A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors.

Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE

Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-

Hemagglutinin Glycoproteins, Influenza Virus*/chemistry ; Hemagglutinin Glycoproteins, Influenza Virus*/genetics ; Hemagglutinin Glycoproteins, Influenza Virus*/metabolism ; Influenza A Virus, H5N1 Subtype*/genetics ; Influenza, Human*/virology ; Orthomyxoviridae Infections*/transmission ; Orthomyxoviridae Infections*/veterinary ; Orthomyxoviridae Infections*/virology ; Receptors, Virus*/metabolism ; Receptors, Virus*/genetics ; Receptors, Virus*/chemistry; Animals ; Cattle ; Humans ; Amino Acid Substitution ; Crystallography, X-Ray ; Mutation

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 Gln ²²⁶ Leu substitution switched Texas HA binding specificity to human-type receptors, which was enhanced when combined with an Asn ²²⁴ Lys mutation. Crystal structures of the Texas HA with avian receptor analog LSTa and its Gln ²²⁶ Leu 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.

0 (Hemagglutinin Glycoproteins, Influenza Virus)
0 (Receptors, Virus)

Date Created: 20241205 Date Completed: 20241205 Latest Revision: 20241206

20241209

10.1126/science.adt0180

39636969