Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, 1919 route de Mende, 34293 Montpellier cedex 5, France; Université de Montpellier, 163 rue Auguste Broussonnet, 34090 Montpellier, France.
Laboratoire de Virologie, AP-HP Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Université Paris Diderot, Sorbonne Paris Cité, EA4409, 75018, Paris, France.
Sci Rep. 2017 Mar 27;7:45214. doi: 10.1038/srep45214.
HIV-2 groups have emerged from sooty mangabey SIV and entered the human population in Africa on several separate occasions. Compared to world pandemic HIV-1 that arose from the chimpanzee SIVcpz virus, the SIVsm-derived HIV-2, largely confined to West Africa, is less replicative, less transmissible and less pathogenic. Here, we evaluated the interactions between host cellular factors, which control HIV-1 infection and target the capsid, and HIV-2 capsids obtained from primary isolates from patients with different disease progression status. We showed that, like HIV-1, all HIV-2 CA we tested exhibited a dependence on cyclophilin A. However, we observed no correlation between HIV-2 viremia and susceptibility to hu-TRIM5alpha or dependence to CypA. Finally, we found that all CA from HIV-2 primary isolates exploit Nup358 and Nup153 for nucleus transposition. Altogether, these findings indicate that the ability to use the two latter nucleoporins is essential to infection of human cells for both HIV-1 and HIV-2. This dependence provides another molecular target that could be used for antiviral strategies against both HIV-1 and 2, based on both nucleoporins.
HIV-2 组从黑长尾猴 SIV 中出现,并在非洲多次进入人类群体。与源自黑猩猩 SIVcpz 病毒的世界大流行 HIV-1 相比,主要局限于西非的 SIVsm 衍生的 HIV-2 复制能力较低、传染性较低、致病性较低。在这里,我们评估了宿主细胞因子与 HIV-1 感染和靶向衣壳的相互作用,以及来自不同疾病进展状态患者的原发性分离物中的 HIV-2 衣壳。我们表明,与 HIV-1 一样,我们测试的所有 HIV-2 CA 都表现出对亲环素 A 的依赖性。然而,我们没有观察到 HIV-2 病毒血症与 hu-TRIM5alpha 的易感性或对 CypA 的依赖性之间存在相关性。最后,我们发现 HIV-2 原发性分离物的所有 CA 都利用 Nup358 和 Nup153 进行核易位。总之,这些发现表明,使用后两个核孔蛋白的能力对于 HIV-1 和 HIV-2 感染人类细胞是必不可少的。这种依赖性为基于核孔蛋白的针对 HIV-1 和 2 的抗病毒策略提供了另一个分子靶标。