Molecular characterization of the viral structural protein genes in the first outbreak of dengue virus type 2 in Hunan Province, inland China in 2018

Abstract

Background An unexpected dengue outbreak occurred in Hunan Province in 2018. This was the first dengue outbreak in this area of inland China, and 172 cases were reported. Methods To verify the causative agent of this outbreak and characterise the viral genes, the genes encoding the structural proteins C/prM/E of viruses isolated from local residents were sequenced followed by mutation and phylogenetic analysis. Recombination, selection pressure, potential secondary structure and three-dimensional structure analyses were also performed. Results Phylogenetic analysis revealed that all epidemic strains were of the cosmopolitan DENV-2 genotype and were most closely related to the Zhejiang strain (MH010629, 2017) and then the Malaysia strain (KJ806803, 2013). Compared with the sequence of DENV-2SS, 151 base substitutions were found in the sequences of 89 isolates; these substitutions resulted in 20 non-synonymous mutations, of which 17 mutations existed in all samples (two in the capsid protein, six in the prM/M proteins, and nine in the envelope proteins). Moreover, amino acid substitutions at the 602nd (E322:Q → H) and 670th (E390: N → S) amino acids may have enhanced the 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 in the epidemic strains compared with DENV-2SS. Meanwhile, five changes were found in helical regions. Minor changes were observed in helical transmembrane and disordered regions. The 429th amino acid of the E protein switched from a histamine (positively charged) to an asparagine (neutral) in all 89 isolated strains. No recombination events or positive selection pressure sites were observed. To our knowledge, this study is the first to analyse the genetic characteristics of epidemic strains in the first dengue outbreak in Hunan Province in 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 clarify the intrinsic geographical relatedness of DENV-2 and contribute to further research on pathogenicity and vaccine development.

Spatio-temporal evolution and trend prediction of the incidence of Class B notifiable infectious diseases in China: a sample of statistical data from 2007 to 2020

“…This indicates that we have achieved notable results in the prevention and control of infectious diseases in China, which is consistent with the results of previous studies [43]. According to the research analysis, the fact that the four provinces have not seen a decline in the incidence of Class B notifiable infectious diseases may be mainly related to their special geographical location and climatic conditions [44][45][46][47][48][49]. In spite of a certain economic boost in Tibet, a border region in the southwest, the increasing trade flows results in the bigger size of the mobile population, which leads to the problem of new and traditional infectious diseases and their increasingly prominent crossborder transmission.…”

A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness

“…The dengue patients from outpatient services was clinically diagnosed by an immune colloidal gold kit against DENV non-structural protein-1 (NS1) antigen (Guan et al, 2021). The information of dengue patients is showed in Table S2.…”

Genetic characterization of Dengue virus serotype 1 circulating in Reunion Island, 2019- 2021, and the Seychelles, 2015-2016

“…Such local micro-evolution events have been observed in Asia, as shown for instance in the Hunan province where several mutations were seen in DENV-2 outbreak (2018) after importation from neighboring areas having higher incidence of dengue (24). The micro-evolution event in either structural or non-structural proteins can be neutral or under positive or negative selection with an impact in disease epidemiology (24,25). Whether the mutations found in DENV-1 epidemic strain played a role in dengue severe cases observed in Reunion needs to be further investigated.…”

“…Moreover, the probable single introduction of the DENV-1 genotype I in Reunion was followed by a discrete micro-evolution event since fteen exclusive non-synonymous mutations were found in different proteins, including capsid, NS1, NS2B, NS3, NS4B, and NS5. Such local micro-evolution events have been observed in Asia, as shown for instance in the Hunan province where several mutations were seen in DENV-2 outbreak (2018) after importation from neighboring areas having higher incidence of dengue (24). The micro-evolution event in either structural or non-structural proteins can be neutral or under positive or negative selection with an impact in disease epidemiology (24,25).…”