TY - JOUR
T1 - Akabane virus nonstructural protein NSm regulates viral growth and pathogenicity in a mouse model
AU - Ishihara, Yukari
AU - Shioda, Chieko
AU - Bangphoomi, Norasuthi
AU - Sugiura, Keita
AU - Saeki, Kohei
AU - Tsuda, Shumpei
AU - Iwanaga, Tatsuya
AU - Takenaka-Uema, Akiko
AU - Kato, Kentaro
AU - Murakami, Shin
AU - Uchida, Kazuyuki
AU - Akashi, Hiroomi
AU - Horimoto, Taisuke
N1 - Funding Information:
We thank Dr. M. Kubo (National Institute of Animal Health) for technical advice. We also thank Dr. N. Ito (Gifu University) for providing BHK/T7-9 cells and Dr. T. Tsuda (National Institute of Animal Health) for providing the antiserum against AKAV. This study was supported in part by a Research and Development Project for Application in Promoting New Policies in Agriculture, Forestry and Fisheries grant from the Ministry of Agriculture, Forestry and Fisheries, and a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Publisher Copyright:
© 2016 The Japanese Society of Veterinary Science.
PY - 2016/9
Y1 - 2016/9
N2 - 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.
AB - 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.
KW - Akabane virus
KW - Nonstructural protein
KW - Pathogenicity
KW - Reverse genetics
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U2 - 10.1292/jvms.16-0140
DO - 10.1292/jvms.16-0140
M3 - Article
C2 - 27181086
AN - SCOPUS:84989311670
VL - 78
SP - 1391
EP - 1397
JO - Journal of Veterinary Medical Science
JF - Journal of Veterinary Medical Science
SN - 0916-7250
IS - 9
ER -