Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice.

Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice.
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DOI:
10.3390/v14061299
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发表时间:
2022-06-14
期刊:
Viruses
影响因子:
--
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--
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其他
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尽管乙型流感病毒(ibv)每年都对全球造成影响,但有限的宿主范围一直是开发易于获得的用于疫苗研究的小动物疾病模型的障碍。小鼠适应型IBV可通过小鼠肺部连续传代产生高致病性病毒。先前的研究强调了整个病毒基因组的氨基酸变化与致病性增加相关,但尚未确定一致的突变。我们的目的是证明生长系统可以在小鼠适应IBV致死中发挥作用。两个yamagata系ibv在小鼠肺中连续传代10次,然后在胚胎卵或Madin-Darby犬肾细胞(伦敦系)中扩增用于激攻研究。我们观察到,在胚胎卵中生长的病毒对小鼠的致死率明显高于在细胞培养中生长的病毒。另外10次对同一株病毒的连续肺传代再次表明,在鸡蛋中生长的病毒比在细胞中生长的病毒更致命。此外,表面糖蛋白氨基酸序列的突变与致死率的差异无关。我们的研究结果表明,生长系统可以影响小鼠适应性ibv在连续肺传代后的致死率。进一步的研究可以强调开发用于IBV疫苗研究的动物疾病模型的改进机制。
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.
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