HIV-1 Integration Landscape during Latent and Active Infection

被引：360

作者：

Cohn, Lillian B. ^{[1
]}

Silva, Israel T. ^{[1
,2
,3
]}

Oliveira, Thiago Y. ^{[1
]}

Rosales, Rafael A. ^{[4
]}

Parrish, Erica H. ^{[5
,6
]}

Learn, Gerald H. ^{[5
,6
]}

Hahn, Beatrice H. ^{[5
,6
]}

Czartoski, Julie L. ^{[7
]}

McElrath, M. Juliana ^{[7
]}

Lehmann, Clara ^{[8
,9
]}

Klein, Florian ^{[1
]}

Caskey, Marina ^{[1
]}

Walker, Bruce D. ^{[10
,11
]}

Siliciano, Janet D. ^{[12
]}

Siliciano, Robert F. ^{[11
,12
]}

Jankovic, Mila ^{[1
]}

Nussenzweig, Michel C. ^{[1
,11
]}

机构：

[1] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA

[2] Natl Inst Sci & Technol Stem Cell & Cell Therapy, BR-14051140 Ribeirao Preto, Brazil

[3] Ctr Cell Based Therapy, BR-14051140 Ribeirao Preto, Brazil

[4] Univ Sao Paulo, Dept Comp & Matemat, BR-14049901 Ribeirao Preto, Brazil

[5] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA

[6] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA

[7] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA

[8] Univ Hosp Cologne, Dept Internal Med 1, D-50924 Cologne, Germany

[9] German Ctr Infect Res, D-50924 Cologne, Germany

[10] Ragon Inst MGH, Cambridge, MA 02139 USA

[11] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[12] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

来源：

CELL | 2015年 / 160卷 / 03期

关键词：

CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; SEQUENCING REVEALS; SITES; PERSISTENCE; RESERVOIR; GENES; PROLIFERATION; VIRUS; IDENTIFICATION;

D O I：

10.1016/j.cell.2015.01.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The barrier to curing HIV-1 is thought to reside primarily in CD4(+) T cells containing silent proviruses. To characterize these latently infected cells, we studied the integration profile of HIV-1 in viremic progressors, individuals receiving antiretroviral therapy, and viremic controllers. Clonally expanded T cells represented the majority of all integrations and increased during therapy. However, none of the 75 expanded T cell clones assayed contained intact virus. In contrast, the cells bearing single integration events decreased in frequency over time on therapy, and the surviving cells were enriched for HIV-1 integration in silent regions of the genome. Finally, there was a strong preference for integration into, or in close proximity to, Alu repeats, which were also enriched in local hotspots for integration. The data indicate that dividing clonally expanded T cells contain defective proviruses and that the replication-competent reservoir is primarily found in CD4(+) T cells that remain relatively quiescent.

引用

页码：420 / 432

页数：13

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