Shiloh
Editor, Senior Moderator
Source: https://www.science.org/doi/10.1126/science.adt0180
A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors
Ting-Hui Lin https://orcid.org/0000-0002-0937-9972, Xueyong Zhu https://orcid.org/0000-0002-6021-3740, Shengyang Wang https://orcid.org/0000-0002-8454-1255, Ding Zhang https://orcid.org/0009-0001-1057-0256, Ryan McBride https://orcid.org/0000-0001-8616-1910, Wenli Yu https://orcid.org/0000-0002-4025-2646, Simeon Babarinde https://orcid.org/0000-0001-5603-4769, James C. Paulson https://orcid.org/0000-0003-4589-5322 , and Ian A. Wilson https://orcid.org/0000-0002-6469-2419 Authors Info & Affiliations
Science
5 Dec 2024
Vol 386, Issue 6726
pp. 1128-1134
Editor’s summary
In 2021, a highly pathogenic influenza H5N1 clade 2.3.4.4b virus was detected in North America that is capable of infecting a diversity of avian species, marine mammals, and humans. In 2024, clade 2.3.4.4b virus spread widely in dairy cattle in the US, causing a few mild human cases, but retaining specificity for avian receptors. Historically, this virus has caused up to 30% fatality in humans, so Lin et al. performed a genetic and structural analysis of the mutations necessary to fully switch host receptor recognition. A single glutamic acid to leucine mutation at residue 226 of the virus hemagglutinin was sufficient to enact the change from avian to human specificity. In nature, the occurrence of this single mutation could be an indicator of human pandemic risk. —Caroline Ash
Abstract
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 Gln226Leu substitution switched Texas HA binding specificity to human-type receptors, which was enhanced when combined with an Asn224Lys mutation. Crystal structures of the Texas HA with avian receptor analog LSTa and its Gln226Leu 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.
A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors
Ting-Hui Lin https://orcid.org/0000-0002-0937-9972, Xueyong Zhu https://orcid.org/0000-0002-6021-3740, Shengyang Wang https://orcid.org/0000-0002-8454-1255, Ding Zhang https://orcid.org/0009-0001-1057-0256, Ryan McBride https://orcid.org/0000-0001-8616-1910, Wenli Yu https://orcid.org/0000-0002-4025-2646, Simeon Babarinde https://orcid.org/0000-0001-5603-4769, James C. Paulson https://orcid.org/0000-0003-4589-5322 , and Ian A. Wilson https://orcid.org/0000-0002-6469-2419 Authors Info & Affiliations
Science
5 Dec 2024
Vol 386, Issue 6726
pp. 1128-1134
Editor’s summary
In 2021, a highly pathogenic influenza H5N1 clade 2.3.4.4b virus was detected in North America that is capable of infecting a diversity of avian species, marine mammals, and humans. In 2024, clade 2.3.4.4b virus spread widely in dairy cattle in the US, causing a few mild human cases, but retaining specificity for avian receptors. Historically, this virus has caused up to 30% fatality in humans, so Lin et al. performed a genetic and structural analysis of the mutations necessary to fully switch host receptor recognition. A single glutamic acid to leucine mutation at residue 226 of the virus hemagglutinin was sufficient to enact the change from avian to human specificity. In nature, the occurrence of this single mutation could be an indicator of human pandemic risk. —Caroline Ash
Abstract
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 Gln226Leu substitution switched Texas HA binding specificity to human-type receptors, which was enhanced when combined with an Asn224Lys mutation. Crystal structures of the Texas HA with avian receptor analog LSTa and its Gln226Leu 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.