Abstract
Background: An unexpected dengue outbreak occurred in the Hunan Province in 2018. This is the first dengue outbreak in this area of inland China resulting 172 infected. Methods: To verify the causative agent of this outbreak and investigate gene characterization, the structural protein C/prM/E genes of viruses isolated from local residents were sequenced followed by mutation, phylogenetic analysis. The recombination, selection pressure, potential secondary structure and three-dimensional structure analysis were also performed. Results: Phylogenetic analysis revealed that all epidemic strains were classified as the cosmopolitan DENV-2 genotype, closest to the Zhejiang strain (MH010629, 2017) and then Malaysia strain (KJ806803, 2013). Compared with the DENV-2SS, 151 base substitutions were found in 89 sequences of isolates, resulting in 20 nonsynonymous mutations, of which 17 mutations existed among all samples (two in capsid protein, six in prM/M, and nine in envelope proteins). Moreover, amino acid substitutions at 602 th (E322:Q→H) and 670 th (E390: N→S) may result in heightened virulence of the epidemic strains. One new DNA-binding site and five new protein binding sites were observed. Two polynucleotide-binding sites and seven protein binding sites were lost compared with DENV-2SS. Meanwhile, five changes were found in helix regions. The helical transmembrane and disordered regions have minor changes. Protein tertiary structure prediction revealed the 429 th amino acid of E proteins was switch from histamine (positively charged) to asparagines (neutral) in 89 isolate strains. No recombination events or positive selection pressure sites were detected. To our knowledge, this study is the first gene analysis of epidemic strain in the first dengue outbreak in Hunan Province, inland China. Conclusions: The causative agent is likely to come from Zhejiang Province, a neighbouring Province where dengue fever broke out in 2017. This study may help understand the intrinsic geographical relatedness of DENV-2 and contributes further to research on pathogenicity and vaccine development.