Despite suppressive combination antiretroviral therapy (ART), latent HIV-1 proviruses persist in patients. This latent reservoir is established within 48-72 h after infection, has a long half-life^1,2, enables viral rebound when ART is interrupted, and is the major barrier to a cure for HIV-1 ³ . Latent cells are exceedingly rare in blood (∼1 per 1 × 10⁶ CD4⁺ T cells) and are typically enumerated by indirect means, such as viral outgrowth assays^4,5. We report a new strategy to purify and characterize single reactivated latent cells from HIV-1-infected individuals on suppressive ART. Surface expression of viral envelope protein was used to enrich reactivated latent T cells producing HIV RNA, and single-cell analysis was performed to identify intact virus. Reactivated latent cells produce full-length viruses that are identical to those found in viral outgrowth cultures and represent clones of in vivo expanded T cells, as determined by their T cell receptor sequence. Gene-expression analysis revealed that these cells share a transcriptional profile that includes expression of genes implicated in silencing the virus. We conclude that reactivated latent T cells isolated from blood can share a gene-expression program that allows for cell division without activation of the cell death pathways that are normally triggered by HIV-1 replication.

中文翻译：

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HIV-1 潜伏库中的克隆 CD4+ T 细胞在重新激活后显示出独特的基因谱。

尽管进行了抑制性联合抗逆转录病毒治疗 (ART)，但潜伏的 HIV-1 前病毒仍存在于患者体内。这种潜伏的水库在感染后 48-72 小时内建立，具有较长的半衰期^1,2，当 ART 中断时能够实现病毒反弹，并且是治愈 HIV-1 ³的主要障碍。潜伏细胞在血液中极为罕见（每 1 × 10 ⁶ CD4 ⁺ T 细胞约 1 个），通常通过间接方法进行计数，例如病毒生长试验^4,5. 我们报告了一种新的策略来纯化和表征来自 HIV-1 感染个体的单个重新激活的潜伏细胞，以抑制 ART。病毒包膜蛋白的表面表达用于富集重新激活的产生 HIV RNA 的潜伏 T 细胞，并进行单细胞分析以鉴定完整的病毒。重新激活的潜伏细胞产生与病毒生长培养物中发现的病毒相同的全长病毒，并代表体内扩增的 T 细胞的克隆，由其 T 细胞受体序列确定。基因表达分析显示，这些细胞共享一个转录谱，包括与沉默病毒有关的基因的表达。