Akabane virus nonstructural protein NSm regulates viral growth and pathogenicity in a mouse model
Akabane virus nonstructural protein NSm regulates viral growth and pathogenicity in a mouse model
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DOI：
10.1292/jvms.16-0140
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发表时间：
2016-09-01
影响因子：
1.2
通讯作者：
Horimoto, Taisuke
中科院分区：
文献类型：
--
作者：
Ishihara, Yukari;Shioda, Chieko;Horimoto, Taisuke
赤羽病毒（AKAV）的非结构蛋白NSm的生物学功能尚不清楚。本研究通过反向遗传学方法获得了一系列NSm缺失突变病毒，并对它们的表型进行了比较。NSm编码区几乎完全缺失的突变体不能被拯救，这表明NSm在病毒复制中起作用。我们接下来产生了在NSm中具有各种部分缺失的突变病毒，并鉴定了对病毒感染性至关重要的几个区域。与野生型病毒相比，所有获救的突变病毒产生较小的噬斑，并且在细胞培养中生长效率低下。有趣的是，尽管NSm缺失突变病毒的致病性在小鼠中根据其缺失区域和大小而变化，但超过一半的小鼠在感染任何突变病毒后死亡，并且死亡小鼠表现出与野生型病毒接种小鼠相同的脑炎，表明其神经侵袭性。在死亡小鼠脑组织中检测到丰富的病毒抗原，而在存活小鼠脑组织中未观察到明显的抗原，表明病毒在脑中的生长速率与小鼠的神经致病性之间存在相关性。我们的结论是，NSm影响AKAV复制在体外以及在体内，它可能作为一个毒力因子。
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.