Multiple Origins of Virus Persistence during Natural Control of HIV Infection

被引：142

作者：

Boritz, Eli A. ^{[1
]}

Darko, Samuel ^{[1
]}

Swaszek, Luke ^{[1
]}

Wolf, Gideon ^{[1
]}

Wells, David ^{[2
]}

Wu, Xiaolin ^{[2
]}

Henry, Amy R. ^{[1
]}

Laboune, Farida ^{[1
]}

Hu, Jianfei ^{[1
]}

Ambrozak, David ^{[3
]}

Hughes, Marybeth S. ^{[4
]}

Hoh, Rebecca ^{[5
]}

Casazza, Joseph P. ^{[3
]}

Vostal, Alexander

Bunis, Daniel ^{[1
]}

Nganou-Makamdop, Krystelle ^{[1
]}

Lee, James S. ^{[1
]}

Migueles, Stephen A. ^{[6
]}

Koup, Richard A. ^{[3
]}

Connors, Mark ^{[6
]}

Moir, Susan ^{[6
]}

Schacker, Timothy ^{[8
]}

Maldarelli, Frank ^{[7
]}

Hughes, Stephen H. ^{[7
]}

Deeks, Steven G. ^{[5
]}

Douek, Daniel C. ^{[1
]}

机构：

[1] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[2] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA

[3] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[4] NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA

[5] Univ Calif San Francisco, Dept Med, San Francisco, CA 94110 USA

[6] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA

[7] NCI, HIV Dynam & Replicat Program, NIH, Frederick, MD 21702 USA

[8] Univ Minnesota, Dept Med, Program HIV Med, Minneapolis, MN 55455 USA

来源：

CELL | 2016年 / 166卷 / 04期

关键词：

ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; ELITE SUPPRESSORS; LATENT RESERVOIR; IN-VIVO; REPLICATION; PROLIFERATION; TYPE-1; LYMPHOCYTES; ACTIVATION;

D O I：

10.1016/j.cell.2016.06.039

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：

Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites, and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (T-FH) cells and non-T-FH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity.

引用

页码：1004 / 1015

页数：12

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