Numerical data for Fig 5.

The HIV-1 Rev-RRE regulatory axis plays a crucial role in viral replication by facilitating the nucleo-cytoplasmic export and expression of viral mRNAs with retained introns. In this study, we investigated the impact of variation in Rev-RRE functional activity on HIV-1 replication kinetics and reactivation from latency. Using a novel HIV-1 viral vector with an interchangeable Rev cassette, we engineered viruses with two diverse Rev functional activities and demonstrated that higher Rev-RRE activity confers greater viral replication capacity while maintaining a constant level of Nef expression. In addition, a low Rev activity virus rapidly acquired a compensatory mutation in the RRE that significantly increased Rev-RRE activity and replication. In a latency model, proviruses with differing Rev-RRE activity levels varied in the efficiency of viral reactivation, affecting both initial viral release and subsequent replication kinetics. These results demonstrate that activity differences in the Rev-RRE axis among different viral isolates have important implications for HIV replication dynamics and persistence. Importantly, our findings indicate that bolstering Rev/RRE activity could be explored as part of latency reversal strategies in HIV cure efforts.人类免疫缺陷病毒1型（HIV-1）的Rev-RRE调控轴通过介导内含子滞留型病毒mRNA的核质输出与表达，在病毒复制过程中发挥关键作用。本研究探究了Rev-RRE功能活性变异对HIV-1复制动力学及潜伏病毒再激活的影响。本研究构建了携带可替换Rev基因盒的新型HIV-1病毒载体，借此工程化获得两种具有不同Rev功能活性的病毒株，实验证实：更高的Rev-RRE活性可赋予病毒更强的复制能力，同时维持Nef蛋白表达水平恒定。此外，Rev活性较低的病毒株会快速在RRE区域获得代偿性突变，该突变可显著提升Rev-RRE活性与病毒复制能力。在潜伏感染模型中，Rev-RRE活性水平各异的前病毒，其病毒再激活效率存在显著差异，该差异会同时影响初始病毒释放及后续复制动力学过程。上述结果表明，不同病毒分离株间Rev-RRE轴的活性差异，对HIV的复制动态与病毒持续感染具有重要意义。值得注意的是，本研究结果提示，增强Rev/RRE活性可作为HIV治愈研究中潜伏逆转策略的潜在探索方向。