A single mutation in the Japanese encephalitis virus E protein (S123R) increases its growth rate in mouse neuroblastoma cells and its pathogenicity in mice.
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.
Tajima
Shigeru
S
Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan. stajima@nih.go.jp
Nerome
Reiko
R
Nukui
Yoko
Y
Kato
Fumihiro
F
Takasaki
Tomohiko
T
Kurane
Ichiro
I
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D009033:Culicidae; D018349:Encephalitis Viruses, Japanese / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense / Q000235:genetics; D009447:Neuroblastoma / Q000821:virology*; D013552:Swine; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics*; D010948:Viral Plaque Assay
D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C080628:glycoprotein E, Japanese encephalitis virus