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Abstract：
BACKGROUND: The strong invasiveness and rapid expansion of dengue virus (DENV) pose a great challenge to global public health. However, dengue epidemic patterns and mechanisms at a genetic scale, particularly in term of cross-border transmissions, remain poorly understood. Importation is considered as the primary driver of dengue outbreaks in China, and since 1990 a frequent occurrence of large outbreaks has been triggered by the imported cases and subsequently spread to the western and northern parts of China. Therefore, this study aims to systematically reveal the invasion and diffusion patterns of DENV-1 in Guangdong, China from 1990 to 2019.
METHODS: These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in Chinese mainland. The genetic population structure and epidemic patterns of DENV-1 circulating in Chinese mainland were characterized by phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework.
RESULTS: Multiple serotypes of DENV were co-circulating in Chinese mainland, particularly in Guangdong and Yunnan provinces. A total of 189 transmission clusters in 38 clades belonging to 22 subgenotypes of genotype I, IV and V of DENV-1 were identified, with 7 Clades of Concern (COCs) responsible for the large outbreaks since 1990. The epidemic periodicity was inferred from the data to be approximately 3 years. Dengue transmission events mainly occurred from Great Mekong Subregion-China (GMS-China), Southeast Asia (SEA), South Asia Subcontinent (SASC), and Oceania (OCE) to coastal and land border cities respectively in southeastern and southwestern China. Specially, Guangzhou was found to be the most dominant receipting hub, where DENV-1 diffused to other cities within the province and even other parts of the country. Genome phylogeny combined with epidemiological investigation demonstrated a clear local consecutive transmission process of a 5C1 transmission cluster (5C1-CN4) of DENV-1 in Guangzhou from 2013 to 2015, while the two provinces of Guangdong and Yunnan played key roles in ongoing transition of dengue epidemic patterns. In contextualizing within Invasion Biology theories, we have proposed a derived three-stage model encompassing the stages of invasion, colonization, and dissemination, which is supposed to enhance our understanding of dengue spreading patterns.
CONCLUSIONS: This study demonstrates the invasion and diffusion process of DENV-1 in Chinese mainland within a global genotyping framework, characterizing the genetic diversities of viral populations, multiple sources of importation, and periodic dynamics of the epidemic. These findings highlight the potential ongoing transition trends from epidemic to endemic status offering a valuable insight into early warning, prevention and control of rapid spreading of dengue both in China and worldwide.
METHODS: These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in Chinese mainland. The genetic population structure and epidemic patterns of DENV-1 circulating in Chinese mainland were characterized by phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework.
RESULTS: Multiple serotypes of DENV were co-circulating in Chinese mainland, particularly in Guangdong and Yunnan provinces. A total of 189 transmission clusters in 38 clades belonging to 22 subgenotypes of genotype I, IV and V of DENV-1 were identified, with 7 Clades of Concern (COCs) responsible for the large outbreaks since 1990. The epidemic periodicity was inferred from the data to be approximately 3 years. Dengue transmission events mainly occurred from Great Mekong Subregion-China (GMS-China), Southeast Asia (SEA), South Asia Subcontinent (SASC), and Oceania (OCE) to coastal and land border cities respectively in southeastern and southwestern China. Specially, Guangzhou was found to be the most dominant receipting hub, where DENV-1 diffused to other cities within the province and even other parts of the country. Genome phylogeny combined with epidemiological investigation demonstrated a clear local consecutive transmission process of a 5C1 transmission cluster (5C1-CN4) of DENV-1 in Guangzhou from 2013 to 2015, while the two provinces of Guangdong and Yunnan played key roles in ongoing transition of dengue epidemic patterns. In contextualizing within Invasion Biology theories, we have proposed a derived three-stage model encompassing the stages of invasion, colonization, and dissemination, which is supposed to enhance our understanding of dengue spreading patterns.
CONCLUSIONS: This study demonstrates the invasion and diffusion process of DENV-1 in Chinese mainland within a global genotyping framework, characterizing the genetic diversities of viral populations, multiple sources of importation, and periodic dynamics of the epidemic. These findings highlight the potential ongoing transition trends from epidemic to endemic status offering a valuable insight into early warning, prevention and control of rapid spreading of dengue both in China and worldwide.
