IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART.
IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART.
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DOI：
10.1172/jci22574
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发表时间：
2005-01
期刊：
影响因子：
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通讯作者：
Feng-xiang Wang;Yan Xu;J. Sullivan;Emily Souder;E. Argyris;E. Acheampong;Jaime Fisher;María Sierra;M. Thomson;R. Nájera;I. Frank;J. Kulkosky;R. Pomerantz;G. Nunnari
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文献类型：
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作者：
Feng-xiang Wang;Yan Xu;J. Sullivan;Emily Souder;E. Argyris;E. Acheampong;Jaime Fisher;María Sierra;M. Thomson;R. Nájera;I. Frank;J. Kulkosky;R. Pomerantz;G. Nunnari
HIV-1在接受高效抗逆转录病毒治疗（HAART）的病毒抑制感染个体中的持续存在仍然是一个主要的治疗问题。细胞因子的使用已被设想为刺激这些个体中的潜伏前病毒的额外治疗策略。使用IL-2的免疫活化疗法已经显示出一些前景。在本研究中，我们发现IL-7在增强HIV-1前病毒再激活方面比单独IL-2或IL-2与植物血凝素（PHA）联合应用更有效。IL-7也显示出诱导来自抑制性HAART的HIV-1感染患者的静息CD 4（+）T淋巴细胞的前病毒再激活的积极趋势。此外，从诱导的病毒的病毒包膜gp 120基因的系统发育分析表明，不同的前病毒准种已被激活的IL-7，与PHA/IL-2治疗激活。因此，这些研究表明，前病毒潜伏期的不同激活剂可能会扰乱和潜在地耗尽病毒抑制个体中前病毒档案的仅选定的特定部分。IL-7的已知免疫调节作用可以与其刺激HIV-1从静息CD 4（+）T淋巴细胞复制的能力相结合，以及其他部分，以潜在地耗尽HIV-1储库并导致免疫抗逆转录病毒方法的合理设计。
The persistence of HIV-1 in virally 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 virally 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.