title: Suppression of USP18 Potentiates the Anti-HBV Activity of Interferon Alpha in HepG2.2.15 Cells via JAK/STAT Signaling.
abstract: Ubiquitin-specific protease 18 (USP18, also known as UBP43) has both interferon stimulated gene 15 (ISG15) dependent and ISG15-independent functions. By silencing the expression of USP18 in HepG2.2.15 cells, we studied the effect of USP18 on the anti-HBV activity of IFN-F and demonstrated that knockdown of USP18 significantly Inhibited the HBV expression and increased the expression of ISGs. Levels of hepatitis B virus surface antigen (HBsAg), hepatitis B virus e antigen (HBeAg), HBV DNA and intracellular hepatitis B virus core antigen (HBcAg) were dramatically decreased with or without treatment of indicated dose of IFN-F. Suppression of USP18 activated the JAK/STAT signaling pathway as shown by the increased and prolonged expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT1) in combination with enhanced expression of several interferon stimulated genes (ISGs). Our results indicated that USP18 modulates the anti-HBV activity of IFN-F via activation of the JAK/STAT signaling pathway in Hepg2.2.15 cells.
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China.
authors.forename: Qing-Song
authors.initials: QS
authors.lastname: Lei
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China.
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China.|The Nursing College of Chongqing Medical University, Chongqing, 400016, P.R. China.
authors.forename: Ling-Na
authors.initials: LN
authors.lastname: Kong
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
mesh_terms: D004279:DNA, Viral / Q000276:immunology; D010450:Endopeptidases / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000276:immunology; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D053612:Janus Kinases / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D043222:Ubiquitin Thiolesterase
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D053612:Janus Kinases; D010450:Endopeptidases; C485560:USP18 protein, human; D043222:Ubiquitin Thiolesterase