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[IFN-alpha-induced gp96 upregulation negatively affects the anti-HBV efficiency of IFN-alpha]
Yanzhou Gao1, Hongxia Fan2, Lipeng Qiu3
1Chinese 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
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.
Conclusion:
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.
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