由SARS-CoV-2改变的TMPRSS2影响感染性和融合性
Bo Meng1,2, Adam Abdullahi1,2, Isabella A T M Ferreira1,2
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK.
Nature
|February 1, 2022
概括
Omicron BA.1 变种显示出抗体逃逸的增加,但仍然对抗病毒药物敏感. 第三剂疫苗恢复中和,与德尔塔相比,Omicron表现出细胞进入机制的改变.
科学领域:
- 病毒学
- 免疫学
- 病变发生
背景情况:
- 2021 年出现的 SARS-CoV-2 Omicron BA.1 变种具有众多的尖端蛋白突变.
- 与之前的Delta变种相比,Omicron表现出改变的抗原特性和细胞进入机制.
研究的目的:
- 研究Omicron BA.1突变对ACE2结合,抗体中和病毒进入途径的影响.
- 评估现有的疫苗和抗病毒药物对Omicron BA.1变种的疗效.
主要方法:
- 对Omicron BA.1和Delta尖端蛋白与ACE2的结合亲和力的比较分析.
- 通过疫苗引起的多克隆和治疗单克隆抗体中和的评估.
- 在人类细胞培养 (鼻腔,肺部,肠道) 中评估病毒复制.
- 尖端伪型病毒测试以确定细胞进入效率和对TMPRSS2和内细胞通路的依赖性.
主要成果:
- Omicron BA.1尖端蛋白具有较高的ACE2亲和力,但抗原性降低,导致两剂疫苗后显著的抗体逃避.
- 第三剂mRNA疫苗有效地恢复并扩大对Omicron BA.1的中和作用.
- 抗病毒药物雷德西维尔和莫尔努皮拉维尔对Omicron BA.1保持有效性.
- 与Delta相比,Omicron BA.1在鼻腔细胞中表现出类似的复制,但在肺和肠道细胞中复制率较低.
- 奥米克朗BA.1尖端蛋白在S1/S2的分裂效率较低,更多地依赖细胞进入的内细胞通路,而TMPRSS2的依赖性较低.
结论:
- Omicron BA.1 由于尖端蛋白处理效率低下以及细胞热带性偏离表达TMPRSS2的细胞而表现出改变的致病性.
- 目前的抗病毒疗法仍然有效,并对恢复对Omicron BA.1的保护至关重要.
相关概念视频
00:57Viral Recombination
22.3K
Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
22.3K
02:28Leaky Scanning
4.5K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
4.5K