title: [IFN-alpha-induced gp96 upregulation negatively affects the anti-HBV efficiency of IFN-alpha].
abstract: OBJECTIVE
  To investigate the effect of the Interferon-alpha-induced gp96 upregulation on the anti-HBV efficiency of Interferon-alpha (IFN-alpha).
  
  
  METHODS
  The effect of IFN-alpha on the transcription and expression of heat shock protein gp96 was determined by real-time PCR, luciferase reporter assay and Western blot. The effect of over-expression or knock-down of gp96 by transfection or RNA interference, and treatment with IFN-alpha on HBV expression and replication was examined by ELISA and RT-PCR.
  
  
  RESULTS
  IFN-alpha treatment led to increased gp96 expression in a time- and dose-dependent manner. The overexpression of gp96 enhanced HBV expression and replication, whereas downregulation of gp96 resulted in decreased HBV replication. Finally, we verified that blocking IFN-alpha-induced upregulation of gp96 significantly enhanced IFN-alpha-mediated HBV inhibitory effects.
  
  
  CONCLUSIONS
  IFN-alpha-induced upregulation of gp96 may negatively affect the anti-HBV function of IFN-alpha. These data provide valuable insight for enhancing the antiviral efficacy of IFN-alpha by simultaneous inhibition of gp96.
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. gaoyanzhou10@mails.ucas.ac.cn
authors.forename: Yanzhou
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Fan
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Lipeng
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Songdong
authors.initials: S
authors.lastname: Meng
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006509:Hepatitis B / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; C053387:endoplasmin