Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection

被引：546

作者：

Wagner, Thor A. ^{[1
,2
]}

McLaughlin, Sherry ^{[1
,2
]}

Garg, Kavita ^{[3
]}

Cheung, Charles Y. K. ^{[3
]}

Larsen, Brendan B. ^{[2
]}

Styrchak, Sheila ^{[1
]}

Huang, Hannah C. ^{[1
]}

Edlefsen, Paul T. ^{[2
,3
]}

Mullins, James I. ^{[2
]}

Frenkel, Lisa M. ^{[1
,2
]}

机构：

[1] Seattle Childrens Res Inst, Seattle, WA 98101 USA

[2] Univ Washington, Seattle, WA 98195 USA

[3] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

来源：

SCIENCE | 2014年 / 345卷 / 6196期

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; GENOME-WIDE ANALYSIS; ANTIRETROVIRAL THERAPY; LATENT RESERVOIR; T-CELLS; REPLICATION; EXPRESSION; MUTATIONS; LANDSCAPE; SELECTION;

D O I：

10.1126/science.1256304

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：

Antiretroviral treatment (ART) of HIV infection suppresses viral replication. Yet if ART is stopped, virus reemerges because of the persistence of infected cells. We evaluated the contribution of infected-cell proliferation and sites of proviral integration to HIV persistence. A total of 534 HIV integration sites (IS) and 63 adjacent HIV env sequences were derived from three study participants over 11.3 to 12.7 years of ART. Each participant had identical viral sequences integrated at the same position in multiple cells, demonstrating infected-cell proliferation. Integrations were overrepresented in genes associated with cancer and favored in 12 genes across multiple participants. Over time on ART, a greater proportion of persisting proviruses were in proliferating cells. HIV integration into specific genes may promote proliferation of HIV-infected cells, slowing viral decay during ART.

引用

页码：570 / 573

页数：4

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