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干扰素刺激的基因GALNT2限制了呼吸道病毒感染

Wei Ran^1,2, Jinghong Yang¹, Shi Yu²

¹The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China.

Nature microbiology

|December 12, 2025

概括

天生的免疫系统使用O-GalNAc转移酶2 (GALNT2) 来对抗像SARS-CoV-2这样的病毒. 这种抗病毒基因限制病毒复制,有助于清除,并减少疾病严重程度,与住院风险相关的变异.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
遗传学遗传学是一个

背景情况:

天生的免疫反应依赖于干扰素 (IFN) 和IFN刺激基因 (ISG) 来对抗病毒感染.
许多ISG具有未知的功能,突出显示了对抗病毒机制理解的差距.

研究的目的:

确定涉及与生俱来的免疫反应对SARS-CoV-2的新型抗病毒ISG.
阐明已识别的基因限制病毒复制并影响疾病严重性的机制.

主要方法:

感染SARS-CoV-2的小鼠肺部的转录形状分析.
来自COVID-19患者的支气管洗液和PBMCs的单细胞RNA测序.
在体外和体内实验,以评估已识别的基因的抗病毒活性.

主要成果:

O-GalNAc转移酶2 (GALNT2) 被确定为一种抗病毒ISG,可以限制多个冠状病毒和流感A病毒的复制.
病毒尖端蛋白的GALNT2依赖的O-链糖化可能会通过影响蛋白质分解处理和病毒细胞融合而损害病毒生长.
病毒尖端蛋白上的特定血清残留物 (810/813) 是GALNT2敏感性的关键决定因素.
人类遗传分析将GALNT2变种的抗病毒功能降低与SARS-CoV-2住院的风险增加联系起来.

结论:

GALNT2是一种关键的抗病毒因子,限制呼吸道病毒感染,包括SARS-CoV-2.
了解GALNT2的机制可以了解宿主-病原体相互作用和潜在的治疗点.
在GALNT2的遗传变异影响易感性严重的呼吸道病毒病.

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