Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Viruses. 2022 Jun 14;14(6):1299. doi: 10.3390/v14061299.
Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouse-adapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin-Darby canine kidney cells (London line) for use in challenge studies. We observed that virus grown in embryonated eggs was significantly more lethal in mice than the same virus grown in cell culture. Ten additional serial lung passages of one strain again showed virus grown in eggs was more lethal than virus grown in cells. Additionally, no mutations in the surface glycoprotein amino acid sequences correlated to differences in lethality. Our results suggest growth system can influence lethality of mouse-adapted IBVs after serial lung passaging. Further research can highlight improved mechanisms for developing animal disease models for IBV vaccine research.
尽管乙型流感病毒（IBV）每年在全球范围内都有影响，但宿主范围有限一直是开发易于获得的小动物疾病模型进行疫苗研究的一个障碍。通过在小鼠中连续肺部传代，可使适应小鼠的 IBV 产生高致病性病毒。先前的研究强调了整个病毒基因组中与致病性增加相关的氨基酸变化，但尚未确定一致的突变。我们旨在表明生长系统可以在小鼠适应的 IBV 致死性中发挥作用。两种 Yamagata 谱系 IBV 在小鼠肺部连续传代 10 次，然后在鸡胚或 Madin-Darby 犬肾细胞（伦敦谱系）中扩增，用于挑战研究。我们观察到在鸡胚中生长的病毒在小鼠中的致死性明显高于在细胞培养中生长的相同病毒。对一株病毒进行的另外 10 次连续肺部传代再次表明，在鸡蛋中生长的病毒比在细胞中生长的病毒更具致死性。此外，表面糖蛋白氨基酸序列中的突变与致死性差异无关。我们的结果表明，生长系统可以影响连续肺部传代后适应小鼠的 IBV 的致死性。进一步的研究可以突出开发用于 IBV 疫苗研究的动物疾病模型的改进机制。
