title: An amino acid substitution (V3I) in the Japanese encephalitis virus NS4A protein increases its virulence in mice, but not its growth rate in vitro.
abstract: Our previous studies have shown that the Japanese encephalitis virus (JEV) strain Mie/40/2004 is the most virulent of the strains isolated by us in Japan from 2002 to 2004. Comparison of the amino acid sequence of Mie/40/2004 with those of low-virulence strains revealed that an isoleucine residue at position 3 of the Mie/40/2004 NS4A protein may increase viral pathogenicity. A recombinant virus with a single valine-to-isoleucine substitution (V3I) at position 3 in the low-virulence Mie/41/2002 background (rJEV-Mie41-NS4A(V3I)) exhibited increased virulence in mice compared with the Mie/41/2002 parent strain. The V3I mutation did not affect virus growth in several cell lines. These results demonstrate that the isoleucine at position 3 in the NS4A protein of Mie/40/2004 is responsible for its high virulence in vivo. This is the first report to show that an amino acid substitution in a flavivirus NS4A protein alters viral pathogenicity in mice.
authors.affiliation: Department of Pathology, Immunology and Microbiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.|Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Infection Control and Prevention, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.|Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nukui
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tajima
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Nerome
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Kato
authors.affiliation: Department of Pathology, Immunology and Microbiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.|National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Takasaki
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurane
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D004664:Encephalitis Virus, Japanese / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D004672:Encephalitis, Japanese / Q000821:virology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: D017361:Viral Nonstructural Proteins