HIV-1 integration landscape during latent and active infection

Cell. 2015 Jan 29;160(3):420-32. doi: 10.1016/j.cell.2015.01.020.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alu Elements
  • CD4-Positive T-Lymphocytes / virology*
  • Clone Cells
  • Defective Viruses / genetics
  • Defective Viruses / physiology
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Immunologic Memory
  • Proviruses / physiology
  • Single-Cell Analysis
  • Virus Integration*
  • Virus Latency*