Emergence of genotype I of Japanese encephalitis virus as the dominant genotype in Asia

Abstract

Japanese encephalitis virus (JEV), a mosquito-borne zoonotic pathogen, is one of the major causes of viral encephalitis worldwide. Previous phylogenetic studies based on the envelope protein indicated that there are four genotypes, and surveillance data suggest that genotype I is gradually replacing genotype III as the dominant strain. Here we report an evolutionary analysis based on 98 full-length genome sequences of JEV, including 67 new samples isolated from humans, pigs, mosquitoes, midges. and bats in affected areas. To investigate the relationships between the genotypes and the significance of genotype I in recent epidemics, we estimated evolutionary rates, ages of common ancestors, and population demographics. Our results indicate that the genotypes diverged in the order IV, III, II, and I and that the genetic diversity of genotype III has decreased rapidly while that of genotype I has increased gradually, consistent with its emergence as the dominant genotype.

FIG. 1.

Worldwide distribution of identified JEV cases. The provinces in China and the other countries from which JEV was isolated and used in this study are shaded. AF, Afghanistan; PK, Pakistan; IN, India; NP, Nepal; BT, Bhutan; BG, Bangladesh; BM, Burma; TH, Thailand; LA, Laos; VM, Vietnam; CB, Cambodia; MY, Malaysia; ID, Indonesia; PP, Papua New Guinea; AS, Australia; KN, North Korea; KS, South Korea; JA, Japan. Chinese provinces: HLJ, Heilongjiang Province; JL, Jilin Province; LN, Liaoning Province; NM, Neimenggu; XJ, Xinjiang; BJ, Beijing, TJ, Tianjin; HeB, Hebei Province; SX, Shanxi Province; SaX, Shaanxi Province; GS, Gansu Province; QH, Qinghai Province; NX, Ningxia; SD, Shandong Province; SH, Shanghai; JS, Jiangsu Province; AH, Anhui Province; HeN, Henan Province; XZ, Xizang; ZJ, Zhejiang Province; JX, Jiangxi Province; HuB, Hubei Province; CQ, Chongqing; SC, Sichuan Province; HuN, Hunan Province; GZ, Guizhou Province; YN, Yunnan Province; FJ, Fujian Province; GD, Guangdong Province; GX, Guangxi; HN, Hainan; TW, Taiwan; MG, Mongolia;.

FIG. 2.

Maximum clade credibility tree for 98 whole-genome sequences of JEV. Consistent with previous studies, the tree identifies four distinct lineages: genotype I (GI) (red), genotype II (yellow), genotype III (blue), and genotype IV (green). Estimated TMRCAs of these lineages (with their 95% HPD values in parentheses) are shown.

FIG. 3.

(a and b) Bayesian skyline plots for genotype III (a) and genotype I (b). Highlighted areas correspond to 95% HPD intervals. The broad 95% HPD for genotype I is a consequence of the sequence set used in the estimation. (c) Medians of the skyline plots for both genotypes drawn on the same scale. Dotted red line, genotype I; solid blue line, genotype III; dashed green line, ratio of the number of genotype I isolates to the number of genotype III isolates deposited in GenBank by year. The blue arrow marks the earliest isolate of genotype III; the red arrow marks the earliest isolate of genotype I. The order of magnitude drop in the estimated genetic diversity of genotype I is matched by a corresponding order of magnitude increase in the ratio of genotype I to genotype III isolates. See the text for full details.