WITHDRAWN: Retrospective investigation of origin, epidemiology and genetic characteristics of the dengue fever outbreak in Yunnan, China from 2017 to 2018

Abstract

Dengue has become a worldwide public health problem. In recent years, Dengue has broken out in multiple countries and regions. From 2017 to 2018, a dengue epidemic broke out in Yunnan of China and neighboring Southeast Asian countries (Laos and Myanmar). In this study, retrospective detection and genetic characterization of Dengue virus (DENV) strains were carried out between 2017 and 2018 in Yunnan, China. The dengue outbreak in Yunnan, China in 2017 was mainly caused by DENV1, while the dengue outbreak in 2018 was caused by DENV1 and DENV2. Among them, DENV2 plays a dominant role. Then, three complete sequence and ten envelope (E) gene sequences were obtained through PCR. YN/324 and YN/017 were isolated from Myanmar travelers, and YN/117 isolate from Laos travelers. In addition, YN/007 isolate has 13 nucleotides (10270 nt -10282 nt) deletions in the 3′ UTRs, which leads to significant changes in the RNA secondary structure. Multiple sequence alignment E gene sequences revealed that these locally isolates share high homology (> 99.5%) with the isolates from Myanmar and Laos. The phylogenetic divergence analysis also revealed that most of the local isolates were closely related to the isolates from Myanmar and Laos. YN/033 strain belong to genotype V of DENV1, and it was detected in Yunnan after 2013. Other isolates of DENV1 in this study were clustered in a branch representing genotype I. These isolates of DENV2 in this study belonged to Asia I, Asia II and Cosmopolitan. Further analyzed the relationship between the evolutionary tree branching and amino acid substitution of genotype revealed that multiple amino acid substitutions are related to the genetic evolution of DENV1 or DENV2, respectively. Similarly, genotype 1 of DENV1 can be divided into 4 subgroups based on the amino acid substitutions. In addition, twelve amino acid mutations are unique to the isolate in this study and have never been reported. Interestingly, recombination analysis found that both DENV1 and DENV2 isolates in this study had widespread intra-serotype recombination. In summary, the results of the epidemiological investigation implies that the dengue outbreak in Yunnan of China was mainly caused by imported cases. This research provides new reference for further research on the prevalence and the molecular epidemiology of DENV in Yunnan, China, as well as the variation characteristics of these novel isolates.