昆虫RNA沉默抗病毒机制研究进展

Advances in the mechanism of antiviral RNA silencing in insects

RNA沉默是昆虫用来抵御病毒入侵的一种普遍而又进化保守的防御机制,而昆虫病毒也会相应地编码沉默抑制子来破坏宿主的防御功能。本文主要结合果蝇的相关研究成果对昆虫RNA沉默抗病毒机制、RNA沉默抑制子的作用特征及宿主与病毒的共进化关系做一综述。研究表明,由小干扰RNA(small interfering RNAs,siRNA)介导的RNA干扰在果蝇抗病毒防御机制中发挥重要作用。果蝇中Dicer-2(Dcr-2),argonaute-2(AGO2)和双链RNA结合蛋白R2D2是siRNA干扰途径中的3个关键组分,这3个基因的缺失或突变会显著提高果蝇对RNA病毒的感受性。此外,果蝇中还鉴定了其他与RNA干扰密切相关的基因,如vasa intronic gene,aubergine,armitage,rm62和piwi,它们在抗病毒感染中同样发挥重要作用。果蝇病毒中已鉴定出3种RNA沉默病毒抑制子(viralsuppressors of RNAi,VSRs),分别为果蝇FHV病毒沉默抑制子FHV-B2、果蝇C病毒沉默抑制子DCV-1A及果蝇CrPV病毒沉默抑制子CrPV-1A。FHV-B2和DCV-1A通过与dsRNA或siRNA结合抑制RNA沉默,而CrPV-1A通过与AGO2结合阻止RISC的形成抑制RNA沉默。在漫长的进化过程中,病毒和宿主相互博弈,协同进化。昆虫抗病毒沉默途径中的关键组分通过保持持续和快速进化来对抗高度变异的VSRs。

RNA silencing is identified as a general and evolutionarily conserved antiviral defense mechanism in insects.Meanwhile,viruses adapt the strategy by encoding suppressors of RNA silencing to counter the host-defense.Based on the related achievements in Drosophila,this article reviews the mechanism of antiviral RNA silencing,the characteristics and functions of RNA silencing suppressors,and the coevolution between hosts and viruses.Studies showed that RNA interference mediated by siRNA（small interfering RNAs,siRNA） plays a vital role in antiviral defense in Drosophila.Dicer-2（Dcr-2） ,argonaute-2（AGO2） and R2D2 are three key components in siRNA pathway in Drosophila.Flies with these three genes knockdowned were hypersensitive to RNA virus infection.Additionally,several core genes involved in RNA interference were identified,including vasa intronic gene,aubergine,armitage,rm62 and piwi,which also play roles in antiviral defense in Drosophila.Three viral suppressors of RNAi（VSRs） have been identified in Drosophila viruses,i.e.,FHV-B2,DCV-1A and CrPV-1A.FHV-B2 and DCV-1A inhibit RNA silencing by binding dsRNA or siRNA while CrPV-1A by targeting AGO2.During the boundless process of evolution,the hosts and viruses counter each other as well as coevolve.Components of antiviral silencing against highly diverse VSRs should be continuously and rapidly evolving.