Department of Medicine, University of Cambridge, Cambridge, UK.
Yong Loo Lin School of Medicine, Singapore, Singapore.
Sci Rep. 2018 Feb 8;8(1):2639. doi: 10.1038/s41598-018-20682-w.
The persistence of infected T cells harbouring intact HIV proviruses is the barrier to the eradication of HIV. This reservoir is stable over long periods of time despite antiretroviral therapy. There has been controversy on whether low level viral replication is occurring at sanctuary sites periodically reseeding infected cells into the latent reservoir to account its durability. To study viral evolution in a physiologically relevant population of latent viruses, we repeatedly performed virus outgrowth assays on a stably treated HIV positive patient over two years and sequenced the reactivated latent viruses. We sought evidence of increasing sequence pairwise distances with time as evidence of ongoing viral replication. 64 reactivatable latent viral sequences were obtained over 103 weeks. We did not observe an increase in genetic distance of the sequences with the time elapsed between sampling. No evolution could be discerned in these reactivatable latent viruses. Thus, in this patient, the contribution of low-level replication to the maintenance of the latent reservoir detectable in the blood compartment is limited.
受感染的 T 细胞中含有完整 HIV 前病毒的持续存在是 HIV 根除的障碍。尽管进行了抗逆转录病毒治疗，但该储库在很长一段时间内都是稳定的。关于隐匿部位是否会定期发生低水平病毒复制，从而将感染细胞重新播种到潜伏储库中以解释其持久性，一直存在争议。为了在生理相关的潜伏病毒群体中研究病毒进化，我们在两年的时间里反复对一名稳定接受治疗的 HIV 阳性患者进行病毒扩增测定，并对重新激活的潜伏病毒进行测序。我们寻求随着时间的推移序列对之间距离增加的证据，以证明持续存在病毒复制。在 103 周的时间内获得了 64 个可重新激活的潜伏病毒序列。我们没有观察到在两次采样之间时间流逝时序列遗传距离的增加。在这些可重新激活的潜伏病毒中没有发现进化。因此，在这名患者中，血液中可检测到的低水平复制对潜伏储库的维持作用有限。
