The spatiotemporal migration of Genotype 1 JEV since the 1970s.

<p>The different panels represent temporal projections of reconstructed migration events in last 40 years (1970, 1978, 1981, 1990, 2000, 2003, 2006 and 2010, respectively). The different colors, yellow, green, light blue, blue, dark blue, purple, orange, red, dark red demonstrates for 1970, 1978, 1981, 1990, 2000, 2003, 2006 and 2010, respectively. The panels only show the tendency of migration events or partial migration events that have occurred up to a particular date, assuming that the virus migrates at a constant rate over the inferred time span of the branch. Blue circles mark the hot point of migration events. AF, Afghanistan; PK, Pakistan; IN, India; NP, Nepal; BT, Bhutan; BG, Bangladesh; BM, Burma; TH, Thailand; LA, Laos; VN, Vietnam; KH, Cambodia; MY, Malaysia; ID, Indonesia; PP, Papua New Guinea; AU, Australia; KP, North Korea; KR, South Korea; JP, 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.</p

Southernmost Asia Is the Source of Japanese Encephalitis Virus (Genotype 1) Diversity from which the Viruses Disperse and Evolve throughout Asia

<div><p>Background</p><p>Although a previous study predicted that Japanese encephalitis virus (JEV) originated in the Malaysia/Indonesia region, the virus is known to circulate mainly on the Asian continent. However, there are no reported systematic studies that adequately define how JEV then dispersed throughout Asia.</p><p>Methodology/Principal Findings</p><p>In order to understand the mode of JEV dispersal throughout the entire Asian continent and the factors that determine the dispersal characteristics of JEV, a phylogenetic analysis using Bayesian Markov chain Monte Carlo simulations was conducted on all available JEV E gene sequences in GenBank, plus strains recently isolated in China. Here we demonstrate for the first time that JEV lineages can be divided into four endemic cycles, comprising southern Asia, eastern coastal Asia, western Asia, and central Asia. The isolation places of the viruses in each endemic cycle were geographically independent regardless of years, vectors, and hosts of isolation. Following further analysis, we propose that the southernmost region (Thailand, Vietnam, and Yunnan Province, China) was the source of JEV transmission to the Asian continent following its emergence. Three independent transmission routes from the south to north appear to define subsequent dispersal of JEV. Analysis of JEV population dynamics further supports these concepts.</p><p>Conclusions/Significance</p><p>These results and their interpretation provide new insights into our understanding of JEV evolution and dispersal and highlight its potential for introduction into non-endemic areas.</p></div

Japanese encephalitis in different geomorphic units, 1963–1975.

<p>QTP: the Qinghai-Tibet Plateau; LP: the Loess Plateau; YGP: the Yunnan-Guizhou Plateau; IMP: the Inner Mongolian Plateau; NECP: the Northeast China Plain; NCP: the North China Plain; YRP: the Yangtze River Plain; PRDP: the Pearl River Delta Plain.</p

Temporal distribution of JEV (genotype 1) in four endemic cycles (based on the time spots given by skyline plots).

<p>Temporal distribution of JEV (genotype 1) in four endemic cycles (based on the time spots given by skyline plots).</p

Maximum clade credibility tree for E gene sequences of genotype 1 JEV.

<p>Seven clusters were identified and estimated TMRCAs of these clusters (with their 95% HPD values in parentheses) are shown. Four endemic cycles were grouped based on the geographical locations of JEV strains in each cluster. Red, blue, olive and turquoise were used to mark strains from southernmost Asia, eastern coastal Asia, western Asia, and central Asia, respectively. Posterior probability values of each cluster and endemic cycles were showed in the right of the nodes. In order to present all available sequences in the tree, black triangles were used to condense strains with the same isolation place and similar isolation times.</p

Bayesian skyline plots for genotype 1 JEV.

<p>Highlighted areas correspond to 95% HPD intervals.</p

Dispersal characteristics of genotype 1 JEV based on phylogenetic analysis.

<p>Gray shadow presents the location of JEV strains used in this study; emboldened circle represents southern Asia endemic cycle established in the JEV transmission source area; red circles presented as dashed lines, intact lines circle and square dot lines represent west Asia, central Asia and east coastal Asia JEV endemic cycles, respectively; blue boxes presented as dashed lines, intact lines and square dots represent bird migration routes in Asia and they coincide with JEV endemic cycles; green dotted lines illustrate the potential dispersal directions of JEV in the future. CN, China; JP, Japan; KR, South Korea; IN, India; VN, Vietnam; TH, Thailand; KH, Cambodia; MY, Malaysia; ID, Indonesia; AU, Australia.</p

Climatic factors and Japanese encephalitis in different geomorphic units.

<p>(A) Comparison of the JE incidence in different geomorphic units shows that JE incidence in the plains was higher than that in the plateaus during 1963–1975. (B) The differences among eight geomorphic units in JE incidence and summer rainfall in 1971. There were no JE reported cases in the QTP and the IMP in 1971. Due to the affection of the southwest monsoon in summer, the YGP shows abundant summer rainfall. (C) The differences among eight geomorphic units in JE incidence and summer temperature in 1971. The summer temperature in the QTP was below 10°C in 1971 because of its high altitude (4000–5000 m).</p

Division of geomorphic units included in this study.

<p>Region 1 represents the Qinghai-Tibet Plateau (QTP); Region 2 represents the Loess Plateau (LP); Region 3 represents the Yunnan-Guizhou Plateau (YGP); Region 4 represents the Inner Mongolian Plateau (IMP); Region 5 represents the Northeast China Plain (NECP); Region 6 represents the North China Plain (NCP); Region 7 represents the Yangtze River Plain (YRP); Region 8 represents the Pearl River Delta Plain (PRDP).</p

The regional distribution of JEV (genotype 1) isolates in four endemic cycles.

<p>Note: TMRCA, the most recent common ancestor; KH, Cambodia; TH, Thailand; VN, Vietnam; AU, Australia; S-MC, southern mainland China; E-MC, eastern mainland China; N-MC, northern mainland China; W-MC, western mainland China; TW, Taiwan; KR, South Korea; JP, Japan; IN, India.</p