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HIV-1 Integration Landscape during Latent and Active Infection
作者: marine0425030 时间: 2015-2-3 12:07 HIV-1 Integration Landscape during Latent and Active InfectionHighlights
•Integration sequencing identifies clonally expanded and single HIV-1 integrations in human subjects
•Large clonal families of HIV-1+ cells are likely not part of the latent reservoir
•HIV-1 integrates near or into a 30 bp INT-motif found in Alu repeats
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.