一种常见的HLA基因与无症状的SARS-CoV-2感染有关
Danillo G Augusto1,2,3, Lawton D Murdolo4, Demetra S M Chatzileontiadou4,5
1Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA.
Nature
|July 19, 2023
概括
一种特定的人类白细胞抗原 (HLA) 基因变异,HLA-B*15:01,与无症状的SARS-CoV-2感染密切相关. 这是由于与季节性冠状病毒交叉反应的T细胞免疫力.
科学领域:
- 免疫学
- 遗传学
- 病毒学
背景情况:
- 超过20%的SARS-CoV-2感染无症状.
- 无症状感染为早期免疫反应和病毒清除提供了洞察力.
- 人类白细胞抗原 (HLA) 的变异可能影响无症状的SARS-CoV-2感染.
研究的目的:
- 调查HLA位置变异与无症状SARS-CoV-2感染之间的关联.
- 探索由HLA变体介导的无症状感染的免疫机制.
主要方法:
- 基于智能手机的研究追踪了29947人的COVID-19症状和结果.
- 对参与者进行高分辨率的HLA基因型鉴定.
- 在未接种疫苗的人群中,HLA位点与疾病过程的关联测试呈阳性SARS-CoV-2测试结果.
- 在特定HLA类型的个体中对SARS-CoV-2的疫情前T细胞反应性的分析.
- 对HLA复合物的结构分析.
主要成果:
- 在两个群体中发现HLA-B*15:01和无症状的SARS-CoV-2感染之间存在显著的关联.
- 来自HLA-B*15:01载体的流行前样本的T细胞对SARS-CoV-2具有反应性.
- 这些T细胞表现出记忆表型,多功能性和对季节性冠状病毒的交叉反应性.
- 结构分析证实了HLA-B*15:01对SARS-CoV-2和季节性冠状病毒的类似呈现.
结论:
- HLA-B*15:01与无症状的SARS-CoV-2感染有很强的联系.
- 由于对季节性冠状病毒的交叉反应,先前存在的T细胞免疫提供了这种关联的分子基础.
- 这一发现突显了HLA基因在调节COVID-19疾病过程中的作用.
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