Blissenbach Maik, Grewe Bastian, Hoffmann Bianca, Brandt Sabine, Uberla Klaus
Department of Molecular and Medical Virology, Ruhr-University Bochum, Universitaetsstr. 150, D-44780 Bochum, Germany.
J Virol. 2010 Jul;84(13):6598-604. doi: 10.1128/JVI.02264-09. Epub 2010 Apr 28.
Although the viral Rev protein is necessary for HIV replication, its main function in the viral replication cycle has been controversial. Reinvestigating the effect of Rev on the HIV-1 RNA distribution in various cell lines and primary cells revealed that Rev enhanced cytoplasmic levels of the unspliced HIV-1 RNA, mostly 3- to 12-fold, while encapsidation of the RNA and viral infectivity could be stimulated >1,000-fold. Although this clearly questions the general notion that the nuclear export of viral RNAs is the major function of Rev, mechanistically encapsidation seems to be linked to nuclear export, since the tethering of the nuclear export factor TAP to the HIV-1 RNA also enhanced encapsidation. Interference with the formation of an inhibitory ribonucleoprotein complex in the nucleus could lead to enhanced accessibility of the cytoplasmic HIV-1 RNA for translation and encapsidation. This might explain why Rev and tethered TAP exert the same pattern of pleiotropic effects.
尽管病毒Rev蛋白对于HIV复制是必需的，但其在病毒复制周期中的主要功能一直存在争议。重新研究Rev对各种细胞系和原代细胞中HIV-1 RNA分布的影响发现，Rev增强了未剪接的HIV-1 RNA的细胞质水平，大多提高了3至12倍，而RNA的包装和病毒感染性可被刺激超过1000倍。尽管这显然质疑了病毒RNA的核输出是Rev主要功能的普遍观念，但从机制上讲，包装似乎与核输出相关，因为核输出因子TAP与HIV-1 RNA的连接也增强了包装。干扰细胞核中抑制性核糖核蛋白复合物的形成可能导致细胞质中HIV-1 RNA用于翻译和包装的可及性增加。这可能解释了为什么Rev和连接的TAP发挥相同模式的多效性作用。
