Adenovirus-vectored shRNAs targeted to the highly conserved regions of VP1 and 2B in tandem inhibits replication of foot-and-mouth disease virus both in vitro and in vivo

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• 作者：Yan-Fang Xu¹ ; Hai-Yan Shen¹ ; Ming-Qiu Zhao ; Li-Jun Chen ; Yin-Guang Li ; Ming Liao ; Jun-Tao Jia ; Ying-Ran Lv ; Lin Yi ; Jin-Ding Chen ; ^{jdchen@scau.edu.cn}
• 关键词：Foot-and-mouth disease virus ; Small interfering RNA ; Adenovirus ; VP1 gene ; 2B gene
• 刊名：Journal of Virological Methods
• 出版年：2012
• 期刊代码：180_01660934
• 类别：med
• 出版时间：April, 2012
• 卷：181
• 期：1
• 页码：51-58
• 文件大小：847 K

摘要

Foot-and-mouth disease is a highly contagious and economically important disease of cloven-hoofed animals. RNA interference (RNAi) can be used as a rapid and specific antiviral approach. It was shown that treatment with recombinant adenovirus (Ad_VP1-2B) carrying shRNAs targeted to the VP1 and 2B genes of FMDV expressed in tandem had marked antiviral effects against FMDV both in IBRS-2 cells and guinea pigs. Treatment with Ad_VP1-2B both before and after FMDV infection was most effective in IBRS-2 cells, as the FMDV RNA transcripts could not be detected within 48 h post-challenge (hpc), and the viral RNA copy number at 72 hpc was only 0.02%of that in the positive control group. Delivery of Ad_VP1-2B reduced significantly the susceptibility of guinea pigs to FMDV infection. All guinea pigs were protected within 3 days post challenge (dpc) when they were injected twice with the same dose of Ad_VP1-2B, and a third treatment with the same dose of Ad_VP1-2B at 3 dpc was necessary to confer longer lasting protection (up to 6 dpc). In conclusion, application of such a adenovirus vector to inhibit more than one viral gene may be an advantageous method for prevention and therapy of FMDV infection.