欧洲分子生物学实验室的研究人员绘制了详细的分子图谱,揭示了流感A病毒如何劫持人类细胞并利用其进行复制[1]。研究发现病毒通过两种关键策略控制宿主细胞:血凝素蛋白在细胞内运输网络中获得宿主蛋白帮助,同时病毒导致细胞核内的副斑点结构溶解并释放RNA结合蛋白供自身复制使用[1]。该发现已发表在《自然微生物学》杂志上[1]。
研究采用了定制的交联质量分析法在完整感染细胞内直接观察蛋白质相互作用,并结合改进的AlphaFold算法进行结构建模[1]。这是首次在大规模范围内在完整感染细胞内绘制流感蛋白与人类蛋白的直接接触[1]。研究人员在所有测试的细胞系和流感株中均观察到副斑点结构的一致溶解[1]。季节性流感每年导致全球300-500万例重症病例,与65万例死亡有关[1]。研究人员认为该方法最终可应用于H5N1等具有大流行潜力的病毒[1]。
Researchers from the European Molecular Biology Laboratory have created a detailed molecular map showing how influenza A virus commandeers human cells for replication.[1] The study employed a custom cross-linking mass spectrometry technique to directly observe protein interactions within intact infected cells, combined with enhanced AlphaFold modeling for structural analysis.[1] This represents the first large-scale mapping of direct contact points between flu proteins and human proteins conducted within complete infected cells.[1]
The research identified two key viral strategies for cellular control: the hemagglutinin protein receives assistance from host proteins in the cell's transport network, and the virus causes the dissolution of subnuclear structures called nuclear speckles, releasing RNA-binding proteins that the virus then exploits for its own replication.[1] The speckle dissolution was observed consistently across all tested cell lines and flu strains examined in the study.[1]
Seasonal influenza causes between three to five million severe cases annually worldwide, associated with approximately 650,000 deaths.[1] Scientists believe this methodological approach could eventually be applied to pandemic-potential viruses such as H5N1.[1] The findings were published in Nature Microbiology.[1]