Understanding the viral–host cell interface during HIV-1 infection is a prerequisite for the development of innovative antiviral therapies. Here we show that the suppressor of G2 allele of skp1 (SUGT1) is a permissive factor for human immunodeficiency virus (HIV)-1 infection. Expression of SUGT1 increases in infected cells on human brain sections and in permissive host cells. We found that SUGT1 determines the permissiveness to infection of lymphocytes and macrophages by modulating the nuclear import of the viral genome. More importantly, SUGT1 stabilizes the microtubule plus-ends (+MTs) of host cells (through the modulation of microtubule acetylation and the formation of end-binding protein 1 (EB1) comets). This effect on microtubules favors HIV-1 retrograde trafficking and replication. SUGT1 depletion impairs the replication of HIV-1 patient primary isolates and mutant virus that is resistant to raltegravir antiretroviral agent. Altogether our results identify SUGT1 as a cellular factor involved in the post-entry steps of HIV-1 infection that may be targeted for new therapeutic approaches.

了解 HIV-1 感染期间的病毒-宿主细胞界面是开发创新抗病毒疗法的先决条件。这里我们展示了skp1的 G2 等位基因的抑制子(SUGT1) 是人类免疫缺陷病毒 (HIV)-1 感染的允许因素。SUGT1 的表达在人脑切片上的受感染细胞和允许宿主细胞中增加。我们发现 SUGT1 通过调节病毒基因组的核输入来决定对淋巴细胞和巨噬细胞感染的容许性。更重要的是，SUGT1 稳定宿主细胞的微管正端 (+MTs)（通过调节微管乙酰化和末端结合蛋白 1 (EB1) 彗星的形成）。这种对微管的影响有利于 HIV-1 逆行运输和复制。SUGT1 耗竭会损害 HIV-1 患者原代分离株和对拉替拉韦抗逆转录病毒药物具有抗性的突变病毒的复制。