Phylogeography of Japanese Encephalitis Virus: Genotype Is Associated with Climate: e2411

Abstract

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate.

Author Summary

Although Japanese encephalitis virus (JEV) is a major cause of death and disability throughout tropical and temperate Asia, little is known about the evolution, geographical distribution and epidemiology of the five JEV genotypes (genetically distinct groups). To address this gap in our knowledge, we performed a genetic-based geographical analysis using the largest JEV sequence dataset assembled to date, including 487 viral sequences sampled from 12 countries over 75 years. We showed that both the newly and previously dominant genotypes of JEV are associated with temperate climates and are maintained throughout the cold winter months in northern Asia, likely by hibernating mosquitoes (survive throughout the winter), vertical transmission in mosquitoes (female to offspring), cold-blooded vertebrates and/or bats.

Citation: Schuh AJ,...