Spatiotemporal Characterizations of Dengue Virus in Mainland China: Insights into the Whole Genome from 1978 to 2011

Hao Zhang, Yanru Zhang, Rifat Hamoudi, Guiyun Yan, Xiaoguang Chen, Yuanping Zhou

Temporal-Spatial of dengue virus (DENV) analyses have been performed in previous epidemiological studies in mainland China, but few studies have examined the whole genome of the DENV. Herein, 40 whole genome sequences of DENVs isolated from mainland China were downloaded from GenBank. Phylogenetic analyses and evolutionary distances of the dengue serotypes 1 and 2 were calculated using 14 maximum likelihood trees created from individual genes and whole genome. Amino acid variations were also analyzed in the 40 sequences that included dengue serotypes 1, 2, 3 and 4, and they were grouped according to temporal and spatial differences. The results showed that none of the phylogenetic trees created from each individual gene were similar to the trees created using the complete genome and the evolutionary distances were variable with each individual gene. The number of amino acid variations was significantly different (p = 0.015) between DENV-1 and DENV-2 after 2001; seven mutations, the N290D, L402F and A473T mutations in the E gene region and the R101K, G105R, D340E and L349M mutations in the NS1 region of DENV-1, had significant substitutions, compared to the amino acids of DENV-2. Based on the spatial distribution using Guangzhou, including Foshan, as the indigenous area and the other regions as expanding areas, significant differences in the number of amino acid variations in the NS3 (p = 0.03) and NS1 (p = 0.024) regions and the NS2B (p = 0.016) and NS3 (p = 0.042) regions were found in DENV-1 and DENV-2. Recombination analysis showed no inter-serotype recombination events between the DENV-1 and DENV-2, while six and seven breakpoints were found in DENV-1 and DENV-2. Conclusively, the individual genes might not be suitable to analyze the evolution and selection pressure isolated in mainland China; the mutations in the amino acid residues in the E, NS1 and NS3 regions may play important roles in DENV-1 and DENV-2 epidemics.