Mutations in the envelope protein of Japanese encephalitis virus affect entry into cultured cells and virulence in mice.
The nucleotide sequences of the envelope protein of the Kamiyama 1 strain of Japanese encephalitis (JE) virus and a passaged mutant (Kamiyama 2 strain) were determined. Two amino acid differences, Ser-Phe at residue 364 and Asn-Ile at residue 367, distinguished Kamiyama 2 from Kamiyama 1. Six neutralization-resistant variants were selected from these two strains using a JE species-specific monoclonal antibody with neutralization and hemagglutination-inhibition reactivities. All variants had a single amino acid substitution at residue 52 and significantly reduced reactivity with other JE species-specific monoclonal antibodies. The variants derived from Kamiyama 2 strain showed reduced virulence in 3-week-old mice after peripheral inoculation but were as virulent as the parent virus when inoculated intracranially. These variants also showed altered early virus-cell interaction but not replication and reproduction in Vero cells. These findings indicate that the mutations at residues 52, 364, and 367 affect early virus-cell interaction in Vero cells and virulence in mice.
Hasegawa
H
H
First Department of Internal Medicine, School of Medicine, Ehime University, Japan.
Yoshida
M
M
Shiosaka
T
T
Fujita
S
S
Kobayashi
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002478:Cells, Cultured; D004664:Encephalitis Virus, Japanese / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D004672:Encephalitis, Japanese / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D012367:RNA, Viral; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics*; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D012367:RNA, Viral; D014759:Viral Envelope Proteins