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

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.

SUBMITTER: Cohn LB

PROVIDER: S-EPMC5972543 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Cohn Lillian B LB da Silva Israel T IT Valieris Renan R Huang Amy S AS Lorenzi Julio C C JCC Cohen Yehuda Z YZ Pai Joy A JA Butler Allison L AL Caskey Marina M Jankovic Mila M Nussenzweig Michel C MC

Nature medicine 20180423 5

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 ...[more]

PMID: 29686423

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Dataset Information

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

Publications

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

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