Related Experiment Video
Updated: Jun 18, 2026
Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses
Published on: December 29, 2015
A single mutation in the Japanese encephalitis virus E protein (S123R) increases its growth rate in mouse
Shigeru Tajima1, Reiko Nerome, Yoko Nukui
1Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan. stajima@nih.go.jp
Abstract:
We previously reported that the Japanese encephalitis virus (JEV) strain Mie/41/2002 has weak pathogenicity compared with the laboratory strain Beijing-1. To identify the determinants of its growth nature and pathogenicity, we produced intertypic viruses, rJEV(EB1-M41), rJEV(nEB1-M41) and rJEV(cEB1-M41), which contained the entire, the N-terminal, and the C-terminal half, respectively, of the Beijing-1 E region in the Mie/41/2002 background. The growth of rJEV(EB1-M41) in mouse neuroblastoma N18 cells and virulence in mice were similar to those of Beijing-1. rJEV(nEB1-M41) propagated in N18 cells to the same extent as did Beijing-1. Furthermore, we produced mutant viruses with single amino acid substitutions in the N-terminal half of the Mie/41/2002 E region. A Ser-123-Arg mutation in the Mie/41/2002 E protein exhibited significantly increased growth rate in N18 cells and virulence in mice. These results indicate that the position 123 in the E protein is responsible for determining the growth properties and pathogenicity of JEV.
Insights
Japanese encephalitis virus (JEV) pathogenicity is determined by specific viral proteins. A single amino acid change in the E protein significantly increased JEV
Area of Science:
- Virology
- Molecular Biology
- Pathogenesis
Background:
- Japanese encephalitis virus (JEV) strain Mie/41/2002 exhibits lower pathogenicity than the laboratory strain Beijing-1.
- Understanding the genetic determinants of JEV pathogenicity is crucial for developing effective control strategies.
Purpose of the Study:
- To identify the specific viral determinants responsible for the differential growth and pathogenicity of JEV strains.
- To elucidate the role of the E protein in JEV virulence.
Main Methods:
- Construction and characterization of intertypic recombinant JEVs (rJEVs) with defined genetic segments from Beijing-1 and Mie/41/2002 strains.
- Generation of single amino acid substitution mutants within the E protein of the Mie/41/2002 JEV strain.
- Assessment of viral growth kinetics in mouse neuroblastoma cells (N18) and evaluation of pathogenicity in a mouse model.
Main Results:
- Recombinant JEVs containing the entire or N-terminal half of the Beijing-1 E region in the Mie/41/2002 background partially restored growth and virulence.
- A specific mutation (Ser-123-Arg) in the N-terminal half of the Mie/41/2002 E protein significantly enhanced viral replication in N18 cells.
- This Ser-123-Arg mutation also led to increased pathogenicity in a mouse model.
Conclusions:
- The N-terminal half of the JEV E protein plays a critical role in determining viral growth properties and pathogenicity.
- Amino acid position 123 within the JEV E protein is a key determinant of JEV virulence and replication efficiency.
Related Concept Videos
01:26Encephalitis ll: Pathophysiology
01:25Arboviral Encephalitis