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.

中文翻译：

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超越整合：HIV-1 整合酶在病毒粒子形态发生中的新兴作用。


HIV-1 整合酶 (IN) 通过将逆转录病毒 DNA 整合到宿主染色体中，在病毒生命周期中发挥着关键作用。 IN 的这一功能已得到充分研究，所获得的知识已为小分子抑制剂的设计提供了信息，这些抑制剂现已构成抗逆转录病毒治疗方案的关键组成部分。最近的发现表明，IN 在人类免疫缺陷病毒 1 型 (HIV-1) 复制中具有尚未充分研究但同样重要的第二种功能。这涉及 IN 与病毒颗粒中病毒 RNA 基因组的结合，这对于病毒颗粒的正常成熟和形态发生是必需的。抑制IN与病毒RNA基因组的结合会导致病毒基因组在病毒颗粒内错误定位，并在靶细胞中过早暴露和降解。 IN 在整合和病毒粒子形态发生中的作用具有许多共同的要素，包括与病毒核酸的相互作用以及高级 IN 多聚体的组装。在此，我们在 HIV-1 生命周期的背景下描述了 IN 的这两个功能，IN 如何通过主要结构蛋白 Gag 协调与病毒基因组的结合，并讨论了针对 IN 在病毒粒子形态发生中的第二个作用的价值。