Infection Biology Group, Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan.
Commun Biol. 2023 May 10;6(1):487. doi: 10.1038/s42003-023-04841-y.
Latency is a major barrier towards virus elimination in HIV-1-infected individuals. Yet, the mechanisms that contribute to the maintenance of HIV-1 latency are incompletely understood. Here we describe the Schlafen 12 protein (SLFN12) as an HIV-1 restriction factor that establishes a post-transcriptional block in HIV-1-infected cells and thereby inhibits HIV-1 replication and virus reactivation from latently infected cells. The inhibitory activity is dependent on the HIV-1 codon usage and on the SLFN12 RNase active sites. Within HIV-1-infected individuals, SLFN12 expression in PBMCs correlated with HIV-1 plasma viral loads and proviral loads suggesting a link with the general activation of the immune system. Using an RNA FISH-Flow HIV-1 reactivation assay, we demonstrate that SLFN12 expression is enriched in infected cells positive for HIV-1 transcripts but negative for HIV-1 proteins. Thus, codon-usage dependent translation inhibition of HIV-1 proteins participates in HIV-1 latency and can restrict the amount of virus release after latency reversal.
潜伏期是 HIV-1 感染者中病毒消除的主要障碍。然而，导致 HIV-1 潜伏期维持的机制尚未完全理解。在这里，我们将 Schlafen 12 蛋白（SLFN12）描述为一种 HIV-1 限制因子，它在感染 HIV-1 的细胞中建立了转录后阻断，从而抑制 HIV-1 复制和潜伏感染细胞中的病毒重新激活。抑制活性依赖于 HIV-1 密码子使用和 SLFN12 的核糖核酸酶活性位点。在 HIV-1 感染者中，PBMC 中的 SLFN12 表达与 HIV-1 血浆病毒载量和前病毒载量相关，表明与免疫系统的普遍激活有关。使用 RNA FISH-Flow HIV-1 再激活测定法，我们证明 SLFN12 表达在 HIV-1 转录本阳性但 HIV-1 蛋白阴性的感染细胞中富集。因此，依赖于密码子使用的 HIV-1 蛋白翻译抑制参与 HIV-1 潜伏期，并可限制潜伏期逆转后病毒释放的量。
