Tracing the spatiotemporal phylodynamics of Japanese encephalitis virus genotype I throughout Asia and the western Pacific

BackgroundJapanese encephalitis virus (JEV; Flaviridae: Flavivirus) causes Japanese encephalitis (JE), which is the most important arboviral disease in Asia and the western Pacific. Among the five JEV genotypes (GI-IV), GI has dominated traditional epidemic regions in the past 20 years. We investigated the transmission dynamics of JEV GI through genetic analyses. MethodsWe generated 18 JEV GI near full length sequences by using multiple sequencing approaches from mosquitoes collected in natural settings or from viral isolates obtained through cell culture. We performed phylogenetic and molecular clock analyses to reconstruct the evolutionary history by integrating our data with 113 publicly available JEV GI sequences. ResultsWe identified two subtypes of JEV GI (GIa and GIb), with a rate of 5.94 x 10(-4) substitutions per site per year (s/s/y). At present, GIa still circulates within a limited region, exhibited no significant growth, the newest strain was discovered in China (Yunnan) in 2017, whereas most JEV strains circulating belong to the GIb clade. During the past 30 years, two large GIb clades have triggered epidemics in eastern Asia: one epidemic occurred in 1992 [95% highest posterior density (HPD) = 1989-1995] and the causative strain circulates mainly in southern China (Yunnan, Shanghai, Guangdong, and Taiwan) (Clade 1); the other epidemic occurred in 1997 (95% HPD = 1994-1999) and the causative strain has increased in circulation in northern and southern China during the past 5 years (Clade 2). An emerging variant of Clade 2 contains two new amino acid markers (NS2a-151V, NS4-169K) that emerged around 2005; this variant has demonstrated exponential growth in northern China. ConclusionJEV GI stain circulating in Asia have shifted during the past 30 years, spatiotemporal differences were observed among JEV GI subclade. GIa is still circulating within a limited range, exhibite no significant growth. Two large GIb clades have triggered epidemics in eastern Asia, all JEV sequences identified in northern China during the past 5 years were of the new emerging variant of G1b-clade 2. Author summaryAlthough Japanese encephalitis virus (JEV) genotype I (GI) has circulated in Asia and the western Pacific during the past 30 years, little is known regarding its evolution, geographical distribution, and epidemiology, especially the recent years. To address this knowledge gap, we performed a phylogenetic analysis using all full open reading frame JEV sequences assembled thus far, including 113 viral sequences sampled from eight countries during the past 42 years. We revealed spatiotemporal differences in spread among JEV GI subclades; identified amino acid markers for different clades; made an in-depth study on the evolution of GIb, described the geographical distribution of the recent active GIb clade 2 and identified its emerging variant.

Automated summary

Through genetic analysis, it was found that the transmission dynamics of Japanese encephalitis virus (JEV) genotype I (GI) have changed in Asia, with GIa still circulating within a limited range and exhibiting no significant growth, while GIb has triggered two epidemics in eastern Asia.