IFN-α对gp96的上调降低其抗HBV的效率

IFN-α-induced gp96 upregulation negatively affects the anti-HBV efficiency of IFN-α

【目的】探讨IFN-α上调热休克蛋白gp96对其抗HBV作用的影响。【方法】首先通过RT-PCR、荧光报告基因和Western blot在转录和蛋白水平上研究IFN-α对gp96上调的时间、剂量依赖性。其次,利用RT-PCR、ELISA分别研究转染表达gp96、RNA干扰gp96对HBV复制的影响。最后,通过ELISA、RT-PCR研究RNA干扰gp96后IFN-α抗HBV的作用。【结果】发现IFN-α对gp96的上调具有时间、剂量依赖性。而gp96的上调促进了HBV的复制,消除IFN-α对gp96的上调显著增强IFN-α抗HBV的效率。【结论】IFN-α上调gp96对其抗乙肝病毒功能起负面影响,抑制gp96上调可增强IFN-α的抗病毒效果。

[ Objective] To investigate the effect of the Interferon-a-induced gp96 upregulation on the anti-HBV efficiency of Interferon-α（IFN-α）. [Methods] The effect of IFN-α 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 transfeetion or RNA interference, and treatment with IFN-α on HBV expression and replication was examined by ELISA and RT-PCR. [ Results ] IFN-α 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-α-induced upregulation of gp96 significantly enhanced IFN-α-mediated HBV inhibitory effects. [ Conclusion ] IFN-α-induced upregulation of gp96 may negatively affect the anti-HBV function of IFN-α. These data provide valuable insight for enhancing the antiviral efficacy of IFN-α by simultaneous inhibition of gp96.