Hill Gracelyn, Pérez-Losada Marcos, Delgado Elena, Benito Sonia, Montero Vanessa, Gil Horacio, Sánchez Mónica, Cañada-García Javier E, García-Bodas Elena, Crandall Keith A, Thomson Michael M
Computational Biology Institute, George Washington University, Washington, DC, United States.
Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, DC, United States.
Front Microbiol. 2022 May 16;13:863123. doi: 10.3389/fmicb.2022.863123. eCollection 2022.
CRF47_BF is a circulating recombinant form (CRF) of the human immunodeficiency virus type 1 (HIV-1), the etiological agent of AIDS. CRF47_BF represents one of 19 CRFx_BFs and has a geographic focus in Spain, where it was first identified in 2010. Since its discovery, CRF47_BF has expanded considerably in Spain, predominantly through heterosexual contact (∼56% of the infections). Little is known, however, about the origin and diversity of this CRF or its epidemiological correlates, as very few samples have been available so far. This study conducts a phylogenetic analysis with representatives of all CRFx_BF sequence types along with HIV-1 M Group subtypes to validate that the CRF47_BF sequences share a unique evolutionary history. The CRFx_BF sequences cluster into a single, not well supported, clade that includes their dominant parent subtypes (B and F). This clade also includes subtype D and excludes sub-subtype F2. However, the CRF47_BF sequences all share a most recent common ancestor. Further analysis of this clade couples CRF47_BF protease-reverse transcriptase sequences and epidemiological data from an additional 87 samples collected throughout Spain, as well as additional CRF47_BF database sequences from Brazil and Spain to investigate the origin and phylodynamics of CRF47_BF. The Spanish region with the highest proportion of CRF47_BF samples in the data set was the Basque Country (43.7%) with Navarre next highest at 19.5%. We include in our analysis epidemiological data on host sex, mode of transmission, time of collection, and geographic region. The phylodynamic analysis indicates that CRF47_BF originated in Brazil around 1999-2000 and spread to Spain from Brazil in 2002-2003. The virus spread rapidly throughout Spain with an increase in population size from 2011 to 2015 and leveling off more recently. Three strongly supported clusters associated with Spanish regions (Basque Country, Navarre, and Aragon), together comprising 60.8% of the Spanish samples, were identified, one of which was also associated with transmission among men who have sex with men. The expansion in Spain of CRF47_BF, together with that of other CRFs and subtype variants of South American origin, previously reported, reflects the increasing relationship between the South American and European HIV-1 epidemics.
CRF47_BF是1型人类免疫缺陷病毒（HIV-1）的一种循环重组形式（CRF），HIV-1是艾滋病的病原体。CRF47_BF是19种CRFx_BF之一，主要集中在西班牙，于2010年在该国首次被发现。自发现以来，CRF47_BF在西班牙大幅传播，主要通过异性接触（约占感染病例的56%）。然而，由于目前可用的样本很少，关于这种CRF的起源、多样性及其流行病学关联知之甚少。本研究对所有CRFx_BF序列类型的代表以及HIV-1 M组亚型进行了系统发育分析，以验证CRF47_BF序列是否具有独特的进化史。CRFx_BF序列聚为一个单一的、支持度不高的进化枝，其中包括其主要的亲本亚型（B和F）。这个进化枝还包括D亚型，不包括F2亚亚型。然而，所有CRF47_BF序列都有一个最近的共同祖先。对这个进化枝的进一步分析将CRF47_BF蛋白酶-逆转录酶序列与从西班牙各地收集的另外87个样本的流行病学数据以及来自巴西和西班牙的其他CRF47_BF数据库序列相结合，以研究CRF47_BF的起源和系统动力学。数据集中CRF47_BF样本比例最高的西班牙地区是巴斯克地区（43.7%），其次是纳瓦拉，为19.5%。我们在分析中纳入了宿主性别、传播方式、采集时间和地理区域的流行病学数据。系统动力学分析表明，CRF47_BF于1999 - 2000年左右起源于巴西，并于2002 - 2003年从巴西传播到西班牙。该病毒在2011年至2015年期间随着人口规模的增加在西班牙迅速传播，最近趋于平稳。确定了与西班牙地区（巴斯克地区、纳瓦拉和阿拉贡）相关的三个支持度很高的聚类，共占西班牙样本的60.8%，其中一个聚类还与男男性行为者之间的传播有关。CRF47_BF在西班牙的传播，以及之前报道的其他源自南美的CRF和亚型变体的传播，反映了南美和欧洲HIV-1疫情之间日益增强的关联。
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