Long-term inhibition of HIV-1 replication with RNA interference against cellular co-factors

被引:44
作者
Eekels, Julia J. M. [1 ]
Geerts, Dirk [2 ]
Jeeninga, Rienk E. [1 ]
Berkhout, Ben [1 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam, Lab Expt Virol,Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Human Genet, NL-1105 AZ Amsterdam, Netherlands
关键词
HIV-1; Cellular co-factors; RNAi; shRNA; Gene silencing; IMMUNODEFICIENCY-VIRUS TYPE-1; BINDING PROTEIN; HUMAN HOMOLOG; T-CELLS; EXPRESSION; INFECTION; ESCAPE; IDENTIFICATION; TRANSCRIPTION; INTEGRASE;
D O I
10.1016/j.antiviral.2010.11.005
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
In this study we tested whether HIV-1 replication could be inhibited by stable RNAi-mediated knockdown of cellular co-factors. Cell lines capable of expressing shRNAs against 30 candidate co-factors implicated at different steps of the viral replication cycle were generated and analyzed for effects on cell viability and inhibition of HIV-1 replication. For half of these candidate co-factors we obtained knockdown cell lines that are less susceptible to virus replication. For three co-factors (ALIX, ATG16 and TRBP) the cell lines were resistant to HIV-1 replication for up to 2 months. With these cells we could test the hypothesis that HIV-1 is not able to escape from RNAi-mediated suppression of cellular co-factors, which was indeed not detected. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:43 / 53
页数:11
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