Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Viruses. 2020 Sep 9;12(9):1005. doi: 10.3390/v12091005.
The HIV-1 integrase enzyme (IN) plays a critical role in the viral life cycle by integrating the reverse-transcribed viral DNA into the host chromosome. This function of IN has been well studied, and the knowledge gained has informed the design of small molecule inhibitors that now form key components of antiretroviral therapy regimens. Recent discoveries unveiled that IN has an under-studied yet equally vital second function in human immunodeficiency virus type 1 (HIV-1) replication. This involves IN binding to the viral RNA genome in virions, which is necessary for proper virion maturation and morphogenesis. Inhibition of IN binding to the viral RNA genome results in mislocalization of the viral genome inside the virus particle, and its premature exposure and degradation in target cells. The roles of IN in integration and virion morphogenesis share a number of common elements, including interaction with viral nucleic acids and assembly of higher-order IN multimers. Herein we describe these two functions of IN within the context of the HIV-1 life cycle, how IN binding to the viral genome is coordinated by the major structural protein, Gag, and discuss the value of targeting the second role of IN in virion morphogenesis.
HIV-1 整合酶（IN）在病毒生命周期中起着至关重要的作用，它将逆转录的病毒 DNA 整合到宿主染色体中。IN 的这一功能已经得到了充分的研究，相关知识也为小分子抑制剂的设计提供了信息，这些抑制剂现在已成为抗逆转录病毒疗法方案的重要组成部分。最近的发现揭示了 IN 在人类免疫缺陷病毒 1（HIV-1）复制中还有一个研究不足但同样重要的第二个功能。这涉及 IN 与病毒 RNA 基因组在病毒粒子中的结合，这对于病毒粒子的成熟和形态发生是必要的。IN 与病毒 RNA 基因组结合的抑制会导致病毒基因组在病毒粒子内的定位错误，以及其在靶细胞中的过早暴露和降解。IN 在整合和病毒形态发生中的作用有许多共同的要素，包括与病毒核酸的相互作用和更高阶 IN 多聚体的组装。本文将在 HIV-1 生命周期的背景下描述 IN 的这两个功能，以及 Gag 主要结构蛋白如何协调 IN 与病毒基因组的结合，并讨论靶向 IN 在病毒形态发生中的第二个作用的价值。
