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干扰素刺激基因抗HBV感染的研究进展

练韵文 郑杏容 吴和维 高志良 陈希瑶 谢婵

引用本文:
Citation:

干扰素刺激基因抗HBV感染的研究进展

DOI: 10.3969/j.issn.1001-5256.2022.01.031
基金项目: 

中山大学5010常规项目 (2018009)

利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:练韵文负责撰文及确定文章架构; 吴和维、陈希瑶、郑杏容查阅文献并修改论文; 高志良和谢婵确定文章架构及审校。
详细信息
    通信作者:

    谢婵,xchan@mail.sysu.edu.cn

Research advances in interferon-stimulated genes in treatment of hepatitis B virus infection

Research funding: 

Sun Yat-Sen University Clinical Research 5010 Program (2018009)

  • 摘要: HBV感染与肝硬化、肝癌及肝衰竭等不良事件密切相关,严重威胁人类健康。聚乙二醇干扰素是治疗慢性乙型肝炎不可或缺的药物,干扰素刺激基因与多种病毒感染相关,但与乙型肝炎的关系及干扰素治疗乙型肝炎后的预测作用仍较少被提及。介绍了干扰素治疗慢性乙型肝炎相关的预测因素,总结了干扰素刺激基因与乙型肝炎的关系及其预测作用,为临床工作及基础研究提供参考。

     

  • 图  1  IFN级联信号通路激活ISG

    注:3种不同类型的IFN信号通过与细胞表面不同的受体结合激活胞内通路发挥作用。IFN-Ⅰ和IFN-Ⅲ分别与其受体IFNAR1、IFNAR2和IL-10R2、IFNLR1结合后,其各自受体上的TyK-2与JAK-1相互靠近结合发生磷酸化而被激活,随后进一步活化STAT1、STAT2,被磷酸化的STAT1和STAT2与IRF-9结合形成异源三聚体ISGF3,ISGF3入核与ISRE结合,激活ISG转录。IFN-Ⅱ受体IFNGR-1、IFNGR-2的胞内域分别与JAk1和JAk2激酶结合,激活JAk1、JAk2,并磷酸化STAT1、STAT2,随后活化形成同源二聚体GAF,并入核与GAS结合,诱导ISG转录。

    图  2  ISG在病毒生命周期靶向作用目标

    注:ISG蛋白干扰病毒生命周期的不同阶段。胆固醇-25-羟化酶(CH25H)可能在宿主膜融合事件期间早期影响病毒入胞; 黏液瘤抗性蛋白1 (MX1)通过阻断传入病毒颗粒的内吞运输和核糖体核衣壳的脱壳而抑制多种病毒; 干扰素诱导跨膜蛋白(IFITM)成员抑制广谱病毒内吞融合事件; TRIM5α参与抑制人类免疫缺陷病毒1 (HIV-1) RNA的脱壳; 一些ISG通过降解病毒RNA和/或阻断病毒mRNA的翻译来抑制病毒,如人体2′-5′寡聚腺苷酸合成酶(2′-5′OAS)家族、蛋白激酶(PKR)、锌指抗病毒蛋白(ZAP)等; TRIM22抑制病毒的转录、复制或病毒蛋白质运输到质膜; ISG15抑制病毒翻译、复制或胞吐,如蝮蛇已被证明能抑制病毒复制或病毒在质膜上出芽。Tetherin将成熟的病毒颗粒诱捕到质膜上,从而抑制病毒的释放,并广泛作用于许多包膜病毒。

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  • 收稿日期:  2021-06-04
  • 录用日期:  2021-06-21
  • 出版日期:  2022-01-20
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