Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Department of Environmental Systems Science, ETH Zurich, Zurich, Switzerland.
Nat Commun. 2020 Nov 2;11(1):5542. doi: 10.1038/s41467-020-19198-7.
The HIV-1 reservoir is the major hurdle to curing HIV-1. However, the impact of the viral genome on the HIV-1 reservoir, i.e. its heritability, remains unknown. We investigate the heritability of the HIV-1 reservoir size and its long-term decay by analyzing the distribution of those traits on viral phylogenies from both partial-pol and viral near full-length genome sequences. We use a unique nationwide cohort of 610 well-characterized HIV-1 subtype-B infected individuals on suppressive ART for a median of 5.4 years. We find that a moderate but significant fraction of the HIV-1 reservoir size 1.5 years after the initiation of ART is explained by genetic factors. At the same time, we find more tentative evidence for the heritability of the long-term HIV-1 reservoir decay. Our findings indicate that viral genetic factors contribute to the HIV-1 reservoir size and hence the infecting HIV-1 strain may affect individual patients' hurdle towards a cure.
HIV-1 储存库是治愈 HIV-1 的主要障碍。然而，病毒基因组对 HIV-1 储存库的影响，即其遗传性，尚不清楚。我们通过分析来自部分 pol 和病毒全长基因组序列的病毒系统发育树上这些特征的分布，来研究 HIV-1 储存库大小及其长期衰减的遗传性。我们使用了一个独特的全国性队列，该队列由 610 名经过充分特征描述的 HIV-1 亚型 B 感染个体组成，这些个体在接受抑制性 ART 治疗的中位数为 5.4 年。我们发现，在开始 ART 后 1.5 年，HIV-1 储存库大小的一个中等但显著的部分可以用遗传因素来解释。同时，我们发现了长期 HIV-1 储存库衰减的遗传性的更初步证据。我们的研究结果表明，病毒遗传因素有助于 HIV-1 储存库的大小，因此，感染 HIV-1 的毒株可能会影响个体患者治愈的障碍。
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