Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center of University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Antiviral Res. 2011 Jan;89(1):43-53. doi: 10.1016/j.antiviral.2010.11.005. Epub 2010 Nov 18.
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.
在这项研究中，我们测试了通过稳定的 RNAi 介导的细胞共因子敲低是否可以抑制 HIV-1 复制。生成了能够表达针对 30 种候选共因子的 shRNA 的细胞系，这些候选共因子在病毒复制周期的不同步骤中都有涉及，并分析了它们对细胞活力和 HIV-1 复制的抑制作用。对于其中一半的候选共因子，我们获得了对病毒复制敏感性降低的敲低细胞系。对于三种共因子（ALIX、ATG16 和 TRBP），细胞系对 HIV-1 复制的抗性长达 2 个月。使用这些细胞，我们可以测试 HIV-1 无法逃避细胞共因子的 RNAi 介导抑制的假设，实际上并未检测到这种逃避。
