Insights into the evolutionary history of Japanese encephalitis virus (JEV) based on whole-genome sequences comprising the five genotypes

Background: Japanese encephalitis virus (JEV) is the etiological agent of Japanese encephalitis (JE), one of the most serious viral encephalitis worldwide. Five genotypes have been classified based on phylogenetic analysis of the viral envelope gene or the complete genome. Previous studies based on four genotypes have reported that in evolutionary terms, genotype 1 JEV is the most recent lineage. However, until now, no systematic phylogenetic analysis was reported based on whole genomic sequence of all five JEV genotypes. Findings: In this study, phylogenetic analysis using Bayesian Markov chain Monte Carlo simulations was conducted on the whole genomic sequences of all five genotypes of JEV. The results showed that the most recent common ancestor (TMRCA) for JEV is estimated to have occurred 3255 years ago (95% highest posterior density [HPD], -978 to-6125 years). Chronologically, this ancestral lineage diverged to produce five recognized virus genotypes in the sequence 5, 4, 3, 2 and 1. Population dynamics analysis indicated that the genetic diversity of the virus peaked during the following two periods: 1930-1960 and 1980-1990, and the population diversity of JEV remained relatively high after 2000. Conclusions: Genotype 5 is the earliest recognized JEV lineage, and the genetic diversity of JEV has remained high since 2000.