在人性化模型动物中感染各种SARS-CoV-2变种引起的肺损伤的病态形态特征
A S Chernov1, V A Kazakov1, I S Gogleva1
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian Federation.
Doklady. Biochemistry and biophysics
|February 4, 2026
概括
新的SARS-CoV-2变种存在风险. 在人性化的小鼠中,Delta变种比武汉或Omicron菌株更严重地造成肺损伤和死亡率,突出显示了其增加的毒性.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 病理学 病理学 病理学
背景情况:
- SARS-CoV-2 呈现出高度的遗传变异性,导致具有增加毒性和免疫逃避潜力的新菌株.
- 了解新出现的SARS-CoV-2变种的病原性对于开发有效的对策至关重要.
- 实验性动物模型对于研究病毒病原和评估治疗策略至关重要.
研究的目的:
- 使用人性化的小鼠模型研究不同SARS-CoV-2变异的病原性.
- 为了比较武汉,三角洲和Omicron变种在易感宿主中引起的毒性和疾病严重程度.
- 为了确定SARS-CoV-2变种之间病理结果的潜在差异.
主要方法:
- 使用了一个人性化的小鼠模型 (表达 hACE2 的C57BL/6-Tgtn线).
- 在不同剂量中以三种SARS-CoV-2变种 (武汉,三角洲,奥米克朗) 感染鼻腔小鼠.
- 评估了肺组织的病理变化,确定了死亡率.
主要成果:
- 被所有三种SARS-CoV-2变种感染的人类化的 hACE2小鼠表现出与人类COVID-19一致的肺病理.
- 4个日志斑块形成单位 (PFU) 的剂量导致所有测试变体的100%死亡率.
- 在这个模型中,与武汉和Omicron变种相比,Delta变种引发的肺损伤明显更严重.
结论:
- 人性化的 hACE2小鼠模型有效地复制了SARS-CoV-2引起的肺病理.
- 在这个实验系统中,Delta变种表现出比武汉和Omicron变种更高的毒性和病原性.
- 这种模型对SARS-CoV-2变种病原体的比较研究以及对抗病毒策略的临床前评估非常有价值.
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