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乙型肝炎病毒抑制α-干扰素诱导抗病毒蛋白表达的研究 预览 被引量:1

Study of the effect of hepatitis B virus on interferon-induced antiviral proteins expression
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摘要 目的探讨乙型肝炎病毒(HBV)对α-干扰素(IFN-α)诱导抗病毒蛋白表达的影响及其机制。方法以人肝胚瘤细胞株HepG2为研究对象,将能够表达完整HBV病毒颗粒的质粒pSM2转染HepG2细胞,再将0~1 000 IU/ml浓度IFN-α处理细胞6 h,运用ELISA和Southern blot技术分析转染细胞上清HBV抗原和细胞内HBV DNA以判断HBV复制情况;以Northern blot技术分析转染前后HepG2细胞的IFN-α应答情况,检测抗病毒蛋白(如MxA、2',5'-OAS等),并进一步分析IFN-αJAK-STAT信号转导途径分子STAT1的表达。结果转染HBV全基因组序列表达质粒pSM2的HepG2细胞能够表达完整的HBV颗粒,且随着转染时间的延长,HBV颗粒或抗原表达量逐步增加。Northern blot分析提示HepG2细胞能够表达IFN-α抗病毒蛋白:MxA、2',5'-OAS,但转染pSM2质粒的HepG2细胞,IFN-α抗病毒蛋白MxA、2',5'-OAS表达量明显减低;同时重要的IFN-αJAK-STAT信号转导途径分子STAT1表达也随着HBV颗粒的表达而受到抑制。结论 HBV可能通过下调IFN-αJAK-STAT信号转导途径分子STAT1的表达,从而抑制抗病毒蛋白如MxA、2',5'-OAS的表达,这很可能是HBV拮抗IFN-α抗病毒活性的重要机制之一。 Objective To investigate the effect of HBV on the interferon-alpha(INF-α) induced antiviral proteins expression and its mechanisms.Methods The HepG2 cells were transfected with pSM2,which contained full-length HBV sequence dimmer and could express HBV whole particles.And then,the cells were treated with 0~1 000 IU/ml of IFN-α for 6 h.Further,Southern blot was applied to analyse intracellular HBV replicative intermediate DNA,while ELISA assay was used for analysing the secreted HBV antigens.Meanwhile,Northern blot was performed to analyse the expresssion of the antiviral proteins,such as MxA,2′,5′-OAS,as well as the JAK-STAT signal transduction pathway molecules,STAT1 in HepG2 cells.Results The HepG2 cells who transfected with pSM2 plasmid could express whole HBV particles,and with the course of transfection time,the expressed HBV particles and antigens amounts increased significantly.Further,Northern blot analysis indicated that the HepG2 cells could express IFN-α antiviral proteins,such as MxA and 2',5'-OAS.When transfected with pSM2 plasmids,the IFN-α antiviral proteins MxA and 2′,5′-OAS in transfected cells were reduced greatly compared with the un-transfected HepG2 cell.Furthermore,in this reserach,the important IFN-α JAK-STAT signal transduction pathway molecules,the STAT1,was also found inhibited expression with the expression of HBV particles in transfected HepG2 cells.Conclusion HBV could inhibit the expression of antiviral protein,which involve in the induction of STAT1.It is probably that HBV has the mechanism to antagonise the IFN-α antiviral activity.
作者 管世鹤 杨凯 潘颖 Guan Shihe,Yang Kai,Pan Ying(Dept of Clinical Laboratory,The Second Affiliated Hospital of Anhui Medical University,Hefei 230601)
出处 《安徽医科大学学报》 CAS 北大核心 2011年第4期 324-327,共4页 Acta Universitis Medicinalis Anhui
基金 国家自然科学基金(编号:30600522) 安徽省卫生厅科学基金(编号:2010C057)
关键词 肝炎病毒 乙型 干扰素Α STAT1转录因子 hepatitis B virus interferon-alpha STAT1 transcription factor
作者简介 管世鹤,男,副教授,副主任技师,硕士生导师,责任作者,E—mail:shiheguan@126.com
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