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炎症细胞死亡,PANoptosis,屏幕识别了冠状病毒先天免疫反应中的宿主因素,作为治疗点
R K Subbarao Malireddi1, Ratnakar R Bynigeri1, Raghvendra Mall1,2
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
这项研究使用了巨细胞的CRISPR查来识别冠状病毒感染和PANoptosis (一种炎症性细胞死亡形式) 所涉及的宿主因素. 发现这些因素可能会导致针对严重的冠状病毒疾病的新疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 遗传学 是一个遗传学.
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 引起了全球重大健康问题,对病毒进入和先天免疫反应的理解不完全.
- 天生的免疫反应,包括细胞因子风暴和细胞死亡,在贝塔冠状病毒 (β-CoV) 感染期间放大病理.
- 治疗策略需要对宿主-病原体相互作用和β-CoV感染中的先天免疫过程有更深入的了解.
研究的目的:
- 为了阐明宿主分子对β-CoV感染和巨细胞中的PANoptosis (炎症性细胞死亡) 至关重要.
- 开发和验证一种全基因组CRISPR-Cas9查方法,用于识别先天免疫中的宿主因素.
主要方法:
- 利用小鼠肝炎病毒 (MHV) 模型和巨细胞系中的全基因组CRISPR-Cas9屏幕.
- 进行全基因组查,以确定影响病毒进入和PANoptosis的宿主基因.
- 通过评估已识别的宿主因素的作用,包括已知的MHV受体Ceacam1.1,验证了这些发现.
主要成果:
- 屏幕成功识别了Ceacam1,MHV受体,作为病毒进入和随后细胞死亡的关键因素.
- 删除Ceacam1显著减少病毒复制和MHV诱导的巨细胞死亡.
- 确定了几种新型宿主因素,这些因素对MHV感染引起的巨细胞死亡至关重要.
结论:
- 在巨细胞中全基因组的PANoptosis幕是有效的发现宿主因素在先天免疫反应.
- 这些发现突出了使用这种查来加快对β-CoV诱导病理的治疗标的识别的可行性.
- 建议开发治疗方法的新途径,以减轻冠状病毒感染的严重后果.
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