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使用连续序列对 HIV 潜伏谱系年龄进行贝叶斯系统发育推断。

Bayesian phylogenetic inference of HIV latent lineage ages using serial sequences.

机构信息

Department of Evolution and Ecology, University of California, Davis, CA, USA.

出版信息

J R Soc Interface. 2023 Apr;20(201):20230022. doi: 10.1098/rsif.2023.0022. Epub 2023 Apr 19.

Abstract

HIV evolves rapidly within individuals, allowing phylogenetic studies to infer histories of viral lineages on short time scales. Latent HIV sequences are an exception to this rapid evolution, as their transcriptional inactivity leads to negligible mutation rates compared with non-latent HIV lineages. This difference in mutation rates generates potential information about the times at which sequences entered the latent reservoir, providing insight into the dynamics of the latent reservoir. A Bayesian phylogenetic method is developed to infer integration times of latent HIV sequences. The method uses informative priors to incorporate biologically sensible bounds on inferences (such as requiring sequences to become latent before being sampled) that many existing methods lack. A new simulation method is also developed, based on widely used epidemiological models of within-host viral dynamics, and applied to evaluate the new method-showing that point estimates and credible intervals are often more accurate than existing methods. Accurate estimates of latent integration dates are crucial in relating integration times to key events during HIV infection, such as treatment initiation. The method is applied to publicly available sequence data from four HIV patients, providing new insights regarding the temporal pattern of latent integration.

摘要

HIV 在个体内部迅速进化,这使得系统发育研究能够在短时间尺度上推断病毒谱系的历史。潜伏 HIV 序列是这种快速进化的一个例外,因为它们的转录不活跃导致与非潜伏 HIV 谱系相比,突变率可以忽略不计。这种突变率的差异产生了有关序列进入潜伏库时间的潜在信息,为了解潜伏库的动态提供了线索。开发了一种贝叶斯系统发育方法来推断潜伏 HIV 序列的整合时间。该方法使用信息先验来纳入对推断的合理生物学限制(例如,要求序列在被采样之前成为潜伏状态),而许多现有方法缺乏这些限制。还开发了一种新的模拟方法,该方法基于宿主内病毒动力学的广泛使用的流行病学模型,并应用于评估新方法——表明点估计和置信区间通常比现有方法更准确。准确估计潜伏整合日期对于将整合时间与 HIV 感染期间的关键事件(如治疗开始)联系起来至关重要。该方法应用于来自四名 HIV 患者的公开可用序列数据,为潜伏整合的时间模式提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6728/10113814/522d0c8db881/rsif20230022f01.jpg

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