流感突变开关

IF 12.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature chemical biology Pub Date : 2025-01-23 DOI:10.1038/s41589-025-01839-x

Francesco Zamberlan

引用次数: 0

摘要

自2021年以来，高致病性H5N1流感分支2.3.4.4b病毒在北美的鸟类和牛中占主导地位，并导致了2024年德克萨斯州首例牛H5N1人感染病例（德克萨斯州H5）。尽管该病例引起了对病毒适应性的关注，但幸运的是，由于鸟类型血凝素（HA）识别具有α2,3连锁的唾液酸的细胞受体，而人类血凝素识别具有α2,6连锁的唾液酸，因此存在种间跳跃障碍。因此，受体结合偏好的转换被认为是人与人之间传播所必需的。现在，Lin等人在《科学》杂志上发表文章，证实了德克萨斯州H5中单一HA突变Gln226Leu的结合开关。研究小组首先利用表面等离子体共振、酶联免疫吸附试验和聚糖阵列分析，确定了野生型牛德克萨斯H5 HA、Gln226Leu突变体和其他H5流感病毒（携带多种突变）的聚糖结合。他们发现，Gln226Leu突变的引入将结合特异性从鸟类型转变为人类型，尽管结合常数较弱。先前在同一HA区域发现的其他突变增强了结合的亲和力，但不是结合α2,6键所必需的。接下来，研究人员用禽类受体类似物LSTa检测了牛Texas H5 HA的晶体结构；它与其他H5N1病毒类似地结合，Gln226与其聚糖形成氢键。获得Gln226Leu突变体与人受体类似物LSTc的晶体结构，表明该蛋白具有α2,6特异性，且Leu226与LSTc的非极性区发生范德华接触。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature chemical biology 生物-生化与分子生物学

CiteScore

23.90

自引率

1.40%

发文量

238

审稿时长

12 months

期刊介绍： Nature Chemical Biology stands as an esteemed international monthly journal, offering a prominent platform for the chemical biology community to showcase top-tier original research and commentary. Operating at the crossroads of chemistry, biology, and related disciplines, chemical biology utilizes scientific ideas and approaches to comprehend and manipulate biological systems with molecular precision. The journal embraces contributions from the growing community of chemical biologists, encompassing insights from chemists applying principles and tools to biological inquiries and biologists striving to comprehend and control molecular-level biological processes. We prioritize studies unveiling significant conceptual or practical advancements in areas where chemistry and biology intersect, emphasizing basic research, especially those reporting novel chemical or biological tools and offering profound molecular-level insights into underlying biological mechanisms. Nature Chemical Biology also welcomes manuscripts describing applied molecular studies at the chemistry-biology interface due to the broad utility of chemical biology approaches in manipulating or engineering biological systems. Irrespective of scientific focus, we actively seek submissions that creatively blend chemistry and biology, particularly those providing substantial conceptual or methodological breakthroughs with the potential to open innovative research avenues. The journal maintains a robust and impartial review process, emphasizing thorough chemical and biological characterization.