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Lentivirus-mediated RNA interference against Japanese encephalitis virus infection in vitro and in vivo

文献类型： 外文期刊

作者： Shen, Ting 1 ; Liu, Ke 2 ; Miao, Denian 3 ; Cao, Ruibing 1 ; Zhou, Bin 1 ; Chen, Puyan 1 ;

作者机构： 1.Nanjing Agr Univ, Coll Vet Med, Minist Agr, Key Lab Anim Dis Diag & Immunol, Nanjing 210095, Jiangsu, Peoples R China

2.Chinese Acad Agr Sci, Shanghai Vet Res Inst, Shanghai 200241, Peoples R China

3.Shanghai Acad Agr Sci, Inst Anim Husb & Vet Sci, Shanghai 201106, Peoples R China

关键词： JEV;Lentiviral shRNA;Antiviral;Inflammatory response;In vitro and in vivo

期刊名称：ANTIVIRAL RESEARCH （ 影响因子：5.97； 五年影响因子：5.801 ）

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收录情况： SCI

摘要： Japanese encephalitis virus, a serious mosquito-borne flavivirus, causes acute encephalitis in humans and many animals, with a high fatality rate. RNA interference is a reasonable antiviral mechanism for target gene silencing. In this study, four lentiviral shRNAs (LV-E1, LV-E2, LV-NS3 and LV-NS4b) were constructed. The results showed that four recombinant lentiviruses suppressed JEV replication in vitro. Through treatment with LV-E1 or LV-E2, the TCID_(50) values were reduced by 10~3-fold during 120h post-challenge; the relative expression of viral mRNA was <7% or 13% in mouse and human neuroblas-toma cells. Lentiviral shRNAs displayed robust inhibitory activity in various cells and against different genotypes of JEV. In vivo, pre-treatments of LV-E1 or LV-E2 resulted in no viral particles being observed in suckling mice brain sections. For 21 days of observation, 100% of mice were protected against lethal JEV injection by two pre-treatments with'LV-E1 or LV-E2; the survival of the mice pre-challenged with lethal JEV was 88.3%/66.7% by treatment with LV-E1 or LV-E2. LV-E1 and LV-E2 suppressed the induction of inflammatory mediators effectively in neuroblastoma cells and mice. Lentiviral shRNAs significantly inhibit JEV infection for long-term in vitro and in vivo and effectively reduce the inflammatory response and relieve encephalitis symptoms, highlighting the feasibility of using lentivirus-mediated RNAi for potential therapy in JEV infection.

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