发热伴血小板减少综合征病毒微基因组模型的构建与应用

Construction and Application of A Minigenome System for the Severe Fever with Thrombocytopenia Syndrome Virus

发热伴血小板减少综合征病毒(Severe fever with thrombocytopenia syndrome bunyavirus,SFTSV)是一种新发蜱传布尼亚病毒,人群普遍易感,病死率高,目前没有针对SFTSV感染的特异性疫苗和治疗药物。为开发针对它的研究方法和工具,本研究用反向遗传学方法构建了基于SFTSV S片段非编码区的微基因组模型,并利用该模型验证了广谱RNA病毒RdRp抑制剂,法匹拉韦(Favipiravir,T⁃705)的活性。在表达报告基因Gluc的微基因组模型中,T⁃705表现出显著的抑制活性(IC_(50)=3.17μmol/L),且具有良好的剂量相关性(r^(2)=0.95),证明了该微基因组模型用于SFTSV RdRp抑制剂筛选的可行性。

The severe fever with thrombocytopenia syndrome virus(SFTSV)is an emerging tick⁃borne bunyavirus.The general population is susceptible,and a high fatality rate has been noted.Specific vaccines or medicinal agents for the treatment of SFTSV infection are lacking.There is an urgent need to develop countermeasures against SFTSV infection.We established a minigenome system for the SFTSV based on the non⁃coding region of the S fragment by means of reverse genetics.We verified the feasibility for screening SFTSV inhibitors with favipiravir(T⁃705),a broad⁃spectrum RNA⁃dependent RNA polymerase(RdRp)inhibitor.We found expression of the reporter gene Gluc to be inhibited by T⁃705(IC_(50)=3.17μmol/L),with a good correlation with the dose(r^(2)=0.95).Our minigenome model showed good sensitivity and applicability for screening RdRp inhibitors.