|Title||Clonal CD4 T cells in the HIV-1 latent reservoir display a distinct gene profile upon reactivation.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Cohn LB, da Silva IT, Valieris R, Huang AS, Lorenzi JCC, Cohen YZ, Pai JA, Butler AL, Caskey M, Jankovic M, Nussenzweig MC|
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.
|Alternate Journal||Nat. Med.|
|PubMed Central ID||PMC5972543|
|Grant List||UM1 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
Clonal CD4 T cells in the HIV-1 latent reservoir display a distinct gene profile upon reactivation.