HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells

Science. 2014 Jul 11;345(6193):179-83. doi: 10.1126/science.1254194. Epub 2014 Jun 26.

Abstract

The persistence of HIV-infected cells in individuals on suppressive combination antiretroviral therapy (cART) presents a major barrier for curing HIV infections. HIV integrates its DNA into many sites in the host genome; we identified 2410 integration sites in peripheral blood lymphocytes of five infected individuals on cART. About 40% of the integrations were in clonally expanded cells. Approximately 50% of the infected cells in one patient were from a single clone, and some clones persisted for many years. There were multiple independent integrations in several genes, including MKL2 and BACH2; many of these integrations were in clonally expanded cells. Our findings show that HIV integration sites can play a critical role in expansion and persistence of HIV-infected cells.

Publication types

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

MeSH terms

  • Anti-Retroviral Agents / therapeutic use
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Clone Cells / virology
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • Genome, Human
  • HIV / genetics
  • HIV / physiology*
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / virology*
  • Humans
  • RNA, Viral / analysis
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Transcription Factors / genetics*
  • Virus Integration / genetics*
  • Virus Latency / genetics*

Substances

  • Anti-Retroviral Agents
  • BACH2 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • DNA, Viral
  • MRTFB protein, human
  • RNA, Viral
  • Transcription Factors