Ramakrishnan Rajesh, Ahmad Nafees
Department of Immunobiology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, AZ 85724, USA.
Virology. 2007 Mar 1;359(1):201-11. doi: 10.1016/j.virol.2006.09.003. Epub 2006 Oct 11.
We have characterized the primary RRE sequences of HIV-1, including in vivo genetic variation and functional motifs required for Rev-RRE interactions as well as evaluated the RNA secondary structures of RRE derived from five mother-infant pairs following vertical transmission. Multiple (157) RRE sequences derived from mother-infant pairs showed that primary nucleotide sequences of RRE were highly conserved with a low degree of viral heterogeneity following vertical transmission. We found that the RRE sequences from mothers and infants folded and retained all the essential stem-loop formation required for Rev-RRE interactions. More importantly, a primary 9-nucleotide (5'-CACTATGGG-3') RRE sequence in the stem-loop B that is required for optimal Rev recognition and must be presented as a stem-bulge-stem structure was highly conserved in most of the sequences. The domains required for RRE-host protein interactions were also conserved in most of the RRE sequences. Taken together, the primary RRE sequences in the context of secondary structures were maintained and the Rev-RRE interaction domains were conserved following vertical transmission, which is consistent with a crucial role of RRE in HIV-1 pathogenesis.
我们已对HIV-1的主要Rev反应元件（RRE）序列进行了特征分析，包括体内遗传变异以及Rev与RRE相互作用所需的功能基序，还评估了垂直传播后来自五对母婴的RRE的RNA二级结构。来自母婴对的多个（157个）RRE序列显示，垂直传播后RRE的一级核苷酸序列高度保守，病毒异质性程度较低。我们发现，来自母亲和婴儿的RRE序列能够折叠并保留Rev与RRE相互作用所需的所有基本茎环结构。更重要的是，茎环B中一个9核苷酸（5'-CACTATGGG-3'）的主要RRE序列对于最佳Rev识别是必需的，且必须呈现为茎-膨出-茎结构，在大多数序列中高度保守。RRE与宿主蛋白相互作用所需的结构域在大多数RRE序列中也保守。综上所述，二级结构背景下的主要RRE序列得以维持，垂直传播后Rev与RRE的相互作用结构域保守，这与RRE在HIV-1发病机制中的关键作用一致。
