The Q226L mutation can convert a highly pathogenic H5 2.3.4.4e virus to bind human-type receptors

• 成果类型: Article
• 署名作者: Carrasco, Maria Rios; Lin, Ting-Hui; Zhu, Xueyong; Garcia, Alba Gabarroca; Uslu, Elif; Liang, Ruonan; Spruit, Cindy M.; Richard, Mathilde; Boons, Geert-Jan; Wilson, Ian A.; de Vries, Robert P.
• 署名单位: Utrecht University; Scripps Research Institute; Erasmus University Rotterdam; Erasmus MC; University System of Georgia; University of Georgia; Scripps Research Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10130
• DOI: 10.1073/pnas.2419800122
• 发表日期: 2025-04-22
• 关键词: avian influenza-virus; hemagglutinin; specificity; ACID; transmission; adaptation; EVOLUTION; virulence; residues

摘要

H5Nx viruses continue to wreak havoc in avian and mammalian species worldwide. The virus distinguishes itself by the ability to replicate to high titers and transmit efficiently in a wide variety of hosts in diverse climatic environments. Fortunately, transmission to and between humans is scarce. Yet, if such an event were to occur, it could spark a pandemic as humans are immunologically na & iuml;ve to H5 viruses. A significant determinant of transmission to and between humans is the ability of the influenza A virus hemagglutinin (HA) protein to shift from an avian-type to a human-type receptor specificity. Here, we demonstrate that a 2016 2.3.4.4e virus HA can convert to human-type receptor binding via a single Q226L mutation, in contrast to a cleavage-modified 2016 2.3.4.4b virus HA. Using glycan arrays, X-ray structural analyses, tissue-and direct glycan binding, we show that L133a Delta and 227Q are vital for this phenotype. Thus, whereas the 2.3.4.4e virus HA only needs a single amino acid mutation, the modified 2016 2.3.4.4b HA was not easily converted to human-type receptor specificity.