A hallmark of retroviral replication is establishment of the proviral state, wherein a DNA copy of the viral RNA genome is stably incorporated into a host cell chromosome. Integrase is the viral enzyme responsible for the catalytic steps involved in this process, and integrase strand transfer inhibitors are widely used to treat people living with HIV. Over the past decade, a series of X-ray crystallography and cryogenic electron microscopy studies have revealed the structural basis of retroviral DNA integration. A variable number of integrase molecules congregate on viral DNA ends to assemble a conserved intasome core machine that facilitates integration. The structures additionally informed on the modes of integrase inhibitor action and the means by which HIV acquires drug resistance. Recent years have witnessed the development of allosteric integrase inhibitors, a highly promising class of small molecules that antagonize viral morphogenesis. In this Review, we explore recent insights into the organization and mechanism of the retroviral integration machinery and highlight open questions as well as new directions in the field.

逆转录病毒复制的标志是建立前病毒状态，其中病毒 RNA 基因组的 DNA 拷贝稳定地掺入宿主细胞染色体中。整合酶是负责参与该过程的催化步骤的病毒酶，整合酶链转移抑制剂广泛用于治疗 HIV 感染者。在过去十年中，一系列 X 射线晶体学和低温电子显微镜研究揭示了逆转录病毒 DNA 整合的结构基础。可变数量的整合酶分子聚集在病毒 DNA 末端以组装促进整合的保守整合体核心机器。这些结构还告知整合酶抑制剂作用的模式以及 HIV 获得耐药性的方式。近年来见证了变构整合酶抑制剂的发展，这是一类非常有前途的小分子，可拮抗病毒形态发生。在这篇综述中，我们探讨了最近对逆转录病毒整合机制的组织和机制的见解，并强调了该领域的未决问题和新方向。