Malim M H, Cullen B R
Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
Cell. 1991 Apr 19;65(2):241-8. doi: 10.1016/0092-8674(91)90158-u.
Expression of the structural proteins of HIV-1 requires the direct interaction of the viral Rev trans-activator with its cis-acting RNA target sequence, the Rev response element or RRE. Here, we demonstrate that this specific RNA-binding event is, as expected, mediated by the conserved arginine-rich motif of Rev. However, we also show that amino acid residues located proximal to this basic domain that are critical for in vivo Rev function are dispensable for sequence-specific binding to the RRE. Instead, these sequences are required for the multimerization of Rev on the viral RRE target sequence. The observation that Rev function requires the sequential binding of multiple Rev molecules to the RRE provides a biochemical explanation for the observed threshold effect for Rev function in vivo and suggests a molecular model for the high incidence of latent infection by HIV-1.
HIV-1结构蛋白的表达需要病毒Rev反式激活因子与其顺式作用RNA靶序列（即Rev反应元件或RRE）直接相互作用。在此，我们证明，正如预期的那样，这一特定的RNA结合事件是由Rev保守的富含精氨酸基序介导的。然而，我们还表明，位于该碱性结构域附近对Rev体内功能至关重要的氨基酸残基对于与RRE的序列特异性结合是可有可无的。相反，这些序列是Rev在病毒RRE靶序列上多聚化所必需的。Rev功能需要多个Rev分子顺序结合到RRE这一观察结果为体内Rev功能的阈值效应提供了生化解释，并提示了HIV-1潜伏感染高发生率的分子模型。
