应激颗粒在冠状病毒复制中的作用及机制  

Role and Involved Mechanism of Stress Granules During Coronavirus Replication

作　　者：汪圆松 乔嘉璐 孙宾莲 胡康洪[1] WANG Yuansong;QIAO Jialu;SUN Binlian;HU Kanghong(Sino-German Biomedical Center,Cooperative Innovation Center of Industrial Fermentation(Ministry of Education&Hubei Province),National“111”Center for Cellular Regulation and Molecular Pharmaceutics,Hubei University of Technology,Wuhan 430068,China;Wuhan Institute of Biomedical Sciences,School of Medicine,Jianghan University,Wuhan 430056,China)

机构地区：[1]湖北工业大学中德生物医学中心,工业发酵省部共建协同创新中心,教育部及国家外专局“111”细胞调控与分子药物学科创新引智基地,武汉430068 [2]江汉大学医学院,江汉大学武汉生物医学研究院,武汉430056

出　　处：《病毒学报》2023年第4期1134-1141,共8页Chinese Journal of Virology

基　　金：湖北省重点研发计划项目(社会发展领域)(项目号:2022BCA018),题目:多能干细胞来源胰岛定向分化技术体系。

摘　　要：近年来多种冠状病毒感染后引发患者严重的呼吸道疾病,造成危害人类健康的严重公共卫生事件。新型冠状病毒(SARS⁃CoV⁃2)暴发以来,大量研究使得人们对冠状病毒与宿主相互作用机制有更多的了解,其中关于病毒感染后应激颗粒的形成和抗病毒作用也做了大量研究。病毒的RNA和蛋白可以激活宿主细胞内蛋白激酶R(Protein kinase R,PKR)及其下游信号,刺激应激颗粒(Stress granules,SGs)的形成,进而降低病毒在宿主细胞内所需蛋白的翻译水平,抑制病毒复制。然而冠状病毒与宿主长期博弈过程中也衍生出对抗细胞SGs的相应机制,比如利用蛋白与SGs相互作用,来抑制SGs的形成和解聚,逃逸细胞对病毒的抑制作用,保证病毒稳定复制,其中新型冠状病毒就是典型的例子。因此SGs的诱导为抗冠状病毒可能提供一个新型治疗策略。本文对冠状病毒感染抵抗细胞应激颗粒的形成促进其解聚的分子机制进行综述。In recent years,infections by various types of coronaviruses have caused severe respiratory diseases.This has resulted in serious public⁃health events that endanger human life.Since the outbreak of the novel coronavirus disease 2019(COVID⁃19),many studies have focused on the interaction mechanism between severe acute respiratory syndrome⁃coronavirus⁃2(SARS⁃CoV⁃2)and the host.Several studies have concentrated on the formation of stress granules(SGs)and antiviral effects after SARS⁃CoV⁃2 infection.The RNA and proteins of viruses can activate protein kinase R(PKR)and its downstream signals in host cells.This action stimulates SGs formation and then reduces the protein translation needed by viruses in host cells,and inhibits virus replication.However,during the long⁃term interaction between coronaviruses and the host,the corresponding mechanisms against cellular SGs have also been derived.These include the interaction between proteins and SGs to inhibit the formation and depolymerization of SGs,escape the inhibitory effect of cells on the virus,and ensure the stable replication of the virus,among which SARS⁃CoV⁃2 is a typical example.Therefore,SGs induction may provide a novel strategy for the treatment of coronavirus infections.Here,we review the research progress of the molecular mechanism by which coronavirus infection resists the formation of SGs and promotes their depolymerization.

关 键 词：新型冠状病毒(SARS⁃CoV⁃2) 蛋白激酶R(Protein kinase R PKR) 应激颗粒(Stress granules SGs) 病毒复制 先天免疫 

分 类 号：R373.1[医药卫生—病原生物学]