Persistent HIV-1 replication maintains the tissue reservoir during therapy

被引：500

作者：

Lorenzo-Redondo, Ramon ^{[1
]}

Fryer, Helen R. ^{[2
]}

Bedford, Trevor ^{[3
]}

Kim, Eun-Young ^{[1
]}

Archer, John ^{[4
]}

Pond, Sergei L. Kosakovsky ^{[5
,13
]}

Chung, Yoon-Seok ^{[6
]}

Penugonda, Sudhir ^{[1
]}

Chipman, Jeffrey G. ^{[7
]}

Fletcher, Courtney V. ^{[8
]}

Schacker, Timothy W. ^{[9
]}

Malim, Michael H. ^{[10
]}

Rambaut, Andrew ^{[11
]}

Haase, Ashley T. ^{[12
]}

McLean, Angela R. . ^{[2
]}

Wolinsky, Steven M. ^{[1
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60011 USA

[2] Univ Oxford, Inst Emerging Infect, Dept Zool, Oxford OX1 3PS, England

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

[4] Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, P-4485661 Vairao, Portugal

[5] Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA

[6] Korea Natl Inst Hlth, Div Aids, Ctr Immunol & Pathol, Chungju Si 28159, Chungcheongbuk, South Korea

[7] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA

[8] Univ Nebraska Med Ctr, Coll Pharm, Antiviral Pharmacol Lab, Omaha, NE 68198 USA

[9] Univ Minnesota, Div Infect Dis, Minneapolis, MN 55455 USA

[10] Kings Coll London, Guys Hosp, Dept Infect Dis, London SE21 7DN, England

[11] Univ Edinburgh, Ctr Immunol Infect & Evolut, Edinburgh EH9 3FL, Midlothian, Scotland

[12] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA

[13] Temple Univ, Inst Genom & Evolutionary Med, Philadelphia, PA 19122 USA

来源：

NATURE | 2016年 / 530卷 / 7588期

基金：

美国国家卫生研究院; 英国医学研究理事会; 英国惠康基金; 欧洲研究理事会;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; IN-VIVO; PERIPHERAL-BLOOD; EVOLUTION; DNA; SEQUENCES; DYNAMICS; ACCURATE;

D O I：

10.1038/nature16933

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：

Lymphoid tissue is a key reservoir established by HIV-1 during acute infection. It is a site associated with viral production, storage of viral particles in immune complexes, and viral persistence. Although combinations of antiretroviral drugs usually suppress viral replication and reduce viral RNA to undetectable levels in blood, it is unclear whether treatment fully suppresses viral replication in lymphoid tissue reservoirs. Here we show that virus evolution and trafficking between tissue compartments continues in patients with undetectable levels of virus in their bloodstream. We present a spatial and dynamic model of persistent viral replication and spread that indicates why the development of drug resistance is not a foregone conclusion under conditions in which drug concentrations are insufficient to completely block virus replication. These data provide new insights into the evolutionary and infection dynamics of the virus population within the host, revealing that HIV-1 can continue to replicate and replenish the viral reservoir despite potent antiretroviral therapy.

引用

页码：51 / +

页数：20

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