对于merbecovirus MjHKU4r-CoV-1的受体识别和广泛宿主热带的分子基础
Zhennan Zhao1, Xin Li1, Yan Chai1
1CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
EMBO reports
|June 14, 2024
概括
一种新的松鼠冠状病毒,MjHKU4r-CoV-1,通过DPP4受体感染人类细胞. 特定的CD26受体位点决定了其广泛的宿主范围,这对于理解和预防未来的疫情至关重要.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 病毒进入的分子机制
背景情况:
- 一种新型的松鼠起源的MERS类冠状病毒MjHKU4r-CoV-1已被确定.
- 这种病毒与蝙蝠HKU4-CoV密切相关,在人类器官和转基因小鼠中表现出感染性.
- MjHKU4r-CoV-1利用双基酶4 (DPP4,也称为CD26) 受体进入,并表现出广泛的宿主热带性.
研究的目的:
- 阐明MjHKU4r-CoV-1受体结合的分子机制.
- 为了确定控制病毒宿主范围的决定因素.
- 了解MjHKU4r-CoV-1与其人类受体相互作用的结构基础.
主要方法:
- 确定了与人类CD26 (hCD26) 复合的MjHKU4r-CoV-1尖端 (S) 蛋白受体结合域 (RBD) 的晶体结构.
- 评估了MjHKU4r-CoV-1对各种动物受体的结合能力.
- 在CD26残留物上进行了突变发生分析和同质模型.
主要成果:
- 该研究揭示了MjHKU4r-CoV-1与hCD26受体结合的结构基础.
- 在CD26上特定的残留部位 (位置291,292,294,295,336和344) 被确定为MjHKU4r-CoV-1宿主范围的关键决定因素.
- 该病毒表现出广泛的热带性,与多个动物受体相互作用.
结论:
- 这些发现提供了对MjHKU4r-CoV-1的受体结合机制和宿主热带的详细了解.
- 确定了关键的CD26残留物,这对于确定这种松鼠冠状病毒的宿主范围至关重要.
- 这项研究提高了对未来可能发生的MjHKU4r-CoV-1或相关病毒爆发的准备.
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