State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University, Shenyang, China.
National Health Commission (NHC) Key Laboratory of AIDS Prevention and Treatment, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University, Shenyang, China.
Front Cell Infect Microbiol. 2024 May 22;14:1388059. doi: 10.3389/fcimb.2024.1388059. eCollection 2024.
HIV molecular network based on genetic distance (GD) has been extensively utilized. However, the GD threshold for the non-B subtype differs from that of subtype B. This study aimed to optimize the GD threshold for inferring the CRF01_AE molecular network.
Next-generation sequencing data of partial CRF01_AE sequences were obtained for 59 samples from 12 transmission pairs enrolled from a high-risk cohort during 2009 and 2014. The paired GD was calculated using the Tamura-Nei 93 model to infer a GD threshold range for HIV molecular networks.
2,019 CRF01_AE pol sequences and information on recent HIV infection (RHI) from newly diagnosed individuals in Shenyang from 2016 to 2019 were collected to construct molecular networks to assess the ability of the inferred GD thresholds to predict recent transmission events. When HIV transmission occurs within a span of 1-4 years, the mean paired GD between the sequences of the donor and recipient within the same transmission pair were as follow: 0.008, 0.011, 0.013, and 0.023 substitutions/site. Using these four GD thresholds, it was found that 98.9%, 96.0%, 88.2%, and 40.4% of all randomly paired GD values from 12 transmission pairs were correctly identified as originating from the same transmission pairs. In the real world, as the GD threshold increased from 0.001 to 0.02 substitutions/site, the proportion of RHI within the molecular network gradually increased from 16.6% to 92.3%. Meanwhile, the proportion of links with RHI gradually decreased from 87.0% to 48.2%. The two curves intersected at a GD of 0.008 substitutions/site.
A suitable range of GD thresholds, 0.008-0.013 substitutions/site, was identified to infer the CRF01_AE molecular transmission network and identify HIV transmission events that occurred within the past three years. This finding provides valuable data for selecting an appropriate GD thresholds in constructing molecular networks for non-B subtypes.
基于遗传距离（GD）的 HIV 分子网络已被广泛应用。然而，非 B 亚型的 GD 阈值与 B 亚型不同。本研究旨在优化推断 CRF01_AE 分子网络的 GD 阈值。
从 2009 年至 2014 年期间，从一个高危人群中的 12 个传播对中招募的 59 个样本中获得了部分 CRF01_AE 序列的下一代测序数据。使用 Tamura-Nei 93 模型计算配对 GD，以推断 HIV 分子网络的 GD 阈值范围。
收集了 2016 年至 2019 年沈阳新诊断个体的 2019 个 CRF01_AE pol 序列和最近感染 HIV（RHI）的信息，以构建分子网络，评估推断的 GD 阈值预测最近传播事件的能力。当 HIV 传播发生在 1-4 年内时，同一传播对中供体和受体序列之间的平均配对 GD 分别为 0.008、0.011、0.013 和 0.023 个取代/位点。使用这四个 GD 阈值，发现 12 个传播对中所有随机配对 GD 值的 98.9%、96.0%、88.2%和 40.4%被正确识别为来自同一传播对。在现实世界中，随着 GD 阈值从 0.001 增加到 0.02 个取代/位点，分子网络中 RHI 的比例从 16.6%逐渐增加到 92.3%。同时，具有 RHI 的链接比例从 87.0%逐渐降低到 48.2%。这两条曲线在 GD 为 0.008 个取代/位点处相交。
确定了合适的 GD 阈值范围（0.008-0.013 个取代/位点），以推断 CRF01_AE 分子传播网络并识别过去三年内发生的 HIV 传播事件。这一发现为选择非 B 亚型构建分子网络的合适 GD 阈值提供了有价值的数据。
