an important account of infectious hepatitis and interferon (IFN) remains one of the best treatment options. Activation of type I IFN signaling pathway leads to expressions of IFN-stimulated genes (ISGs) which play important roles in antiviral and immunomodulatory responses to HBV or hepatitis C virus (HCV) infection. Our previous studies indicated that ISG15 and its conjugation (ISGylation) were exploited by HCV to benefit its replication and persistent infection. This study was designed to assess the role of ISG15 and ISGylation in HBV infectionin vitro. The levels of ISG15 and ISGylation were upregulated by ISG15 plasmid transfection into HepG2.2.15 cells. Decreased ISGylation was achieved by siRNA targeting UBE1L, the only E1 activating enzyme for ISGylation. Overexpression of ISG15 and subsequent ISGylation significantly increased the levels of HBV DNA in the culture supernatants although the intracellular viral replication remained unaffected. Silencing UBE1L, with decreased ISGylation achieved, abrogated this ISGylation-mediated promoting effect. Our data indicated that overexpression of ISG15 stimulated HBV production in an ISGylation-dependent manner. Identification of ISG15-conjugated proteins (either HBV viral or host proteins) may reveal promising candidates for further antiviral drug development.
authors.affiliation: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory for Transfusion-Transmitted Diseases of Sichuan Province, Chengdu, Sichuan 610052, China.
authors.forename: Yujia
authors.identifier: 0000-0002-2636-5468
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory for Transfusion-Transmitted Diseases of Sichuan Province, Chengdu, Sichuan 610052, China.
authors.forename: Shilin
authors.identifier: 0000-0001-7065-6150
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory for Transfusion-Transmitted Diseases of Sichuan Province, Chengdu, Sichuan 610052, China.
authors.forename: Xiaoqiong
authors.identifier: 0000-0002-3556-6739
authors.initials: X
authors.lastname: Duan
authors.affiliation: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory for Transfusion-Transmitted Diseases of Sichuan Province, Chengdu, Sichuan 610052, China.
authors.forename: Yanzhao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory for Transfusion-Transmitted Diseases of Sichuan Province, Chengdu, Sichuan 610052, China.
authors.forename: Baihai
authors.initials: B
authors.lastname: Jiao
authors.affiliation: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory for Transfusion-Transmitted Diseases of Sichuan Province, Chengdu, Sichuan 610052, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ye
authors.affiliation: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory for Transfusion-Transmitted Diseases of Sichuan Province, Chengdu, Sichuan 610052, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.affiliation: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory for Transfusion-Transmitted Diseases of Sichuan Province, Chengdu, Sichuan 610052, China; Toronto General Research Institute, University of Toronto, Toronto, ON, Canada M5G 1L6.
authors.forename: Limin
authors.identifier: 0000-0002-7370-6499
authors.initials: L
authors.lastname: Chen
mesh_terms: D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D016898:Interferon-alpha; D014452:Ubiquitins; C074034:ISG15 protein, human; C534879:UBA7 protein, human; D044764:Ubiquitin-Activating Enzymes