Establishment and stability of the latent HIV-1 DNA reservoir
Establishment and stability of the latent HIV-1 DNA reservoir
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DOI：
10.7554/elife.18889
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发表时间：
2016-11-15
期刊：
影响因子：
7.7
通讯作者：
Albert, Jan
中科院分区：
文献类型：
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作者：
Brodin, Johanna;Zanini, Fabio;Albert, Jan
HIV-1感染无法治愈，因为尽管多年的抑制性抗逆转录病毒治疗（ART），病毒仍作为整合的前病毒DNA存在于长寿细胞中。在之前的一篇论文（Zanini等人，2015）中，我们记录了10名未经治疗的患者的HIV-1演变。在此，我们描述了相同患者在3 - 18年的抑制性ART治疗后病毒DNA储库的建立、周转和演变。由于G至A超突变，平均14%（范围0 - 42%）的DNA序列存在缺陷。剩余的DNA序列显示，没有证据表明多年的抑制性ART的演变。大多数序列的DNA水库是非常相似的病毒在血浆中活跃复制（RNA序列）开始前不久的ART。结果不支持持续的HIV-1复制作为一种机制，以维持HIV-1水库在抑制治疗。相反，数据表明，只要患者未经治疗，DNA变异就会发生逆转，而抑制性ART会阻止这种逆转。
HIV-1 infection cannot be cured because the virus persists as integrated proviral DNA in long-lived cells despite years of suppressive antiretroviral therapy (ART). In a previous paper (Zanini et al, 2015) we documented HIV-1 evolution in 10 untreated patients. Here we characterize establishment, turnover, and evolution of viral DNA reservoirs in the same patients after 3-18 years of suppressive ART. A median of 14% (range 0-42%) of the DNA sequences were defective due to G-to-A hypermutation. Remaining DNA sequences showed no evidence of evolution over years of suppressive ART. Most sequences from the DNA reservoirs were very similar to viruses actively replicating in plasma (RNA sequences) shortly before start of ART. The results do not support persistent HIV-1 replication as a mechanism to maintain the HIV-1 reservoir during suppressive therapy. Rather, the data indicate that DNA variants are turning over as long as patients are untreated and that suppressive ART halts this turnover.