Publication Date:
2014-06-28
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262401/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262401/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maldarelli, F -- Wu, X -- Su, L -- Simonetti, F R -- Shao, W -- Hill, S -- Spindler, J -- Ferris, A L -- Mellors, J W -- Kearney, M F -- Coffin, J M -- Hughes, S H -- 25XS119/PHS HHS/ -- HSSN261200800001E/PHS HHS/ -- R01 CA089441/CA/NCI NIH HHS/ -- R37 CA089441/CA/NCI NIH HHS/ -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Jul 11;345(6193):179-83. doi: 10.1126/science.1254194. Epub 2014 Jun 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA. ; Leidos Biomedical Research, Frederick, MD 21702, USA. ; 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. ; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. ; Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111, USA. ; HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA. hughesst@mail.nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24968937" target="_blank"〉PubMed〈/a〉
Keywords:
Anti-Retroviral Agents/therapeutic use
;
Basic-Leucine Zipper Transcription Factors/*genetics
;
Clone Cells/virology
;
DNA, Viral/analysis/genetics/metabolism
;
Genome, Human
;
HIV/genetics/*physiology
;
HIV Infections/drug therapy/genetics/*virology
;
Humans
;
RNA, Viral/analysis/genetics/metabolism
;
Transcription Factors/*genetics
;
Virus Integration/*genetics
;
Virus Latency/*genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
