IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART

被引:213
作者
Wang, FX
Xu, Y
Sullivan, J
Souder, E
Argyris, EG
Acheampong, EA
Fisher, J
Sierra, M
Thomson, MM
Najera, R
Frank, I
Kulkosky, J
Pomerantz, RJ
Nunnari, G
机构
[1] Thomas Jefferson Univ, Dept Med, Div Infect Dis & Environm Med, Ctr Human Virol & Biodef, Philadelphia, PA 19107 USA
[2] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA
[3] Inst Salud Carlos III, Ctr Nacl Microbiol, Area Patogenia Viral, Madrid, Spain
关键词
D O I
10.1172/JCI200522574
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The persistence of HIV-1 in vitally suppressed infected individuals on highly active antiretroviral therapy (HAART) remains a major therapeutic problem. The use of cytokines has been envisioned as an additional therapeutic strategy to stimulate latent proviruses in these individuals. Immune activation therapy using IL-2 has shown some promise. In the present study, we found that IL-7 was significantly more effective at enhancing HIV-1 proviral reactivation than either IL-2 alone or IL-2 combined with phytohemagglutinin (PHA) in CD8-depleted PBMCs. IL-7 also showed a positive trend for inducing proviral reactivation from resting CD4(+) T lymphocytes from HIV-1-infected patients on suppressive HAART. Moreover, the phylogenetic analyses of viral envelope gp120 genes from induced viruses indicated that distinct proviral quasispecies had been activated by IL-7, as compared with those activated by the PHA/IL-2 treatment. These studies thus demonstrate that different activators of proviral latency may perturb and potentially deplete only selected, specific portions of the proviral archive in vitally suppressed individuals. The known immunomodulatory effects of IL-7 could be combined with its ability to stimulate HIV-1 replication from resting CD4(+) T lymphocytes, in addition to other moieties, to potentially deplete HIV-1 reservoirs and lead to the rational design of immune-antiretroviral approaches.
引用
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页码:128 / 137
页数:10
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