Progressive contraction of the latent HIV reservoir around a core of less-differentiated CD4+ memory T Cells

被引:110
作者
Jaafoura, S. [1 ]
de Herve, M. G. de Goer [1 ]
Hernandez-Vargas, E. A. [2 ]
Hendel-Chavez, H. [1 ]
Abdoh, M. [1 ]
Mateo, M. C. [1 ]
Krzysiek, R. [3 ,4 ]
Merad, M. [5 ]
Seng, R. [6 ]
Tardieu, M. [1 ,4 ]
Delfraissy, J. F. [1 ,4 ,7 ]
Goujard, C. [4 ,5 ,7 ]
Taoufik, Y. [1 ,4 ]
机构
[1] INSERM, U1012, F-94276 Le Kremlin Bicetre, France
[2] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany
[3] INSERM, U996, F-92140 Clamart, France
[4] Univ Paris 11, Fac Med, F-94276 Le Kremlin Bicetre, France
[5] Inst Gustave Roussy, Dept Med, F-94805 Villejuif, France
[6] INSERM, U1018, F-94275 Le Kremlin Bicetre, France
[7] Hop Univ Paris Sud, Dept Internal Med, F-94275 Le Kremlin Bicetre, France
关键词
ACTIVE ANTIRETROVIRAL THERAPY; PERSISTENCE; INFECTION; DNA; OPTIMIZATION; REPLICATION; INTEGRATION;
D O I
10.1038/ncomms6407
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
In patients who are receiving prolonged antiretroviral treatment (ART), HIV can persist within a small pool of long-lived resting memory CD4(+) T cells infected with integrated latent virus. This latent reservoir involves distinct memory subsets. Here we provide results that suggest a progressive reduction of the size of the blood latent reservoir around a core of less-differentiated memory subsets (central memory and stem cell-like memory (T-SCM) CD4(+) T cells). This process appears to be driven by the differences in initial sizes and decay rates between latently infected memory subsets. Our results also suggest an extreme stability of the T-SCM sub-reservoir, the size of which is directly related to cumulative plasma virus exposure before the onset of ART, stressing the importance of early initiation of effective ART. The presence of these intrinsic dynamics within the latent reservoir may have implications for the design of optimal HIV therapeutic purging strategies.
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页数:8
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