A large number of human immunodeficiency virus 1 (HIV-1) integrase (IN) alterations, referred to as class II substitutions, exhibit pleiotropic effects during virus replication. However, the underlying mechanism for the class II phenotype is not known. Here we demonstrate that all tested class II IN substitutions compromised IN-RNA binding in virions by one of the three distinct mechanisms: (i) markedly reducing IN levels thus precluding the formation of IN complexes with viral RNA; (ii) adversely affecting functional IN multimerization and consequently impairing IN binding to viral RNA; and (iii) directly compromising IN-RNA interactions without substantially affecting IN levels or functional IN multimerization. Inhibition of IN-RNA interactions resulted in the mislocalization of viral ribonucleoprotein complexes outside the capsid lattice, which led to premature degradation of the viral genome and IN in target cells. Collectively, our studies uncover causal mechanisms for the class II phenotype and highlight an essential role of IN-RNA interactions for accurate virion maturation.

中文翻译：

---

整合酶-RNA 相互作用强调整合酶在 HIV-1 病毒粒子形态发生中的关键作用

大量人类免疫缺陷病毒 1 (HIV-1) 整合酶 (IN) 改变，称为 II 类替代，在病毒复制过程中表现出多效性。然而，II 类表型的潜在机制尚不清楚。在这里，我们证明所有测试的 II 类 IN 替换都通过三种不同机制之一破坏了病毒粒子中的 IN-RNA 结合：(i) 显着降低了 IN 水平，从而阻止了与病毒 RNA 形成 IN 复合物；(ii) 对功能性 IN 多聚化产生不利影响，从而削弱 IN 与病毒 RNA 的结合；(iii) 直接损害 IN-RNA 相互作用而不显着影响 IN 水平或功能性 IN 多聚化。IN-RNA相互作用的抑制导致病毒核糖核蛋白复合物在衣壳晶格外的错误定位，这导致病毒基因组和靶细胞中的 IN 过早降解。总的来说，我们的研究揭示了 II 类表型的因果机制，并强调了 IN-RNA 相互作用对准确病毒体成熟的重要作用。