Lin Ting-Hui, Zhu Xueyong, Wang Shengyang, Zhang Ding, McBride Ryan, Yu Wenli, Babarinde Simeon, Paulson James C, Wilson Ian A
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Science. 2024 Dec 6;386(6726):1128-1134. doi: 10.1126/science.adt0180. Epub 2024 Dec 5.
In 2024, several human infections with highly pathogenic clade 2.3.4.4b bovine influenza H5N1 viruses in the United States raised concerns about their capability for bovine-to-human or even human-to-human transmission. In this study, analysis of the hemagglutinin (HA) from the first-reported human-infecting bovine H5N1 virus (A/Texas/37/2024, Texas) revealed avian-type receptor binding preference. Notably, a GlnLeu substitution switched Texas HA binding specificity to human-type receptors, which was enhanced when combined with an AsnLys mutation. Crystal structures of the Texas HA with avian receptor analog LSTa and its GlnLeu mutant with human receptor analog LSTc elucidated the structural basis for this preferential receptor recognition. These findings highlight the need for continuous surveillance of emerging mutations in avian and bovine clade 2.3.4.4b H5N1 viruses.
2024年，美国发生了几起人类感染高致病性2.3.4.4b分支牛流感H5N1病毒的事件，这引发了人们对该病毒从牛传播给人类甚至人际传播能力的担忧。在这项研究中，对首次报告的感染人类的牛H5N1病毒（A/德克萨斯/37/2024，德克萨斯）的血凝素（HA）进行分析，发现其具有禽型受体结合偏好。值得注意的是，一个GlnLeu替代将德克萨斯HA的结合特异性转变为人类型受体，当与一个AsnLys突变结合时，这种转变会增强。德克萨斯HA与禽受体类似物LSTa及其具有人类受体类似物LSTc的GlnLeu突变体的晶体结构阐明了这种优先受体识别的结构基础。这些发现凸显了对禽和牛2.3.4.4b分支H5N1病毒中出现的突变进行持续监测的必要性。
