Phylodynamics unveils invading and diffusing patterns of dengue virus serotype-1 in Guangdong China from 1990 to 2019 under a global genotyping framework

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 have been triggered by the driven importation of more cases and subsequently spread to the western and northern parts of China. Methods To reveal the transmission mechanism, the genetic population structure and epidemic patterns of DENV-1 circulating in mainland China were characterized using phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework. These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in mainland China. Results Multiple serotypes of DENV were co-circulating in mainland China, 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 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. Conclusion This study demonstrates the invasion and diffusion process of DENV-1 in mainland China 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 the prevention and control of rapid spreading of dengue only if we are urgently formulate policies for early warning, prevention and control of the disease both in China and worldwide.