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

**Authors:** Dong-Hyun Son, Anand Balupuri, Jeong-Hyun Nam, Il-Hwan Kim, Yong Jun Choi, Bo Min An, Jeong-Min Kim, Eun-Jin Kim, Nam Sook Kang

PMC · DOI: 10.1080/21505594.2026.2636350 · 2026-02-23

## TL;DR

This study analyzed H5N1 avian flu viruses from cats in South Korea and found they still bind to bird-specific receptors, suggesting low risk for human transmission.

## Contribution

First experimental analysis of receptor binding specificity of feline-derived H5N1 viruses in South Korea.

## Key findings

- Feline-derived H5N1 viruses showed strong binding to avian-type α2,3-linked sialic acid receptors.
- No detectable binding to human-type α2,6-linked sialic acid receptors was observed in feline or avian isolates.
- Results indicate low potential for efficient human-to-human transmission of these H5N1 viruses.

## Abstract

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.

## Linked entities

- **Diseases:** influenza (MONDO:0005812), avian influenza (MONDO:0018695)

## Full-text entities

- **Genes:** KRT32 (keratin 32) [NCBI Gene 3882] {aka HA2, HKA2, KRTHA2, hHa2}, ESCO2 (establishment of sister chromatid cohesion N-acetyltransferase 2) [NCBI Gene 157570] {aka 2410004I17Rik, EFO2, EFO2p, JHS, RBS, hEFO2}, SLN (sarcolipin) [NCBI Gene 6588], IGKV6-21 (immunoglobulin kappa variable 6-21 (non-functional)) [NCBI Gene 28906] {aka A26, IGKV621}, IGKV2-24 (immunoglobulin kappa variable 2-24) [NCBI Gene 28923] {aka A23, IGKV224}
- **Diseases:** infectious disease (MESH:D003141), infection (MESH:D007239), HPAI (MESH:D005585)
- **Chemicals:** Hydrogen (MESH:D006859), PBS (MESH:D007854), N-acetylglucosamine (MESH:D000117), Cl- (MESH:D002713), Na+ (MESH:D012964), GalNAc (-), Gal (MESH:D005690), HCl (MESH:D006851), Oseltamivir acid (MESH:C535162), water (MESH:D014867), N-acetylneuraminic acid (MESH:D019158), Glycan (MESH:D011134), 3,3',5,5'-tetramethylbenzidine (MESH:C021758)
- **Species:** H5N1 subtype (serotype) [taxon 102793], Paratimomenus sp. DM09 (species) [taxon 307988], Homo sapiens (human, species) [taxon 9606], Viruses (acellular root) [taxon 10239], Hepatovirus A (no rank) [taxon 12092], Orthomyxoviridae (family) [taxon 11308], Anas platyrhynchos (duck, species) [taxon 8839], H1N1 subtype (serotype) [taxon 114727], Meleagris gallopavo (common turkey, species) [taxon 9103]
- **Mutations:** E227D, P141, Q169R, Q218, L269V, F95L, A133, M282V, K82R, N154D, Q223, K218Q, A83D, S223R, S181, R310K, V533M, G224S, Q115L, V174I, R212K, Q322L, S124N, G224, D45N, T133, R162I, V86A, V523A, K36T, K189N, T156A, I513T, S141P, N273H, A83N, R223, P181S, N240H, S123P, A127T, E224, S133A, A185E, N183, D222G, N72R, D488Y, S155D, K140A, D183N, Q192K, K329del, R53K, D94S, R325K, E268G, N236D

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940103/full.md

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Source: https://tomesphere.com/paper/PMC12940103