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蝙蝠纤维细胞与SARS-CoV-2的流产性感染

Punam Bisht¹, Michael D Gallagher¹, M Inmaculada Barrasa¹

¹Whitehead Institute for Biomedical Research, Cambridge, MA 02142.

Proceedings of the National Academy of Sciences of the United States of America

|October 14, 2024

概括

蝙蝠对像SARS-CoV-2这样的病毒表现出了显著的耐受性. 受感染的蝙蝠细胞,与人类细胞不同,产生显著较少的传染性病毒,表明强大的先天免疫反应限制病毒复制.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
细胞生物学细胞生物学

背景情况:

蝙蝠对严重的病毒感染具有自然耐受性,包括埃博拉病毒和尼帕病毒.
严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 利用血管素转化酶2 (ACE2) 受体进入细胞.
了解蝙蝠对SARS-CoV-2的免疫反应,可以揭示病毒耐受性的机制.

研究的目的:

为了比较人类和蝙蝠细胞中的SARS-CoV-2感染动态.
研究ACE2受体在蝙蝠细胞对SARS-CoV-2敏感性的作用.
为了确定蝙蝠病毒耐受性的基础细胞机制.

主要方法:

人类ACE2 (hA) 受体转化为蝙蝠多能干细胞 (iPSC) 和纤维细胞.
转化的人类和蝙蝠细胞感染SARS-CoV-2.
传染性病毒产量和毒性的量化.
病毒RNA和蛋白质合成的分析.
电子显微镜检测类似病毒的粒子.

主要成果:

设计以表达HA的蝙蝠细胞易受SARS-CoV-2感染.
受感染的蝙蝠iPSCs-hA产生病毒的感染率低100倍,毒性低于人类胚胎干细胞-hA.
受感染的蝙蝠纤维细胞-hA合成了病毒RNA和蛋白质,但没有产生传染性病毒,表明了流产性感染.
电子显微镜证实了感染蝙蝠纤维细胞中没有类似病毒的颗粒.

结论:

蝙蝠体细胞,特别是纤维细胞,具有有效的机制来控制SARS-CoV-2的复制,导致流产性感染.
与人类细胞相比,蝙蝠多能干细胞显示病毒复制和毒性降低.
蝙蝠细胞中具有构成性激活的先天免疫系统可能有助于限制SARS-CoV-2感染.

关键词:

这就是SARS-CoV-2病毒.流产性感染是一种流产性感染.蝙蝠细胞是蝙蝠细胞中的一个.天生的免疫系统天生的免疫系统.

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