中东呼吸综合征冠状病毒 (MERS-CoV) 的内化不依赖DPP4细胞质尾部信号传递
Karthika Thankamani1, Divakar Shubham1, Gayatri Kandpal1
1Virology Scientific Research (VSR) Laboratory, School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram (IISER-TVM), Thiruvananthapuram, Kerala, India.
Npj viruses
|April 28, 2025
概括
对于中东呼吸综合征冠状病毒 (MERS-CoV) 进入宿主细胞来说,二乙酶4 (DPP4) 的细胞质尾部不需要. 即使DPP4尾巴发生突变或被删除,MERS-CoV仍然可以感染细胞.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 中东呼吸综合征冠状病毒 (MERS-CoV) 使用二乙酶4 (DPP4) 作为其细胞进入受体.
- DPP4 是一种II型膜蛋白,其特征是具有大型的ectodomain和短的细胞质尾巴.
- 在MERS-CoV入侵中DPP4细胞质尾巴的特定作用仍然在很大程度上未被调查.
研究的目的:
- 阐明DPP4细胞质尾巴在MERS-CoV宿主细胞进入中的功能.
- 确定DPP4细胞质尾巴是否对MERS-CoV结合和感染至关重要.
主要方法:
- 使用局部导向的突变发生法来制造缺乏或具有改变细胞质尾巴的DPP4突变物 (例如,ΔcytDPP4, ΔK6DPP4).
- HEK293T细胞被暂时和稳定地转化为表达野生型 (wtDPP4) 和突变DPP4蛋白质.
- 进行了MERS-CoV尖端蛋白结合试验和伪病毒感染试验,以评估病毒进入.
主要成果:
- 突变或删除DPP4细胞质尾巴并没有完全消除膜插入或MERS-CoV尖端蛋白结合.
- 虽然一些突变体表现出表面表达的减少,但MERS-CoV伪病毒仍然可以结合并感染表达这些DPP4变体的细胞.
- 具有被删除DPP4细胞质尾巴 (ΔcytDPP4) 的短暂和稳定表达细胞都易受MERS-CoV伪病毒感染.
结论:
- DPP4的细胞质尾巴对于MERS-CoV进入宿主细胞是不可或缺的.
- MERS-CoV与DPP4的结合不仅仅取决于细胞质尾部发起感染.
- 与DPP4或MERS-CoV尖端蛋白相互作用的额外宿主因素可能参与触发病毒内化.
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