title: Akabane virus nonstructural protein NSm regulates viral growth and pathogenicity in a mouse model.
abstract: The biological function of a nonstructural protein, NSm, of Akabane virus (AKAV) is unknown. In this study, we generated a series of NSm deletion mutant viruses by reverse genetics and compared their phenotypes. The mutant in which the NSm coding region was almost completely deleted could not be rescued, suggesting that NSm plays a role in virus replication. We next generated mutant viruses possessing various partial deletions in NSm and identified several regions critical for virus infectivity. All rescued mutant viruses produced smaller plaques and grew inefficiently in cell culture, compared to the wild-type virus. Interestingly, although the pathogenicity of NSm deletion mutant viruses varied in mice depending on their deletion regions and sizes, more than half the mice died following infection with any mutant virus and the dead mice exhibited encephalitis as in wild-type virus-inoculated mice, indicating their neuroinvasiveness. Abundant viral antigens were detected in the brain tissues of dead mice, whereas appreciable antigen was not observed in those of surviving mice, suggesting a correlation between virus growth rate in the brain and neuropathogenicity in mice. We conclude that NSm affects AKAV replication in vitro as well as in vivo and that it may function as a virulence factor.
authors.affiliation: Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Chieko
authors.initials: C
authors.lastname: Shioda
authors.forename: Norasuthi
authors.initials: N
authors.lastname: Bangphoomi
authors.forename: Keita
authors.initials: K
authors.lastname: Sugiura
authors.forename: Kohei
authors.initials: K
authors.lastname: Saeki
authors.forename: Shumpei
authors.initials: S
authors.lastname: Tsuda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Akiko
authors.initials: A
authors.lastname: Takenaka-Uema
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kato
authors.forename: Shin
authors.initials: S
authors.lastname: Murakami
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Uchida
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Akashi
authors.forename: Taisuke
authors.initials: T
authors.lastname: Horimoto
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D002044:Bunyaviridae Infections / Q000473:pathology / Q000821:virology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004195:Disease Models, Animal; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics; D016851:Orthobunyavirus / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D014709:Vero Cells / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000502:physiology*
chemical_list: D017361:Viral Nonstructural Proteins