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与Omicron SARS-CoV-2变种相比,N-glycan修改对祖先的尖端表达,病毒感染性和中和敏感性的影响
Sabrina Lusvarghi1, Charles B Stauft1, Russell Vassell1
1Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring Maryland, United States of America.
PLoS pathogens
|November 9, 2023
概括
在SARS-CoV-2尖端蛋白上的甘氨酸对Omicron变体的感染性和抗体中和产生了重大影响. 特定的甘氨酸损失比其他变种更能降低Omicron的感染力,影响病毒进入和抗体易感性.
科学领域:
- 病毒学 病毒学
- 葡萄糖生物学 葡萄糖生物学
- 免疫学 免疫学 免疫学
背景情况:
- 在SARS-CoV-2的尖端糖蛋白中,有许多N-链接的糖化位点,这些位点对病毒功能至关重要.
- 了解个体甘氨酸如何影响Omicron变体的进入和中和对于治疗开发至关重要.
研究的目的:
- 为了比较Omicron BA.1和D614G尖端蛋白中特定的甘氨酸删除/修改的影响.
- 调查对尖端表达,加工,结合,感染力和抗体中和的影响.
主要方法:
- 使用修改的尖端蛋白 (Omicron BA.1,D614G) 制作伪病毒.
- 对尖端表达,加工,结合和伪病毒感染性的测试.
- 使用治疗性单克隆抗体进行中和测定.
- 在kifunensine的存在下,与真实的SARS-CoV-2变体进行生长实验.
主要成果:
- 在N717和N801处失去甘氨酸显著降低了Omicron伪病毒的感染力,与受损的尖端处理和整合相关.
- 与Oligomannose丰富的Omicron伪病毒变得非传染性,与D614G或Delta变种不同.
- 基宁素治疗导致活体Omicron BA.1.1的标位减少比delta或D614GSARS-CoV-2更大.
- 甘氨酸的删除对抗体中和功效和各个变体的最大中和作用有差异.
结论:
- 特定于SARS-CoV-2变种的甘氨酸相互作用影响尖端蛋白功能,病毒感染性和抗体中和易感性.
- 甘氨酸的成分显著影响治疗抗体对不同SARS-CoV-2变体的疗效.
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