乙型肝炎病毒与Ⅰ型干扰素系统相互作用新机制及治疗新策略的研究

Interplay between hepatitis B virus and the typeⅠinterferon system and new therapeutic strategies

乙型肝炎病毒(Hepatitis B virus,HBV)感染是严重危害人类健康的重要疾病之一,迄今尚无治愈药物。干扰素(interferon,IFN)由于HBeAg/HBsAg血清转换清除率较高、获得疗效后复发率低,成为临床抗乙肝病毒药物之一,但由于仅约20%~40%的患者对IFN有较好应答,其临床应用受到很大阻碍。鉴于此,国内外学者近年来利用体外HBV复制感染细胞模型及动物模型与临床乙型肝炎患者队列,采用多种研究手段,一方面研究IFN及IFN诱导的细胞基因在抗HBV及信号传导途径中的作用及新机制,另一方面研究HBV复制和蛋白表达对天然免疫信号通路、IFN诱生和抗病毒效应的影响,同时以此为基础探索优化干扰素治疗及治愈慢性乙肝的新型措施和手段。本文重点介绍了作者所在课题组的研究工作,并对未来发展提出了展望。

Hepatitis B virus （HBV） infection has been one of the most important public health problems, however, no complete cure is currently available. Although interferon （IFN）-a has been clinically used as a drug for chronic hepatitis B therapy because of its advantages including a higher rate of HBsAg/HBeAg seroconversion and a lower rate of recurrence after cessation of treatment, only 20% -40 % of patients respond well to IFN therapy, thus hampering its clinical application. In recent years, based on the in vitro HBV replication and infection cell models, animal models and patient cohort with hepatitis B and by using a variety of methods, studies have been made. On the one hand, to identify new mechanisms underlying the IFN- and IFN-induced genes-mediated anti-HBV activities and signaling transduction, on the other hand？ to reveal the effect and mechanisms of HBV replication and viral proteins in regulating the innate immune signaling pathways and IFN induction and antiviral action, based on which new strategies and approaches for optimization of IFN-based therapy and for a HBVcure have been further explored. This review mainly introduces the research findings of author ？s group and the future development is prospected.