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

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…

• UD
  U.S. Department of Energy

  Awards: 76SF00515, SC0012704, DE-AC02, AC02-76SF00515, P30GM133894, DE-AC02-
• UO
  University of Pennsylvania
• NI
  National Institutes of Health

  Awards: P30GM133894, 75N93021C00015, DE-AC02-76SF00515
• OO
  Office of Science

  Awards: AC02-76SF00515, DE-AC02-76SF00515, DE-AC02, SC0012704, 76SF00515, DE-SC0012704
• NI
  National Institute of General Medical Sciences

  Awards: 17-ID-2, P30GM133894, DE-AC02-76SF00515
• NI
  National Institute of Allergy and Infectious Diseases

  Award: 75N93021C00015
• BE
  Basic Energy Sciences

  Awards: DE-AC02, DE-SC0012704, DE-AC02-76SF00515, 76SF00515, SC0012704, AC02-76SF00515
• BA
  Biological and Environmental Research

  Awards: DE-SC0012704, DE-AC02-76SF00515, P30GM133894
• BN
  Brookhaven National Laboratory

  Award: SC0012704
• SN
  SLAC National Accelerator Laboratory

  Awards: AC02-76SF00515, DE-AC02-76SF00515