当SARS-CoV-2在免疫原始小鼠中反复传递时,它迅速演变为特定的表型差异
Julian Daniel Sunday Willett1,2,3, Annie Gravel4, Isabelle Dubuc4
1Quantitative Life Sciences Ph.D. Program, McGill University, Montreal, QC, Canada.
Communications biology
|February 16, 2024
概括
病毒进化驱动SARS-CoV-2的持续性,增加严重性和免疫逃避. 诸如Delta等变体中的S371F等特定突变有助于抗体耐药性和干扰素抑制,影响公共卫生策略.
科学领域:
- 病毒学 病毒学
- 进化生物学 进化生物学
- 免疫学 免疫学 免疫学
背景情况:
- SARS-CoV-2 (严重急性呼吸系统综合征冠状病毒2) 的持续性挑战了疫苗和治疗疗效.
- 病毒进化是目前医疗对策效率降低的一个关键因素.
- 之前的研究表明,连续感染可以使病毒适应新宿主.
研究的目的:
- 为了调查K18-ACE2小鼠中传递SARS-CoV-2系 (Beta和Delta) 是否会推动人类健康相关的进化.
- 为了确定病毒进化是否依赖于特定的血统.
- 识别特定突变及其表型后果.
主要方法:
- 在K18-ACE2小鼠中连续传递未经修改的B.1.351 (Beta) 和B.1.617.2 (Delta) SARS-CoV-2菌株,超过20个通道.
- 在没有施加选择性压力的情况下,在BSL-3实验室环境中感染小鼠.
- 在生物体和肺组织水平上分析疾病严重程度.
- 纳米孔测序以识别突变,包括尖端蛋白的变化.
- 对抗体耐药性和干扰素抑制的评估.
主要成果:
- 与早期传递菌株相比,晚期传递病毒的传染性和死亡率增加.
- 晚期通道的三角体表现出显著的抗体耐药性和干扰素抑制.
- 一个新的尖端S371F突变被确定并与抗体耐药性和干扰素抑制有关.
- 奥米克朗的特征S371F突变有时与E1182G共同遗传.
- 两种S371F和E1182G突变都与哺乳动物GOLGA7和ZDHHC5的相互作用有关,影响病毒进入和宿主反应.
结论:
- SARS-CoV-2 呈现出具有显著表型后果的进化倾向.
- 病毒进化模式和结果因特定的血统而异.
- 这项研究表明非主导准物种在病毒进化中的贡献.
- 鉴定的突变及其相关途径为病毒适应和潜在的治疗点提供了洞察力.
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