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	Efficient inhibition of HIV-1 replication by an artificial polycistronic miRNA construct
	Zhang, Tao ; Cheng, Tong ; Wei, Lihua ; Cai, Yijun ; Yeo, Anthony Et ; Han, Jiahuai ; Yuan, Y. Adam ; Zhang, Jun ; Zhang J(张军) ; Xia, Ningshao ; Xia NS(夏宁邵)
	2012-06-18
关键词	Artificial polycistronic transcript HIV replication inhibition Viral escape RNA interference siRNA
英文摘要	Background: RNA interference (RNAi) has been used as a promising approach to inhibit human immunodeficiency virus type 1 (HIV-1) replication for both in vitro and in vivo animal models. However, HIV-1 escape mutants after RNAi treatment have been reported. Expressing multiple small interfering RNAs (siRNAs) against conserved viral sequences can serve as a genetic barrier for viral escape, and optimization of the efficiency of this process was the aim of this study. Results: An artificial polycistronic transcript driven by a CMV promoter was designed to inhibit HIV-1 replication. The artificial polycistronic transcript contained two pre-miR-30a backbones and one pre-miR-155 backbone, which are linked by a sequence derived from antisense RNA sequence targeting the HIV-1 env gene. Our results demonstrated that this artificial polycistronic transcript simultaneously expresses three anti-HIV siRNAs and efficiently inhibits HIV-1 replication. In addition, the biosafety of MT-4 cells expressing this polycistronic miRNA transcript was evaluated, and no apparent impacts on cell proliferation rate, interferon response, and interruption of native miRNA processing were observed. Conclusions: The strategy described here to generate an artificial polycistronic transcript to inhibit viral replication provided an opportunity to select and optimize many factors to yield highly efficient constructs expressing multiple siRNAs against viral infection.; National Natural Science Foundation [30500092, 30600106, 30870514]; Project 863 [2006AA020905, 2006AA02A209]; Key Program in Infectious Diseases [2008ZX10004-015]; Project 111 of the Ministry of Education, People's Republic of China [B06016]; Ministry of Education, Singapore [T208A3124]
语种	英语
出版者	BIOMED CENTRAL LTD
内容类型	期刊论文
源URL	[http://dx.doi.org/10.1186/1743-422X-9-118]
专题	公共卫生－已发表论文
推荐引用方式 GB/T 7714	Zhang, Tao,Cheng, Tong,Wei, Lihua,et al. Efficient inhibition of HIV-1 replication by an artificial polycistronic miRNA construct[J],2012.
APA	Zhang, Tao.,Cheng, Tong.,Wei, Lihua.,Cai, Yijun.,Yeo, Anthony Et.,...&夏宁邵.(2012).Efficient inhibition of HIV-1 replication by an artificial polycistronic miRNA construct..
MLA	Zhang, Tao,et al."Efficient inhibition of HIV-1 replication by an artificial polycistronic miRNA construct".(2012).

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