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Number of HIV-1 founder variants is determined by the recency of the source partner infection
Science ( IF 56.9 ) Pub Date : 2020-07-02 , DOI: 10.1126/science.aba5443
Ch Julián Villabona-Arenas 1, 2 , Matthew Hall 3 , Katrina A Lythgoe 3 , Stephen G Gaffney 4 , Roland R Regoes 5 , Stéphane Hué 1, 2 , Katherine E Atkins 1, 2, 6
Affiliation  

Sourcing HIV-1 infection HIV-1 has a multitude of strain variants, but sexual transmission of HIV-1 is assumed to result from productive infection by only one virus particle. Knowing the genetics of the virus strains that are transmitted could be crucial for developing successful vaccine strategies. Using epidemiological and genetic data from 112 pairs of sexual partners, Villabona-Arenas et al. found that individuals with acute infections are more likely to transmit multiple founder virus strains. In a phylodynamic approach that integrated phylogenetic analysis of sequence data with simulation of a transmission chain, the authors showed that multiple variant transmission is doubled during the first 3 months of infection irrespective of whether transmission was heterosexual or by men who have sex with men. Science, this issue p. 103 Acquiring infection from someone in the early stage of infection increases the risk of multiple–founder variant transmission. During sexual transmission, the high genetic diversity of HIV-1 within an individual is frequently reduced to one founder variant that initiates infection. Understanding the drivers of this bottleneck is crucial to developing effective infection control strategies. Little is known about the importance of the source partner during this bottleneck. To test the hypothesis that the source partner affects the number of HIV founder variants, we developed a phylodynamic model calibrated using genetic and epidemiological data on all existing transmission pairs for whom the direction of transmission and the infection stage of the source partner are known. Our results suggest that acquiring infection from someone in the acute (early) stage of infection increases the risk of multiple–founder variant transmission compared with acquiring infection from someone in the chronic (later) stage of infection. This study provides the first direct test of source partner characteristics to explain the low frequency of multiple–founder strain infections.

中文翻译:

HIV-1 创始人变体的数量取决于源伴侣感染的新近程度

寻找 HIV-1 感染 HIV-1 有多种毒株变种,但假定 HIV-1 的性传播仅由一种病毒颗粒产生感染所致。了解传播的病毒株的遗传学对于开发成功的疫苗策略至关重要。使用来自 112 对性伴侣的流行病学和遗传数据,Villabona-Arenas 等人。发现患有急性感染的个体更有可能传播多种创始病毒株。在将序列数据的系统发育分析与传播链模拟相结合的系统动力学方法中,作者表明,在感染的前 3 个月内,多变体传播加倍,无论传播是异性恋还是男男性行为者。科学,这个问题 p。103 在感染的早期从某人那里获得感染会增加多重创始人变异传播的风险。在性传播过程中,个体内 HIV-1 的高遗传多样性经常减少为一种引发感染的始祖变异。了解这一瓶颈的驱动因素对于制定有效的感染控制策略至关重要。在此瓶颈期间,源合作伙伴的重要性知之甚少。为了检验源合作伙伴影响 HIV 创始人变体数量的假设,我们开发了一个系统动力学模型,该模型使用所有现有传播对的遗传和流行病学数据进行校准,这些传播对的传播方向和源合作伙伴的感染阶段是已知的。我们的结果表明,与从感染的慢性(晚期)阶段的人那里获得感染相比,从感染的急性(早期)阶段的人那里获得感染会增加多始祖变异传播的风险。本研究首次对来源伙伴特征进行了直接测试,以解释多源菌株感染的低频率。
更新日期:2020-07-02
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