[HTML][HTML] HIV-1 integration landscape during latent and active infection

LB Cohn, IT Silva, TY Oliveira, RA Rosales, EH Parrish… - Cell, 2015 - cell.com
LB Cohn, IT Silva, TY Oliveira, RA Rosales, EH Parrish, GH Learn, BH Hahn, JL Czartoski…
Cell, 2015cell.com
The barrier to curing HIV-1 is thought to reside primarily in CD4+ T cells containing silent
proviruses. To characterize these latently infected cells, we studied the integration profile of
HIV-1 in viremic progressors, individuals receiving antiretroviral therapy, and viremic
controllers. Clonally expanded T cells represented the majority of all integrations and
increased during therapy. However, none of the 75 expanded T cell clones assayed
contained intact virus. In contrast, the cells bearing single integration events decreased in …
Summary
The barrier to curing HIV-1 is thought to reside primarily in CD4+ T cells containing silent proviruses. To characterize these latently infected cells, we studied the integration profile of HIV-1 in viremic progressors, individuals receiving antiretroviral therapy, and viremic controllers. Clonally expanded T cells represented the majority of all integrations and increased during therapy. However, none of the 75 expanded T cell clones assayed contained intact virus. In contrast, the cells bearing single integration events decreased in frequency over time on therapy, and the surviving cells were enriched for HIV-1 integration in silent regions of the genome. Finally, there was a strong preference for integration into, or in close proximity to, Alu repeats, which were also enriched in local hotspots for integration. The data indicate that dividing clonally expanded T cells contain defective proviruses and that the replication-competent reservoir is primarily found in CD4+ T cells that remain relatively quiescent.
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