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

TitleClonal CD4 T cells in the HIV-1 latent reservoir display a distinct gene profile upon reactivation.
Publication TypeJournal Article
Year of Publication2018
AuthorsCohn LB, da Silva IT, Valieris R, Huang AS, Lorenzi JCC, Cohen YZ, Pai JA, Butler AL, Caskey M, Jankovic M, Nussenzweig MC
JournalNat Med
Volume24
Issue5
Pagination604-609
Date Published05/01/2018
ISSN1546-170X
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-life, enables viral rebound when ART is interrupted, and is the major barrier to a cure for HIV-1 . Latent cells are exceedingly rare in blood (∼1 per 1 × 10 CD4 T cells) and are typically enumerated by indirect means, such as viral outgrowth assays. 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.

DOI10.1038/s41591-018-0017-7
Alternate JournalNat. Med.
PubMed ID29686423
PubMed Central IDPMC5972543
Grant ListUM1 AI126620 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
P01 AI100148 / AI / NIAID NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
U01 AI118536 / AI / NIAID NIH HHS / United States
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