Akabane virus nonstructural protein NSm regulates viral growth and pathogenicity in a mouse model

Yukari Ishihara, Chieko Shioda, Norasuthi Bangphoomi, Keita Sugiura, Kohei Saeki, Shumpei Tsuda, Tatsuya Iwanaga, Akiko Takenaka-Uema, Kentaro Kato, Shin Murakami, Kazuyuki Uchida, Hiroomi Akashi, Taisuke Horimoto

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1391-1397
Number of pages7
JournalJournal of Veterinary Medical Science
Volume78
Issue number9
DOIs
Publication statusPublished - 2016 Sep
Externally publishedYes

Keywords

  • Akabane virus
  • Nonstructural protein
  • Pathogenicity
  • Reverse genetics

ASJC Scopus subject areas

  • veterinary(all)

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