Phenotypic analysis of the unstimulated in vivo HIV CD4 T cell reservoir

被引：58

作者：

Neidleman, Jason ^{[1
,2
]}

Luo, Xiaoyu ^{[1
]}

Frouard, Julie ^{[1
,2
]}

Xie, Guorui ^{[1
,2
]}

Hsiao, Feng ^{[1
,2
]}

Ma, Tongcui ^{[1
,2
]}

Morcilla, Vincent ^{[3
]}

Lee, Ashley ^{[3
]}

Telwatte, Sushama ^{[4
,5
]}

Thomas, Reuben ^{[1
]}

Tamaki, Whitney ^{[6
]}

Wheeler, Benjamin ^{[6
]}

Hoh, Rebecca ^{[7
]}

Somsouk, Ma ^{[5
,8
]}

Vohra, Poonam ^{[9
]}

Milush, Jeffrey ^{[6
]}

James, Katherine Sholtis ^{[10
]}

Archin, Nancie M. ^{[10
]}

Hunt, Peter W. ^{[11
]}

Deeks, Steven G. ^{[7
]}

Yukl, Steven A. ^{[4
,5
]}

Palmer, Sarah ^{[3
]}

Greene, Warner C. ^{[1
,6
]}

Roan, Nadia R. ^{[1
,2
]}

机构：

[1] Gladstone Inst, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA

[3] Univ Sydney, Ctr Virus Res, Westmead Inst Med Res, Sydney, NSW, Australia

[4] San Francisco Vet Affairs VA Med Ctr, San Francisco, CA USA

[5] Univ Calif San Francisco, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[7] Univ Calif San Francisco, Div HIV Infect Dis & Global Med, San Francisco, CA 94143 USA

[8] San Francisco Gen Hosp, Dept Med, Div Gastroenterol, San Francisco, CA 94110 USA

[9] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA

[10] Univ N Carolina, Div Infect Dis, Sch Med, Chapel Hill, NC 27515 USA

[11] Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94143 USA

来源：

ELIFE | 2020年 / 9卷

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

REPLICATION-COMPETENT HIV-1; LATENT RESERVOIR; ANTIRETROVIRAL THERAPY; PROVIRUSES PRODUCE; INTACT HIV-1; PERSISTENCE; CYTOMETRY; QUANTIFICATION; IDENTIFICATION; PROLIFERATION;

D O I：

10.7554/eLife.60933

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The latent reservoir is a major barrier to HIV cure. As latently infected cells cannot be phenotyped directly, the features of the in vivo reservoir have remained elusive. Here, we describe a method that leverages high-dimensional phenotyping using CyTOF to trace latently infected cells reactivated ex vivo to their original pre-activation states. Our results suggest that, contrary to common assumptions, the reservoir is not randomly distributed among cell subsets, and is remarkably conserved between individuals. However, reservoir composition differs between tissues and blood, as do cells successfully reactivated by different latency reversing agents. By selecting 8-10 of our 39 original CyTOF markers, we were able to isolate highly purified populations of unstimulated in vivo latent cells. These purified populations were highly enriched for replication-competent and intact provirus, transcribed HIV, and displayed clonal expansion. The ability to isolate unstimulated latent cells from infected individuals enables previously impossible studies on HIV persistence.

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