Analyses of receptor binding specificity of highly pathogenic avian influenza A (H5N1) viruses isolated from felines in South Korea, 2023

Influenza viruses infect host cells by binding to specific sialic acid receptors present on the surface of target cells, and this receptor binding exhibits specificity depending on cell type and host species. Avian influenza A (H5N1) viruses typically bind preferentially to α2,3-linked sialic acid receptors, although some strains have been reported to acquire binding affinity for the human-type α2,6-linked sialic acid receptors, highlighting the need for ongoing receptor binding analyses of highly pathogenic avian influenza (HPAI) viruses. Notably, in July 2023, two distinct cases of fatal cluster infections in felines caused by HPAI H5N1 viruses were reported for the first time in South Korea (Gwanak and Yongsan). Characterization of the isolated strains revealed high pathogenicity and efficient contact transmission in mammals. In this study, we investigated the receptor binding specificity of the H5N1 viruses associated with these feline outbreaks to assess their potential threat to human health. Our findings demonstrated that both felines-derived and avian-derived H5N1 isolates retained strong binding affinity to avian-type α2,3-linked sialic acid receptors, while showing no detectable binding to human-type α2,6-linked sialic acid receptors. These results provide experimental evidence that the feline H5N1 isolates retain avian-type receptor specificity, indicating a low potential for efficient human-to-human transmission.