Abstract
BackgroundDengue fever is a mosquito-borne infectious disease that has caused major health problems. Variations in dengue virus (DENV) genes are important features of epidemic outbreaks. However, the associations of DENV genes with epidemic potential have not been extensively examined. Here, we assessed new genotype invasion of DENV-1 isolated from Guangzhou in China to evaluate associations with epidemic outbreaks.Methodology/principal findingsWe used DENV-1 strains isolated from sera of dengue cases from 2002 to 2016 in Guangzhou for complete genome sequencing. A neighbor-joining phylogenetic tree was constructed to elucidate the genotype characteristics and determine if new genotype invasion was correlated with major outbreaks. In our study, a new genotype invasion event was observed during each significant outbreak period in 2002–2003, 2006–2007, and 2013–2014. Genotype II was the main epidemic genotype in 2003 and before. Invasion of genotype I in 2006 caused an unusual outbreak with 765 cases (relative risk [RR] = 16.24, 95% confidence interval [CI] 12.41–21.25). At the middle and late stages of the 2013 outbreak, genotype III was introduced to Guangzhou as a new genotype invasion responsible for 37,340 cases with RR 541.73 (95% CI 417.78–702.45), after which genotypes I and III began co-circulating. Base mutations occurred after new genotype invasion, and the gene sequence of NS3 protein had the lowest average similarity ratio (99.82%), followed by the gene sequence of E protein (99.86%), as compared to the 2013 strain.Conclusions/significanceGenotype replacement and co-circulation of multiple DENV-1 genotypes were observed. New genotype invasion was highly correlated with local unusual outbreaks. In addition to DENV-1 genotype I in the unprecedented outbreak in 2014, new genotype invasion by DENV-1 genotype III occurred in Guangzhou.Graphical
Highlights
Dengue fever is a mosquito-borne infectious disease that has caused major health problems
All three genotypes have been observed in dengue virus (DENV)-1 outbreaks in China, and genotype III was believed to be new in China at the time of its detection
DENV-1 genotype III was first identified during the large outbreak in 2013–2014 in Guangzhou, demonstrating highest similarity with strains from India (JQ922548/India/2005, JQ917404/India/2009) and Singapore (KM403584/Singapore/2013), and no prior outbreaks of genotype III had been recorded in China
Summary
Dengue fever is a mosquito-borne infectious disease that has caused major health problems. Variations in dengue virus (DENV) genes are important features of epidemic outbreaks. The associations of DENV genes with epidemic potential have not been extensively examined. We assessed new genotype invasion of DENV-1 isolated from Guangzhou in China to evaluate associations with epidemic outbreaks. Dengue fever (DF), transmitted by the bite of infected Aedes mosquitoes, has become the most rapidly spreading arboviral disease in recent decades. The general roll-out of the only currently licensed vaccine, CYDTDV (Dengvaxia; Sanofi Pasteur, Lyon, France) is limited because pre-screening for dengue virus serostatus is required, as safety issues associated with increased hospitalization risk may occur for individuals who have never been infected with dengue before [6,7,8], and no specific interventions to treat the disease have been established. The sequence of each DENV genotype is not always fixed, and frequent variations, recombinations, and lineage turnover or replacement may occur because of selection pressure [9]
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