广泛的基因环境相互作用塑造了住院COVID-19患者对SARS-CoV-2感染的免疫反应
Haley E Randolph1,2, Raúl Aguirre-Gamboa3, Elsa Brunet-Ratnasingham4
1Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
bioRxiv : the preprint server for biology
|December 16, 2024
概括
遗传因素影响COVID-19反应,在急性感染中具有明显的基因调节. 环境因素显著改变了对SARS-CoV-2的免疫反应,影响了基因表达.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 计算生物学 计算生物学
背景情况:
- 全基因组关联研究 (GWAS) 确定了与COVID-19易感性和严重性相关的遗传位置.
- 在SARS-CoV-2感染异质性和临床结果中cis-regulatory遗传因素的作用尚未完全理解.
研究的目的:
- 在急性和康复性COVID-19期间调查免疫细胞的cis-regulatory遗传变异.
- 在对SARS-CoV-2感染的反应中识别细胞类型特定的遗传效应和基因环境相互作用.
主要方法:
- 来自COVID-19患者和健康对照的外周血液单核细胞 (PBMC) 的单细胞RNA测序 (scRNA-seq).
- 表达量性特征位点 (eQTL) 在多种免疫细胞类型和疾病状态中进行映射.
- 对细胞状态和基因型相互作用以及基因与环境相互作用的分析.
主要成果:
- 数以千计的cis相关变异被确定,在急性COVID-19中,数百个是免疫细胞独有的.
- 患者特异性遗传效应在感染解决过程中减少,这表明了动态的调节网络.
- 在干扰素反应等途径中观察到显著的细胞状态基因型相互作用,特别是在CD14+单细胞中.
- 大约25.6%的基因显示基因与环境的相互作用,突出显示了环境对免疫反应调节的影响.
结论:
- 在急性SARS-CoV-2感染期间,不同的基因调节网络是活跃的.
- 环境因素在调节对COVID-19免疫反应的转录调节方面发挥着至关重要的作用.
- 研究相关细胞类型和疾病背景中的调控变异对于理解宿主对感染的反应至关重要.
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