Evaluation of a combinatorial RNAi lentivirus vector targeting foot-and-mouth disease virus in vitro and in vivo

文献类型： 外文期刊

第一作者： Zhang, Xiaoxi

作者： Zhang, Xiaoxi;Zhou, Yu;Li, Xiangping;Yang, Fan;Liu, Qingyou;Shi, Deshun;Zhang, Xiaoxi;Zheng, Haixue;Xu, Minjun

作者机构：

关键词： foot-and-mouth disease virus;multiple short hairpin RNA;lentiviral vector

期刊名称：MOLECULAR MEDICINE REPORTS （ 影响因子：2.952； 五年影响因子：2.754 ）

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收录情况： SCI

摘要： Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals, which leads to serious economical losses. FMDV is not adequately controlled by vaccination or biosecurity measures. To generate genetically modified FMDV-resistant animals, a combinatorial expression cassette producing three short hairpin (sh) RNAs was constructed using the lentivirus (LV) vector, LV-3shRNA. The three shRNAs were expressed under the regulation of DNA polymerase III promoters from a buffalo and a bovine source, with one targeted to the non-structural protein 3B, and the other two targeted to the viral polymerase protein 3D of FMDV, respectively. The role of LV-3shRNA in the inhibition of the replication of FMDV was determined in BHK-21 cells and in suckling mice. The results revealed that LV-3shRNA reduced viral growth 3-fold (24 h post-infection) when the cells were challenged with 10(7)-times the tissue culture infective dose (TCID50)/ml of 0 serotype FMDV. The suckling mice pretreated with LV-3shRNA were completely protected on administration of 5-times the dose of FMDV otherwise sufficient to kill 50% of the experimental animals (LD50). These results demonstrated that the LV-mediated dual expression of three FMDV-specific shRNAs provided a novel strategy towards combating FMDV, which facilitates the permanent introduction of novel disease-resistance traits into the buffalo and bovine genomes in the future.

分类号： R3

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