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在人类肺上皮细胞上区分SARS-CoV-2Omicron亚变体的细胞进入潜力

Revansiddha H Katte¹, Yuanyun Ao¹, Wang Xu¹

¹Department of Cellular and Molecular Biology, School of Medicine, University of Texas at Tyler Health Science Center, Tyler, TX 75708, USA.

|March 28, 2024

概括

最近的Omicron亚型,如XBB.1.5,在人类肺细胞中没有显著的进入优势,而不是早期的菌株. 从改变的尖端蛋白序列的免疫逃避,而不是细胞进入效率,可能驱动病毒健康.

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:

在SARS-CoV-2尖峰 (S) 糖蛋白对于病毒通过膜融合或内细胞分裂进入至关重要.
奥米克朗亚型具有许多S突变,影响传播能力,抗原性和融合性.
以前的研究经常使用工程细胞系,限制了对相关人类肺表皮的变异性输入的理解.

研究的目的:

系统地比较人类肺上皮细胞中占主导地位的Omicron亚变体的单一病毒进入细胞和细胞融合.
调查细胞类型和S蛋白加工在Omicron变异的进入效率中的作用.
为了确定最近的Omicron后代是否与早期的SARS-CoV-2变种相比拥有增强的入口或融合能力.

主要方法:

利用人类支气管上皮的BEAS-2B细胞作为宿主模型.
采用分离的NanoLuc聚变读取试验和S类伪型的lentivirus系统.
对比Omicron BA.1,BA.5,BQ.1.1,CH.1.1,XBB.1.5和XBB.1.16.5的进入和融合情况.

主要成果:

病毒进入细胞的效率因细胞类型而异;与BEAS-2B细胞相比,Omicron BA.1进入HEK293T-ACE2-TMPRSS2的速度较慢.
奥米克朗BA.1和后代比D614G更有效地进入BEAS-2B细胞,与Delta相比.
与Delta或早期的Omicron变种相比,最近的Omicron亚型在细胞进入或融合方面没有显著的优势.

结论:

细胞类型的依赖影响SARS-CoV-2变体的进入动态.
血融合仍然是Omicron亚变体的可行入口途径,通过血清蛋白酶治疗增强.
最近Omicron后代的身体适应性增加的主要驱动因素可能是由于抗原转移而导致的免疫逃避,而不是增强的细胞进入或融合.

关键词:

贝斯-2B 贝斯-2B 是一个欧米克朗XBBXBB是什么意思奥米克朗亚型的变种核聚变/核聚变性是指人类肺部上皮质尖子蛋白质是什么?病毒进入病毒细胞.

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