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

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

Author information

1
HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA.
2
Leidos Biomedical Research, Frederick, MD 21702, USA.
3
HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA. Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, 20122 Milan, Italy.
4
Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
5
Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111, USA.
6
HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA. hughesst@mail.nih.gov.

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.

Comment in

PMID:
24968937
PMCID:
PMC4262401
DOI:
10.1126/science.1254194
[Indexed for MEDLINE]
Free PMC Article

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