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Nat Med. 2018 May;24(5):604-609. doi: 10.1038/s41591-018-0017-7. Epub 2018 Apr 23.

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

Author information

1
Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA.
2
Laboratory of Computational Biology and Bioinformatics, A.C. Camargo Cancer Center (CIPE), Sao Paulo, Brazil.
3
Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA. nussen@rockefeller.edu.
4
Howard Hughes Medical Institute (HHMI), Rockefeller University, New York, NY, USA. nussen@rockefeller.edu.

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-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 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.

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