Genotype patterns and evolutionary rates: uncovering Japanese encephalitis virus spread across Asia's climate regions

Japanese Encephalitis Virus (JEV) is a highly endemic zoonotic virus, consistently found in Asia and parts of the Western Pacific, and it's a major cause of human encephalitis. JEV belongs to a family of antigenically related viruses such as West Nile Virus (WNV), Murray Valley encephalitis virus (MVEV), and Aichi Lake Fever Virus (ALFV) and is transmitted by mosquitoes. Persistent outbreaks of the disease necessitate detailed studies to understand their transmission dynamics and develop effective prevention strategies. This study explores the evolutionary dynamics and spatial transmission of JEV, concentrating on the envelope protein (E) structural gene sequences obtained from across Asia's diverse climatic regions. Evolutionary modeling of the JEV E gene revealed a higher evolutionary rate in tropical regions compared to temperate regions, with nucleotide substitution rates estimated at 1.12 × 10⁻³ per site per year for tropical regions and 5.284 × 10⁻⁴ for temperate regions. The time to the most recent common ancestor (tMRCA) was traced to 1796 from Korea for temperate regions, and 1865 from Indonesia for tropical regions. Among the five genotypes of JEV, Genotype I (GI) and III (GIII) were established all over Southeast Asia; moreover, GI revealed a higher evolutionary rate, reflecting its adaptability to diverse ecological niches. The phylogeographic analysis highlighted significant contributions to virus diffusion by China, Korea, and Japan in temperate zones and by Vietnam in tropical zones. By analyzing genetic sequences from various regions and time periods, this study delivered valuable intuitions into transmission pathways. The findings highlighted the necessity of ongoing surveillance and evolutionary monitoring to track the spread and emergence of novel variations of JEV, which are crucial not just for managing JEV outbreaks but also for guiding immunization programs and public health initiatives.