Interleukin-7 promotes HIV persistence during antiretroviral therapy
Interleukin-7 promotes HIV persistence during antiretroviral therapy
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DOI：
10.1182/blood-2012-11-465625
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发表时间：
2013-05-23
期刊：
影响因子：
20.3
通讯作者：
Chomont, Nicolas
中科院分区：
文献类型：
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作者：
Vandergeeten, Claire;Fromentin, Remi;Chomont, Nicolas
在抗逆转录病毒治疗（ART）期间，HIV在潜伏感染的记忆性CD 4（+）T细胞中持续存在。当给予接受抑制性ART的HIV感染受试者时，白细胞介素-7（IL-7）通过促进其存活和增殖来增加CD 4（+）T细胞的数量。然而，很少有人知道IL-7对艾滋病病毒的持续性在ART的影响。通过分离大量的CD 4（+）T细胞从艾滋病病毒感染的受试者，我们证明，IL-7增强病毒生产的生产性感染的细胞，但不破坏潜伏感染的细胞中的病毒潜伏期。当给予病毒抑制受试者时，IL-7导致记忆性CD 4（+）T细胞快速增殖，导致治疗后4周携带整合HIV DNA的循环CD 4（+）T细胞绝对数量增加70%。在大多数研究受试者中，病毒储库的遗传多样性在恢复至基线值之前短暂增加。总之，我们的研究结果表明，IL-7促进艾滋病毒的持久性机制，在ART通过提高残留水平的病毒生产和诱导潜伏感染细胞的增殖，并表明IL-7并不代表一个合适的候选治疗策略，艾滋病毒根除。该试验在www.clinicaltrials.gov上注册为#NCT 00099671（AIDS临床试验组方案5214）。
HIV persists in latently infected memory CD4(+) T cells during antiretroviral therapy (ART). When administered to HIV-infected subjects receiving suppressive ART, interleukin-7 (IL-7) increases the number of CD4(+) T cells by promoting their survival and proliferation. However, little is known about the impact of IL-7 on HIV persistence during ART. By isolating large numbers of CD4(+) T cells from HIV-infected subjects, we demonstrate that IL-7 enhances viral production in productively infected cells but does not disrupt viral latency in latently infected cells. When administered to virally suppressed subjects, IL-7 led to the rapid proliferation of memory CD4(+) T cells, which resulted in a 70% increase in the absolute number of circulating CD4(+) T cells harboring integrated HIV DNA 4 weeks after therapy. The genetic diversity of the viral reservoir increased transiently in the majority of the subjects studied before returning to baseline values. Altogether, our results indicate that IL-7 promotes the mechanisms of HIV persistence during ART by enhancing residual levels of viral production and inducing proliferation of latently infected cells, and suggest that IL-7 does not represent a suitable candidate therapeutic strategy for HIV eradication. This trial was registered at www.clinicaltrials.gov as #NCT00099671 (AIDS Clinical Trials Group protocol 5214).