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

被引：648

作者：

Maldarelli, F. ^{[1
]}

Wu, X. ^{[2
]}

Su, L. ^{[2
]}

Simonetti, F. R. ^{[1
,3
]}

Shao, W. ^{[2
]}

Hill, S. ^{[1
]}

Spindler, J. ^{[1
]}

Ferris, A. L. ^{[1
]}

Mellors, J. W. ^{[4
]}

Kearney, M. F. ^{[1
]}

Coffin, J. M. ^{[5
]}

Hughes, S. H. ^{[1
]}

机构：

[1] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA

[2] Leidos Biomed Res, Frederick, MD 21702 USA

[3] Univ Milan, Dept Biomed & Clin Sci L Sacco, I-20122 Milan, Italy

[4] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA

[5] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA

来源：

SCIENCE | 2014年 / 345卷 / 6193期

关键词：

CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; RESERVOIR; GENES; CURE; IDENTIFICATION; LYMPHOMAS; DYNAMICS; DNA;

D O I：

10.1126/science.1254194

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：179 / 183

页数：5

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