New genotype invasion of dengue virus serotype 1 drove massive outbreak in Guangzhou, China

Background: Dengue feveris 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 scale have not been extensively examined. Here, we assessed new genotypeinvasion of DENV-1 isolated from Guangzhou in China to evaluate associations with epidemic outbreaks. Methodology/Principal Findings: We used DENV-1 strains isolated from sera of dengue cases from 2002 to 2016 in Guangzhou for complete genome sequencing. A neighbor-joiningphylogenetic tree was constructed to elucidate the genotypecharacteristics and determine if new genotypeinvasion correlated with major outbreaks. In our study, a new genotypeinvasion event was observed during each significant outbreakperiod in 2002-2003, 2006-2007 and 2013-2014. GenotypeII was the main epidemic genotypein 2003 and before. Invasion of genotypeI in 2006 caused an unusual outbreakwith 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, genotypeIII was introduced to Guangzhou as a new genotypeinvasion responsible for 37340 cases with RR 541.73 (95%CI=417.78-702.45), after which genotypesI and III began co-circulating. Base mutations occurred after new genotypeinvasion, and the gene sequence of NS3protein 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/Significance: Genotypereplacement and co-circulation of multiple DENV-1 genotypeswere observed. New genotypeinvasion was highly correlated with local unusual outbreaks. In addition to DENV-1 genotypeI in the unprecedented outbreakin 2014, new genotypeinvasion by DENV-1 genotypeIII occurred in Guangzhou.