title: HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells.
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.
authors: HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA.
authors: F
authors: F
authors: Maldarelli
authors: Leidos Biomedical Research, Frederick, MD 21702, USA.
authors: X
authors: X
authors: Wu
authors: Leidos Biomedical Research, Frederick, MD 21702, USA.
authors: L
authors: L
authors: Su
authors: 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.
authors: F R
authors: FR
authors: Simonetti
authors: Leidos Biomedical Research, Frederick, MD 21702, USA.
authors: W
authors: W
authors: Shao
authors: HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA.
authors: S
authors: S
authors: Hill
authors: HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA.
authors: J
authors: J
authors: Spindler
authors: HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA.
authors: A L
authors: AL
authors: Ferris
authors: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors: J W
authors: JW
authors: Mellors
authors: HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA.
authors: M F
authors: MF
authors: Kearney
authors: Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111, USA.
authors: J M
authors: JM
authors: Coffin
authors: HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA. hughesst@mail.nih.gov.
authors: S H
authors: SH
authors: Hughes
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D002999:Clone Cells / Q000821:virology; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015894:Genome, Human; D006678:HIV / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000821:virology*; D006801:Humans; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D016662:Virus Integration / Q000235:genetics*; D017735:Virus Latency / Q000235:genetics*
chemical_list: D044966:Anti-Retroviral Agents; C491123:BACH2 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D004279:DNA, Viral; C478036:MRTFB protein, human; D012367:RNA, Viral; D014157:Transcription Factors