标题：Multiple transmission chains of coxsackievirus A4 co-circulating in China and neighboring countries in recent years: Phylogenetic and spatiotemporal analyses based on virological surveillance
作者：Chen, Peng; Wang, Haiyan; Tao, Zexin; Xu, Aiqiang; Lin, Xiaojuan; Zhou, Nan; Wang, Pei; Wang, Qian
作者机构：[Chen, Peng; Xu, Aiqiang; Zhou, Nan; Wang, Pei; Wang, Qian] Shandong Univ, Sch Publ Hlth, Dept Epidemiol, 44 Wenhuaxi Rd, Jinan 250012, Shandong, Peop 更多
通讯作者地址：[Xu, AQ]Shandong Ctr Dis Control & Prevent, 16992 Jingshi Rd, Jinan 250014, Shandong, Peoples R China.
来源：MOLECULAR PHYLOGENETICS AND EVOLUTION
关键词：Coxsackievirus A4; Acute flaccid paralysis; Hand, foot and mouth; disease; Phylogeny; Phylogeography
摘要：Coxsackievirus A4 (CV-A4) has been reported frequently in association with many infectious diseases and cases of hand, foot, and mouth disease potentially associated with CV-A4 infection are also identified. This study summarized the Shandong CV-A4 strains isolated from 25 years acute flaccid paralysis surveillance, with an emphasis on exploring the phylogenetic analyses and spatiotemporal dynamics of CV-A4 at the global scale. We sampled 43 CV-A4 isolates and utilized VP1 gene to construct phylogenetic trees. Further extensive Bayesian phylogeographic analysis was carried out to investigate the evolution of CV-A4 and understand the spatiotemporal diffusion around the world using BEAST and SPREAD software. Phylogenetic trees showed that CV-A4 emerged to be more active in recent decades and multiple transmission chains were co-circulating. The molecular clock analysis estimated a mean evolutionary rate of 6.4 x 10(-3) substitutions/site/year, and the estimated origin of CV-A4 around 1944. The phylogeographic analyses suggested the origin of CV-A4 could be in the USA, however regional dissemination was mainly located around the Asia-Europe region. The spatiotemporal dynamics of CV-A4 exhibited frequent viral traffic among localities, and virus from Shandong province seemed to have played a central role in spreading around China and neighboring countries. Our phylogenetic description and phylogeographic analyses indicate the importance of large spatial- and temporal-scale studies in understanding epidemiological dynamics of CV-A4, particularly the diffusion routes will be of great importance to global control efforts.