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Effective inhibition of Japanese encephalitis virus replication by shRNAs targeting various viral genes in vitro and in vivo

文献类型： 外文期刊

作者： Shen, Ting 1 ; Liu, Ke 1 ; Miao, Denian 3 ; Cao, Ruibing 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

期刊名称：VIROLOGY （ 影响因子：3.616； 五年影响因子：3.967 ）

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收录情况： SCI

摘要： Japanese encephalitis virus (JEV) is a serious mosquito-borne flavivirus that causes acute encephalitis in humans and many animals, with a high fatality rate. RNA interference (RNAi) is an evolutionary conserved mechanism for the specific suppression of gene expression, which can be used as a reasonable antiviral strategy. In this study, 10 shRNAs targeting different regions of the JEV genome were designed, and their inhibition of viral replication in vitro and in vivo was determined. Treatment with these shRNAs significantly inhibited JEV replication in BHK-21 and SK-N-SH cells. An immunohistochemical analysis of suckling mice showed that brain sections pretreated with pGP-JE-1, pGP-JE-2 or pGP-JE-3 lacked viral particles. The survival of BALB/c mice challenged with 20 LD_(50) of the JEV NJ2008 strain at 24 h post-injection or simultaneously with pGP-JE-2 was 83.3% and 66.7%, respectively. The results demonstrated that the efficiency of gene silencing and virus inhibition varied between shRNAs to different target genes and sites. Meanwhile, the shRNA-mediated antiviral effect was dose- and time-dependent, including prophylactic and therapeutic effect on virus infection both in vitro and in vivo. The whole results indicate that these shRNAs can inhibit JEV infection sufficiently in vitro and in vivo and might be a potential new tool for controlling JEV infection.

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