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Phylogenetic analysis consistent with a clinical history of sexual transmission of HIV-1 from a single donor reveals transmission of highly distinct variants.

机译:系统发育分析与来自单个供体的HIV-1的性传播的临床历史一致,揭示了高度不同的变体的传播。

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摘要

BACKGROUND: To combat the pandemic of human immunodeficiency virus 1 (HIV-1), a successful vaccine will need to cope with the variability of transmissible viruses. Human hosts infected with HIV-1 potentially harbour many viral variants but very little is known about viruses that are likely to be transmitted, or even if there are viral characteristics that predict enhanced transmission in vivo. We show for the first time that genetic divergence consistent with a single transmission event in vivo can represent several years of pre-transmission evolution. RESULTS: We describe a highly unusual case consistent with a single donor transmitting highly related but distinct HIV-1 variants to two individuals on the same evening. We confirm that the clustering of viral genetic sequences, present within each recipient, is consistent with the history of a single donor across the viral env, gag and pol genes by maximum likelihood and bayesian Markov Chain Monte Carlo based phylogenetic analyses. Based on an uncorrelated, lognormal relaxed clock of env gene evolution calibrated with other datasets, the time since the most recent common ancestor is estimated as 2.86 years prior to transmission (95% confidence interval 1.28 to 4.54 years). CONCLUSION: Our results show that an effective design for a preventative vaccine will need to anticipate extensive HIV-1 diversity within an individual donor as well as diversity at the population level.
机译:背景:为了抵抗人类免疫缺陷病毒1(HIV-1)的大流行,成功的疫苗将需要应对可传播病毒的变异性。感染了HIV-1的人类宿主可能会携带许多病毒变异体,但对于可能传播的病毒,甚至某些病毒特征可以预测体内传播的增强,人们所知甚少。我们首次显示与体内单个传播事件一致的遗传差异可以代表几年的传播前进化。结果:我们描述了一个非常不寻常的情况,与单个捐赠者在同一晚向两个个体传播高度相关但截然不同的HIV-1变异相一致。我们通过最大可能性和基于贝叶斯马尔可夫链蒙特卡洛的系统发育分析,确认存在于每个受体内的病毒遗传序列的聚类与跨病毒env,gag和pol基因的单个供体的历史是一致的。根据使用其他数据集校准的env基因进化的不相关,对数正态松弛时钟,估计自最近的共同祖先以来的时间为传播前2.86年(95%置信区间1.28至4.54年)。结论:我们的结果表明,预防性疫苗的有效设计将需要预测单个供体中广泛的HIV-1多样性以及人群水平的多样性。

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