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含有酸的甘油脂扩大了肠道病毒-D68的受体谱
Ashley K Pereirinha da Silva1, Jacobus P van Trijp2, Anouk Montenarie1
1Department of Viroscience, Erasmus University Medical Center, 3015GDRotterdam, The Netherlands.
ACS infectious diseases
|July 9, 2025
概括
肠道病毒D68 (EV-D68) 可以使用化物作为入口受体,具有特定突变,使肝素硫酸盐 (HS) 结合. 不同的菌株表现出不同的酸结合,影响病毒进入和脱涂机制.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 传染性疾病 传染性疾病
背景情况:
- 肠道病毒D68 (EV-D68) 是一个日益严重的全球健康问题,与儿童的严重呼吸道疾病和急性软骨髓炎 (AFM) 相关.
- 了解EV-D68的组织热带性和病原性受限于对使病毒进入的宿主因素的不完全知识.
- 之前的研究确定了ICAM-5,化糖蛋白和肝素硫酸盐 (HS) 作为潜在的EV-D68受体.
研究的目的:
- 调查各种EV-D68菌株的受体要求,涉及所有菌株,重点是HS和sialosides.
- 阐明特定的病毒适应和宿主糖在EV-D68细胞进入中的作用.
- 检查具有明显受体结合偏好的EV-D68菌株之间脱涂机制的潜在差异.
主要方法:
- 使用甘氨酸阵列来分析各种EV-D68菌株与HS和sialosides的结合.
- 研究了细胞培养适应替代VP1蛋白对HS结合的影响.
- 采用抑制甘油脂生物合成和多价值甘油脂模仿剂来确认化物受体的使用.
- 使用Bafilomycin A1敏感度测试评估病毒脱涂机制.
主要成果:
- 所有与HS结合的EV-D68菌株都具有特定的VP1替代 (p271) 与正电荷氨基酸.
- EV-D68菌株表现出对N-甘氨酸上α2,6-结合的酸,对化物上α2,8-结合的酸或两者的偏好.
- 强化体结构被证实是特定EV-D68菌株的入口受体.
- 结合HS的菌株表现出巴菲洛米辛A1的最小抑制,与偏好类酶的菌株不同.
结论:
- EV-D68菌株可以利用disialoglycolipids (化物) 作为新的入口受体.
- 不同的EV-D68菌株表现出一种灵活而无序的酸结合谱.
- 病毒适应和宿主甘氨酸结构决定了EV-D68的热带和进入机制,可能会影响病变发生.
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