Abstract
Clade 2.3.4.4b high pathogenicity avian influenza H5N1 viruses have caused an unprecedented panzootic. These H5N1 viruses have caused devastation not only in poultry farms and wild animal populations but also in dairy cattle and goat farms, affecting more than 387 dairy farms across fourteen USA states . The immunodominant haemagglutinin glycoprotein (HA) is crucial for the influenza virus’s receptor binding and pH-induced fusion with cellular membranes. Mutations in HA often lead to antigenic modulation and expansion of host range and tropism. We examined the HA genes from a comprehensive panel of clade 2.3.4.4b H5 viruses from prevalent genotypes during UK outbreaks spanning 2020 to 2022, as well as from cattle and goat outbreaks in the USA in 2024, focusing on receptor binding and pH fusion. All tested H5N1 viruses bound exclusively to avian-like receptors, with fusion pH values above 5.8, outside the pH range associated with efficient human airborne transmissibility (pH 5.0 to 5.5). We further investigated HA genes of clade 2.3.4.4b H5Nx viruses globally, focusing on less conserved amino acids within the receptor-binding domain. Through a rigorous approach, we identified specific amino acid residues that enhanced virus binding to human-type receptors. Following viral passage in the presence of homologous antisera, a mutation associated with human-type receptor binding was identified as an immune escape variant. This finding underscores the ongoing evolution of H5 viruses and their potential adaptation towards increased human infectivity, emphasizing the need for continued surveillance and a deeper understanding of viral dynamics to mitigate future zoonotic risks.
Co-Author(s)
Jiayun Yang1, Mehnaz Qureshi1, Rebecca Daines1, Thusitha Karunarathna1, Reddy Kolli1, Jean-Remy Sadeyen1, Thomas P. Peacock1,2, Joe James3,4, Marek J. Slomka3, Ashley Banyard3,4, Wendy S. Barclay2, Ian H. Brown1 and Munir Iqbal1
1The Pirbright Institute, Pirbright, Woking, United Kingdom
2Department of Infectious Disease, Imperial College London, London, United Kingdom.
3Virology Department, Animal and Plant Health Agency, Addlestone, Surrey, United Kingdom
4WOAH/FAO International Reference Laboratory for Avian Influenza, Swine Influenza and Newcastle Disease, Animal and Plant Health Agency (APHA-Weybridge), Addlestone, Surrey, United Kingdom
Abstract Category
Avian influenza in mammals, pandemic preparedness, and one health