Cell：揭示潜伏艾滋病毒的匿身之处

marine0425030

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
  

SummaryThe 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.


链接：http://www.cell.com/abstract/S0092-8674(15)00063-X