转基因 hACE2-汉姆斯特创始人系中对SARS-CoV-2感染的易感性差异
Scott A Gibson1,2, Yanan Liu1, Rong Li1
1Department of Animal, Diary and Veterinary Sciences, Utah State University, Logan, UT 84322, USA.
Viruses
|October 26, 2024
概括
转基因仓鼠表达人类血管酶转化酶2 (hACE2) 提供了严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 模型. 用聚诺西尼克-聚乙烯酸 (Poly (I:C)) 预防性治疗改善了高度敏感的HACE2转基因仓鼠的存活率.
科学领域:
- 病毒学 病毒学
- 遗传学 是一个遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- 金色的叙利亚仓鼠易受SARS-CoV-2的感染,但表现出有限的疾病.
- 对于COVID-19的病原和治疗开发,需要一种更严重的动物模型.
- 人体 ангиотензин转化酶2 (hACE2) 是SARS-CoV-2进入的主要受体.
研究的目的:
- 开发和描述一个严重的COVID-19动物模型,使用HACE2转基因仓鼠.
- 评估不同HACE2转基因仓鼠创始人系的易感性和疾病进展情况.
- 在本模型中评估聚诺辛酸-聚乙烯酸 (Poly (I:C)) 的治疗潜力.
主要方法:
- 转基因哈姆斯特HaaCE2创始人线的产生.
- 创始人系感染SARS-CoV-2并监测临床症状,体重减轻和死亡率.
- 组织中的病毒载量量化和对其组织病理变化的评估.
- 在高度敏感的线条中用Poly (I:C) 进行预防性治疗.
主要成果:
- 高度敏感的HACE2转基因仓鼠系 (F0F35,F0M41) 在感染后6天内迅速发展为严重疾病,包括死亡.
- 临床症状包括昏迷,体重减轻,呼吸不全,以及鼻炎,肺炎和脑炎的组织病理证据.
- 预防性Poly (I:C) 治疗显著改善了高度敏感的HACE2子的存活率.
结论:
- hACE2转基因仓鼠为研究严重的SARS-CoV-2感染和COVID-19病原体提供了有价值的模型.
- 创始人系的变异影响了对致命的SARS-CoV-2感染的易感性.
- 在这种严重的COVID-19仓鼠模型中,Poly (I:C) 证明了保护效果.
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