复杂的N-甘氨酸对H7型流感A病毒的物种间传播很重要
Cindy M Spruit1, Diana I Palme2, Tiehai Li3
1Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Journal of virology
|March 12, 2024
概括
适应N-glycolylneuraminic acid (NeuGc) 结合的马流感A病毒 (IAV) 血素突变使得禽类H7 IAVs通过结合特定的N-glycans感染和,从而促进潜在的物种间传播.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 流感A型病毒 (IAV) 适应其血凝素 (HA) 蛋白来克服物种障碍,主要是通过改变与酸受体的结合.
- 鸟类和人类的IAV通常会结合N-乙神经胺酸 (NeuAc),而马类IAV则更喜欢N-糖神经胺酸 (NeuGc).
- 了解HA适应对于预测IAV宿主热带和物种间传播潜力至关重要.
研究的目的:
- 调查先前在禽类H7IAV中发现的马类NeuGc适应突变对禽类宿主病毒复制和毒性的影响.
- 为了阐明这些突变的鸟类H7 HAs. 的受体结合特异性.
- 评估与马匹适应的H7 IAV的跨物种传播潜力.
主要方法:
- 在和的细胞中进行体外复制试验.
- 在和身上进行体内研究,以评估病毒的毒性,死亡率和分泌率.
- 糖甘微阵列和流细胞计分析以确定H7 HAs的受体结合特异性.
主要成果:
- 马类NeuGc适应突变对细胞的复制产生了负面影响,但不影响子细胞的复制,同时增强了马细胞的复制.
- 突变降低了的毒性和死亡率;尽管子看起来健康,但子显示病毒的流失持续时间很长.
- 突变的禽类H7 HAs在三天线N-甘氨酸上与α2,3-结合的Neuac和sialyl-LewisX结合,解释了和的感染.
结论:
- 将NeuGc适应的H7 IAV与三天线N-甘氨酸的结合有助于病毒复制和在和子中脱落.
- 这些发现强调了细受体特异性在IAV宿主适应中的重要性.
- 这项研究表明,与马匹适应的H7 IAV的物种间传播可能存在一种潜在的机制.
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