基于GEO数据分析的猪病毒源siRNA  

Analysis of siRNAs Derived from Swine-originated Viruses Based on GEO Data

作　　者：吴耀棠 吴洋 赵晋豪 卢丹青 林建[1] 杨倩[1] WU Yaotang;WU Yang;ZHAO Jinhao;LU Danqing;LIN Jian;YANG Qian(College of Veterinary Medicine,Nanjing Agricultural University,Nanjing 2095,China;College ofLife Sciences,Nanjing AgriculturalUniversity,Nanjing 210095,China)

机构地区：[1]南京农业大学动物医学院,南京210095 [2]南京农业大学生命科学学院,南京210095

出　　处：《病毒学报》2023年第2期499-508,共10页Chinese Journal of Virology

基　　金：国家自然科学基金(项目号:32072835),鸡传染性支气管炎病毒抑制鸡树突状细胞抗原提呈机理的研究;国家重点研发计划(项目号:2021YFD1801105),宿主对畜禽冠状病毒的免疫应答和免疫保护机制;江苏省自然科学基金(项目号:BK20190077),新型黏膜免疫增强剂的开发及其调控鸡树突状细胞抗原递呈分子机制的研究。

摘　　要：RNA干扰(RNA interference,RNAi)是宿主细胞抗病毒的关键方法之一,其核心切割酶Dicer会将病毒复制过程中产生的双链RNA切割成长度为21-23 nt小干扰RNA(small interfering RNA,siRNA)。病毒源siRNA可直接靶向降解病毒的mRNA,阻断病毒复制。本研究一方面筛选NCBI GEO(National Center for Biotechnology Information Gene Expression Omnibus)数据库中有关猪病毒感染后产生的小RNA序列,分析比对病毒vsiRNA以探讨vsiRNA数量和其在病毒基因区域的存在规律。研究结果表明RNAi系统中Dicer对正链RNA病毒有一定的切割偏好性,并且可以识别与切割DNA病毒转录过程中产生的双链RNA。另一方面,本研究发现猪流行性腹泻病毒(Porcine epidemic diarrhea virus,PEDV)感染猪骨髓源树突状细胞后,宿主细胞的IFN-α、IFN-β与Dicer的表达量均显著下调,表明PEDV通过抑制IFN及RNAi的产生来实现免疫逃避。综上,本研究以猪相关病毒感染细胞时所产生的vsiRNA为切入点,探讨RNAi在抗病毒过程中的作用,为猪相关疫病的研究以及防控提供一种新的思路。RNA interference(RNAi) is a major antiviral process of host cells. The core enzyme Dicer cuts the double-stranded RNA produced during virus replication into small interfering RNAs(siRNAs) of length 21–23nt. Viral siRNAs can target the degradation of viral mRNA directly and block viral replication. We screened and analyzed the small RNA sequences related to porcine viral infections in the National Center for Biotechnology Information Gene Expression Omnibus database. Meanwhile, we aligned virus small interfering(vsi)RNAs to explore the number of vsiRNAs and their distribution in virus gene regions. We discovered that Dicer in the RNAi system:(i) preferentially cleaved positive-stranded RNA viruses;and(i) recognized and cleaved the double-stranded RNA produced during DNA transcription of the virus. Expression of interferon(IFN)-α, IFN-β, and Dicer was downregulated when the porcine epidemic diarrhea virus(PEDV) infected porcine bone marrow-derived dendritic cells, which indicated that the PEDV achieved immune evasion by inhibiting the production of IFN and RNAi. In this study, the vsiRNAs produced by swine-associated virus-infected cells were used as entry points to explore the role of RNAi in anti-viral actions. Use of vsiRNAs provided new ideas for the research and prevention of swine-related diseases.

关 键 词：RNA干扰 抗病毒系统 生物信息分析 SIRNA 

分 类 号：S855.3[农业科学—临床兽医学]