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Published on: December 29, 2015
Molecular phylogenetic and evolutionary analyses of Muar strain of Japanese encephalitis virus reveal it is the
Manal A F Mohammed1, Sareen E Galbraith, Alan D Radford
1Brain Infections Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
Abstract:
Japanese encephalitis virus (JEV) is the most important cause of epidemic encephalitis worldwide but its origin is unknown. Epidemics of encephalitis suggestive of Japanese encephalitis (JE) were described in Japan from the 1870s onwards. Four genotypes of JEV have been characterised and representatives of each genotype have been fully sequenced. Based on limited information, a single isolate from Malaysia is thought to represent a putative fifth genotype. We have determined the complete nucleotide and amino acid sequence of Muar strain and compared it with other fully sequenced JEV genomes. Muar was the least similar, with nucleotide divergence ranging from 20.2 to 21.2% and amino acid divergence ranging from 8.5 to 9.9%. Phylogenetic analysis of Muar strain revealed that it does represent a distinct fifth genotype of JEV. We elucidated Muar signature amino acids in the envelope (E) protein, including E327 Glu on the exposed lateral surface of the putative receptor binding domain which distinguishes Muar strain from the other four genotypes. Evolutionary analysis of full-length JEV genomes revealed that the mean evolutionary rate is 4.35 × 10(-4) (3.4906 × 10(-4) to 5.303 × 10(-4)) nucleotides substitutions per site per year and suggests JEV originated from its ancestral virus in the mid 1500s in the Indonesia-Malaysia region and evolved there into different genotypes, which then spread across Asia. No strong evidence for positive selection was found between JEV strains of the five genotypes and the E gene has generally been subjected to strong purifying selection.
Insights
Japanese encephalitis virus (JEV), a major cause of epidemic encephalitis, has a newly identified fifth genotype. Evolutionary analysis suggests JEV originated in the Indonesia-Malaysia region around the mid-1500s.
Area of Science:
- Virology
- Molecular Evolution
- Epidemiology
Background:
- Japanese encephalitis virus (JEV) is a significant global cause of epidemic encephalitis.
- The evolutionary origins and genetic diversity of JEV remain incompletely understood.
- Previous studies identified four JEV genotypes, with a potential fifth genotype suggested by limited data.
Purpose of the Study:
- To determine the complete nucleotide and amino acid sequence of the Muar strain, a putative JEV genotype V isolate.
- To phylogenetically analyze the Muar strain and compare it with other JEV genotypes.
- To investigate the evolutionary history and origin of JEV.
Main Methods:
- Whole-genome sequencing of the JEV Muar strain.
- Comparative sequence analysis of JEV genomes (nucleotide and amino acid divergence).
- Phylogenetic analysis to determine JEV genotype classification.
- Evolutionary rate estimation and molecular clock analysis.
Main Results:
- The Muar strain represents a distinct fifth genotype of JEV, showing significant sequence divergence from other genotypes.
- Specific amino acid signatures in the envelope (E) protein, such as E327 Glu, distinguish the Muar strain.
- Evolutionary analysis indicates JEV originated in the Indonesia-Malaysia region in the mid-1500s.
- The envelope (E) gene is under strong purifying selection, with no evidence of positive selection among genotypes.
Conclusions:
- The Muar strain confirms the existence of a fifth JEV genotype.
- The findings provide insights into the origin and early evolution of JEV in Southeast Asia.
- Understanding JEV genotype diversity and evolution is crucial for disease control and prevention strategies.
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