摘要：
背景：登革热病毒（DENV）的强大侵袭性和快速扩张对全球公共卫生构成了巨大挑战。然而,登革热在遗传尺度上的流行模式和机制，特别是在跨境传输方面，仍然知之甚少。进口被认为是中国登革热暴发的主要驱动因素，自1990年以来，由输入性病例引发的大规模疫情频繁发生，随后蔓延到中国西部和北部。因此,本研究旨在系统地揭示DENV-1在广东的侵袭和扩散规律,中国从1990年到2019年。
方法：这些分析是对广东本地登革热病例的179个新组装基因组进行的，5152个E基因完整序列记载于中国年夜陆。在中国大陆传播的DENV-1的遗传种群结构和流行模式具有系统发育特征，系统地理，基于DENV-1E基因的全球统一基因分型框架的系统动力学。
结果：DENV的多种血清型在中国大陆共循环，特别是在广东省和云南省。共有38个分支中的189个传播簇，属于基因型I的22个亚型，鉴定了DENV-1的IV和V，自1990年以来，有7个关注分支（COC）负责大规模爆发。从数据推断流行周期约为3年。登革热传播事件主要发生在大湄公河次区域-中国(GMS-China)，东南亚(SEA),南亚次大陆（SASC），和大洋洲（OCE）分别位于中国东南部和西南部的沿海和陆地边界城市。特别是,广州被认为是最主要的收款枢纽，DENV-1扩散到省内其他城市，甚至全国其他地区。基因组系统发育结合流行病学调查显示，2013-2015年，广州有一个DENV-1的5C1传播群（5C1-CN4）的局部连续传播过程清晰，而广东和云南两省在登革热流行模式的持续转变中发挥了关键作用。在入侵生物学理论中的语境化，我们提出了一个衍生的三阶段模型，包括入侵阶段，殖民,和传播,这应该加强我们对登革热传播模式的理解。
结论：本研究证明了DENV-1在全球基因分型框架内在中国大陆的侵袭和扩散过程。表征病毒种群的遗传多样性，多种进口来源，和流行病的周期性动态。这些发现强调了从流行病到流行状态的潜在持续转变趋势，为早期预警提供了宝贵的见解。预防和控制登革热在中国和世界范围内的快速传播。
方法：这些分析是对广东本地登革热病例的179个新组装基因组进行的，5152个E基因完整序列记载于中国年夜陆。在中国大陆传播的DENV-1的遗传种群结构和流行模式具有系统发育特征，系统地理，基于DENV-1E基因的全球统一基因分型框架的系统动力学。
结果：DENV的多种血清型在中国大陆共循环，特别是在广东省和云南省。共有38个分支中的189个传播簇，属于基因型I的22个亚型，鉴定了DENV-1的IV和V，自1990年以来，有7个关注分支（COC）负责大规模爆发。从数据推断流行周期约为3年。登革热传播事件主要发生在大湄公河次区域-中国(GMS-China)，东南亚(SEA),南亚次大陆（SASC），和大洋洲（OCE）分别位于中国东南部和西南部的沿海和陆地边界城市。特别是,广州被认为是最主要的收款枢纽，DENV-1扩散到省内其他城市，甚至全国其他地区。基因组系统发育结合流行病学调查显示，2013-2015年，广州有一个DENV-1的5C1传播群（5C1-CN4）的局部连续传播过程清晰，而广东和云南两省在登革热流行模式的持续转变中发挥了关键作用。在入侵生物学理论中的语境化，我们提出了一个衍生的三阶段模型，包括入侵阶段，殖民,和传播,这应该加强我们对登革热传播模式的理解。
结论：本研究证明了DENV-1在全球基因分型框架内在中国大陆的侵袭和扩散过程。表征病毒种群的遗传多样性，多种进口来源，和流行病的周期性动态。这些发现强调了从流行病到流行状态的潜在持续转变趋势，为早期预警提供了宝贵的见解。预防和控制登革热在中国和世界范围内的快速传播。
