Clonal CD4+ T cells in the HIV-1 latent reservoir display a distinct gene profile upon reactivation. (May 2018)

• Record Type: Journal Article
• Authors: Cohn, Lillian; Silva, Israel; Valieris, Renan; Huang, Amy; Lorenzi, Julio; Cohen, Yehuda; Pai, Joy; Butler, Allison; Caskey, Marina; Jankovic, Mila; Nussenzweig, Michel
• Is Part Of: Nature medicine. Volume 24:Number 5(2018)
• Page Start: 604
• Page End: 609
• Publication Date: 2018-05
• Subjects: Pathology, Molecular -- Periodicals; Molecular biology -- Periodicals; 610.724
• DOI: 10.1038/s41591-018-0017-7
• Languages: English
• ISSNs: 1078-8956

Abstract

Abstract 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-life1, 2, enables viral rebound when ART is interrupted, and is the major barrier to a cure for HIV-13 . 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 assays4, 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. A shared gene expression program associated with silencing HIV-1 transcription may be critical for persistence of reactivated latent CD4+ T cells in patients with HIV.