在人性化的 hACE2金色仓鼠中,TMPRSS2对于致命的SARS-CoV-2 BA.5感染是不可或缺的
Bowen Wang1, Jinwei Zhang1, Yuhan Li2
1State Key Laboratory of Reproductive Medicine and Offspring Health, Jiangsu Animal Experimental Center of Medicine and Pharmacy, Animal Core Facility, Key Laboratory of Model Animal, Department of Cell Biology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing, China.
European journal of medical research
|January 24, 2026
概括
黄金仓鼠的TMPRSS2缺陷降低了SARS-CoV-2的易感性,降低了病毒载量和肺部损伤. 然而,在人性化的ACE2仓鼠中,SARS-CoV-2的死亡率独立于TMPRSS2.2发生.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 病理学 病理学 病理学
背景情况:
- 严重急性呼吸道综合征冠状病毒 (SARS-CoV-2) 使用尖端 (S) 蛋白来结合血管酶转化酶2 (ACE2) 受体进入宿主细胞.
- 在呼吸道和其他组织中,ACE2的表达很高,这有助于SARS-CoV-2的传播.
- 跨膜血清蛋白酶2 (TMPRSS2) 切割SARS-CoV-2尖端蛋白,激活病毒进入并增强ACE2结合.
研究的目的:
- 调查TMPRSS2在SARS-CoV-2感染和易感性中的作用.
- 评估TMPRSS2缺陷对黄金仓鼠模型中的病毒载量和病理损伤的影响.
- 为了确定TMPRSS2是否对SARS-CoV-2诱导的人类化ACE2子的死亡率至关重要.
主要方法:
- 使用三个SARS-CoV-2变种 (Beta,BA.5,XBB) 在野生型和TMPRSS2淘汰赛 (KO) 金色仓鼠中的感染实验.
- 肺部病毒标位和病理损伤的评估.
- 在TMPRSS2 KO;H11-K18-hACE2仓鼠和H11-K18-hACE2仓鼠之间的死亡率的比较.
主要成果:
- 黄金仓鼠的TMPRSS2缺乏导致肺部病毒标位显著降低,病理损伤减少,与野生类型对照相比.
- 感染SARS-CoV-2 BA.5菌株导致Tmprss2 KO;H11-K18-hACE2仓鼠在注射后5天死亡,类似于H11-K18-hACE2仓鼠.
- 这些发现表明,虽然TMPRSS2影响病毒载量和病理学,但在这个人性化的模型中,它对SARS-CoV-2引起的死亡率并不重要.
结论:
- 在黄金仓鼠中,TMPRSS2在调节SARS-CoV-2易感性,病毒复制和相关的肺病理学方面发挥着作用.
- 在人性化的ACE2仓鼠中,SARS-CoV-2诱导的死亡率独立于TMPRSS2活动.
- 向TMPRSS2可能通过减少病毒载量和疾病严重程度来提供治疗益处,但其他途径有助于致命的结果.
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