Pérez-Parra Santiago, Chueca Natalia, Álvarez Marta, Pasquau Juan, Omar Mohamed, Collado Antonio, Vinuesa David, Lozano Ana Belen, Yebra Gonzalo, García Federico
Servicio de Microbiología Clínica, Hospital Universitario San Cecilio, Campus de la Salud e Instituto de Investigación IBS, Granada, Spain.
Servicio de Infecciosas, Hospital Virgen de las Nieves, Granada, Spain.
PLoS One. 2017 Oct 30;12(10):e0186928. doi: 10.1371/journal.pone.0186928. eCollection 2017.
Phylogenetic studies are a valuable tool to understand viral transmission patterns and the role of immigration in HIV-1 spread. We analyzed the spatio-temporal relationship of different HIV-1 non-B subtype variants over time using phylogenetic analysis techniques. We collected 693 pol (PR+RT) sequences that were sampled from 2005 to 2012 from naïve patients in different hospitals in southern Spain. We used REGA v3.0 to classify them into subtypes and recombinant forms, which were confirmed by phylogenetic analysis through maximum likelihood (ML) using RAxML. For the main HIV-1 non-B variants, publicly available, genetically similar sequences were sought using HIV-BLAST. The presence of HIV-1 lineages circulating in our study population was established using ML and Bayesian inference (BEAST v1.7.5) and transmission networks were identified. We detected 165 (23.4%) patients infected with HIV-1 non-B variants: 104 (63%) with recombinant viruses in pol: CRF02_AG (71, 43%), CRF14_BG (8, 4.8%), CRF06_cpx (5, 3%) and nine other recombinant forms (11, 6.7%) and unique recombinants (9, 5.5%). The rest (61, 37%) were infected with non-recombinant subtypes: A1 (30, 18.2%), C (7, [4.2%]), D (3, [1.8%]), F1 (9, 5.5%) and G (12, 7.3%). Most patients infected with HIV-1 non-B variants were men (63%, p < 0.001) aged over 35 (73.5%, p < 0.001), heterosexuals (92.2%, p < 0.001), from Africa (59.5%, p < 0.001) and living in the El Ejido area (62.4%, p<0.001). We found lineages of epidemiological relevance (mainly within Subtype A1), imported primarily through female sex workers from East Europe. We detected 11 transmission clusters of HIV-1 non-B Subtypes, which included patients born in Spain in half of them. We present the phylogenetic profiles of the HIV-1 non-B variants detected in southern Spain, and explore their putative geographical origins. Our data reveals a high HIV-1 genetic diversity likely due to the import of viral lineages that circulate in other countries. The highly immigrated El Ejido area acts as a gateway through which different subtypes are introduced into other regions, hence the importance of setting up epidemiological control measures to prevent future outbreaks.
系统发育研究是了解病毒传播模式以及移民在HIV-1传播中作用的宝贵工具。我们使用系统发育分析技术分析了不同HIV-1非B亚型变体随时间的时空关系。我们收集了2005年至2012年期间从西班牙南部不同医院的初治患者中采样的693条pol（蛋白酶+逆转录酶）序列。我们使用REGA v3.0将它们分类为亚型和重组形式，并通过使用RAxML的最大似然法（ML）进行系统发育分析来确认。对于主要的HIV-1非B变体，使用HIV-BLAST寻找公开可用的、基因相似的序列。使用ML和贝叶斯推断（BEAST v1.7.5）确定我们研究人群中循环的HIV-1谱系，并识别传播网络。我们检测到165名（23.4%）感染HIV-1非B变体的患者：104名（63%）在pol中有重组病毒：CRF02_AG（71名，43%）、CRF14_BG（8名，4.8%）、CRF06_cpx（5名，3%）和其他9种重组形式（11名，6.7%）以及独特重组体（9名，5.5%）。其余（61名，37%）感染的是非重组亚型：A1（30名，18.2%）、C（7名，[4.2%]）、D（3名，[1.8%]）、F1（9名，5.5%）和G（12名，7.3%）。大多数感染HIV-1非B变体的患者为男性（63%，p<0.001），年龄超过35岁（73.5%，p<0.001），异性恋者（92.2%，p<0.001），来自非洲（59.5%，p<0.001）且居住在埃尔埃希多地区（62.4%，p<0.001）。我们发现了具有流行病学相关性的谱系（主要在A1亚型内），主要通过来自东欧的女性性工作者传入。我们检测到11个HIV-1非B亚型的传播簇，其中一半包括在西班牙出生的患者。我们展示了在西班牙南部检测到的HIV-1非B变体的系统发育概况，并探索它们可能的地理起源。我们的数据显示，由于其他国家流行的病毒谱系的输入，HIV-1具有高度的遗传多样性。移民高度集中的埃尔埃希多地区充当了一个门户，不同亚型通过该门户被引入其他地区，因此建立流行病学控制措施以预防未来疫情爆发至关重要。
