Silencing of HIV-1 gag gene from epidemic strains among men who have sex with men (MSM) in Tianjin, China by a broad-spectrum short hairpin RNA

被引：0
作者：
Liang Z. [1 ]
Wang X. [2 ]
Li H. [1 ]
Liu B. [1 ]
Zhao X. [1 ]
Liu C. [1 ]
Kong X.-H. [1 ]
机构：
[1] School of Medicine, Nankai University, 94 Weijin Road, Nankai District, Tianjin
[2] Tianjin Centers for Disease Control and Prevention, Tianjin
来源：
VirusDisease | 2014年 / 25卷 / 3期
基金：
中国国家自然科学基金;
关键词：
gag; HIV-1; MSM; shRNA;
D O I：
10.1007/s13337-014-0209-9
中图分类号：
学科分类号：
摘要：
RNA interference (RNAi) has been successfully used as a promising method to inhibit the replication of different viruses, including human immunodeficiency virus (HIV). Gene mutation is a hurdle for the anti-HIV by RNAi. Although prone to mutation, some genes are conserved and limited in functionally important regions. The gag gene is conserved in different subtypes and plays an important role in the assembly of HIV viral particle. Here, we identified subtypes and conserved sequences within forty-four gag genes from the epidemic strains among men who have sex with men. Three subtypes of gag gene, including CRF01_AE (47.7 %), CRF07_BC (40.9 %) and B (11.4 %) were analyzed by online blast. We designed five small hairpin RNAs (shRNAs) based on the conserved sequences. The gag–EGFP fusion transcript reporter system was used to select the most efficient shRNA. Among the five candidate shRNAs, gag-shRNA-3 represented a broad-spectrum inhibition against all chosen targets. This broad-spectrum shRNA diminished the titer of subtypes B and C of HIV-1 for a hundred orders of magnitude. The gag-shRNA-3 described here is a potential therapeutic agent in the HIV-1 gene therapy. © 2014, Indian Virological Society.
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收藏
页码：294 / 301
页数：7
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