Kostaki Evangelia-Georgia, Flampouris Andreas, Karamitros Timokratis, Chueca Natalia, Alvarez Marta, Casas Paz, Alejos Belen, Hatzakis Angelos, Garcia Federico, Paraskevis Dimitrios
Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Zoology, University of Oxford, Oxford, United Kingdom.
Front Microbiol. 2019 Mar 11;10:370. doi: 10.3389/fmicb.2019.00370. eCollection 2019.
The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41-6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain. We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000-2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences ( = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively. The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from ( < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2-79 sequences. The CRF02_AG regional dispersal differed across Spain ( = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) ( = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (t) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999-2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin. CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics.
循环重组形式02_AG（CRF02_AG）是1型人类免疫缺陷病毒（HIV-1）非B亚型中的主要进化枝，在西班牙的流行率为5.97%（95%置信区间-CI：5.41-6.57%）。我们的目的是估计CRF02_AG的区域聚集水平以及西班牙最大的CRF02_AG子流行的时空特征。我们研究了2000年至2014年期间从西班牙10个自治区的HIV-1确诊患者中获得的396条CRF02_AG序列。对391条CRF02_AG序列以及所有全球采样的CRF02_AG序列（=3302条）作为参考进行了系统发育分析。分别通过BEAST v1.8.0中的贝叶斯方法对最大的CRF02_AG单系簇进行了系统动力学和系统地理学分析，并使用Mesquite v3.4中的简约标准重建祖先状态。我们采样的西班牙自治区中HIV-1 CRF02_AG的流行率存在差异（<0.001）。系统发育分析显示，52.7%的CRF02_AG序列形成了56个单系簇，序列数量范围为2至79条。如单系聚类所示，CRF02_AG在西班牙的区域传播存在差异（=0.003）。对于最大的单系簇（子流行）（=79），49.4%的聚类序列来自马德里，而大多数序列（51.9%）是从男男性行为者（MSM）中获得的。分子钟分析表明，CRF02_AG子流行的起源（t）为2002年（中位数估计；95%最高后验密度-HPD区间：1999-2004）。此外，我们发现根据种族起源，CRF02_AG子流行内部存在显著聚类。CRF02_AG是在西班牙多次引入后出现的，在一些情况下随后进行了区域传播。我们表明，CRF02_AG传播在西班牙主要是由于区域传播。西班牙最大的CRF02_AG区域子流行的热点地区在马德里，与MSM传播风险群体相关。子流行的存在表明从马德里向其他地区发生了几次溢出。来自西班牙裔的CRF02_AG序列聚集在一个单独的亚分支中，表明本地和西班牙裔子流行之间没有联系。
