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Clade C MERS-CoV驼菌株在病毒进入过程中蛋白酶利用方面存在差异

Helena Winstone^1,2, Helen Stillwell^1,2, Tiffany Tan³

¹Department of Microbiology, University of Pennsylvania.

bioRxiv : the preprint server for biology

|November 26, 2025

概括

Clade C MERS-CoV尖端显示了减少的裂和结合体形成. 这可能解释了这些驼病毒对人类的复制率较低,这表明了不同的选择压力.

科学领域:

病毒学病毒学
分子生物学分子生物学
流行病学流行病学

背景情况:

中东呼吸系统综合征冠状病毒 (MERS-CoV) 构成了流行病威胁.
类A和B MERS-CoV菌株导致人类爆发,起源于驼.
Clade C MERS-CoV菌株在非洲驼中传播,传播潜力不太清楚.

研究的目的:

调查MERS-CoV溢出中的潜在差异的分子和细胞基础.
将C类MERS-CoV的病毒进入机制与A类和B类菌株进行比较.
确定MERS-CoV热带和复制的遗传决定因素.

主要方法:

在S1/S2边界分析了MERS-CoV尖端蛋白质裂变.
评估了由不同的MERS-CoV基因组诱导的同位素形成.
通过TMPRSS2-介导途径在细胞系和初级培养物中评估病毒的进入.
绘制了负责TMPRSS2使用的分子区域.

主要成果:

与Clade A/B相比,Clade C MERS-CoV尖端在S1/S2边界的裂变效率较低.
大多数Clade C尖峰都诱导了减少的syncytium形成.
东非Clade C菌株显示TMPRSS2进入途径的利用受损.
减少的TMPRSS2使用被映射到Clade C尖端的N终端域 (NTD) 和子域2 (SD2).

结论:

在Clade C MERS-CoV中减少尖切割和同位素形成可能会导致人类复制率较低.
损伤的TMPRSS2-介导的进入是东非Clade C菌株差异性热带的关键因素.
在非洲和中东菌株之间可能存在对MERS-CoV尖端蛋白的地理上不同的选择压力.

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