Induction of protection against foot-and-mouth disease virus in cell culture and transgenic suckling mice by miRNA targeting integrin alpha v receptor

文献类型： 外文期刊

第一作者： Du, Junzheng

作者： Du, Junzheng;Gao, Shandian;Luo, Jihuai;Hao, Chunxia;Yang, Bo;Lin, Tong;Shao, Junjun;Cong, Guozheng;Chang, Huiyun;Guo, Xinbing;Gong, Xiuli;Guo, Xinbing;Gong, Xiuli;Guo, Xinbing;Gong, Xiuli

作者机构：

关键词： RNAi;FMDV receptor;Artificial miRNA;Transgenic suckling mouse;Virus infection

期刊名称：JOURNAL OF BIOTECHNOLOGY （ 影响因子：3.307； 五年影响因子：3.778 ）

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收录情况： SCI

摘要： Foot-and-mouth disease virus (FMDV) is an RNA virus that causes a highly contagious disease in domestic and wild cloven-hoofed animals. Although vaccination has been used to protect animals against FMDV, there are shortcomings in the efficacy of the available vaccines. RNA interference (RNAi) is triggered by small RNA molecules, including short interfering RNAs and microRNAs (miRNAs), and the use of RNAi-based methods have demonstrated promise as an alternative method of controlling the transmission of FMDV. However, the method of delivery, short duration of siRNA and miRNA in vivo, and the genetic variability of FMDV confound the use of RNAi-based strategies for FMDV control. FMDV has been shown to exploit host-cell integrins as cell-surface receptors to initiate infection. We selected the gene for the integrin alpha v subunit as an RNAi target, and constructed three alpha v-specific miRNA expression plasmids. The effects of these miRNAs on FMDV infection were examined in PK-15 cells and transgenic suckling mice. In PK-15 cells, the expression of the alpha v-specific miRNAs significantly inhibited the expression of integrin alpha v receptor and decreased FMDV infection. The transgenic mice were generated by integrating the alpha v-specific miRNA expression cassette using pronuclear microinjection. When challenged with a dose of FMDV ten times greater than the LD50, the survival rate of transgenic suckling mice was approximately sixfold higher than that of their non-transgenic littermates, indicating that the interference of the miRNAs significantly reduced FMDV infection in the transgenic mice. This is the first report of limiting FMDV attachment to cellular receptors using miRNA-mediated gene knock down of cell-surface receptors to significantly reduce FMDV infection in cell culture and transgenic suckling mice. (C) 2014 Elsevier B.V. All rights reserved.

分类号： Q81

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