Influenza A viruses have frequently crossed species barriers and continually pose a threat to the health of birds, mammals, and humans. Highly pathogenic avian influenza virus (HPAIV), distinguished from low pathogenic avian influenza virus (LPAIV) by polybasic hemagglutinin (HA) cleavage site, extensively spread among wild birds and poultry since its initial discovery in Guangdong, China, in 1996 (A/goose/Guangdong/1/1996; Gs/GD) [1]. Numerous mutations have accumulated in the HA gene since the emergence of the Gs/GD lineage, further dividing HPAI into various clades, among which the HPAI H5N1 clade 2.3.4.4b emerged as the predominant strain on a global scale in 2020. Subsequently, HPAI H5N1 clade 2.3.4.4b was further classified into diverse genotypes via genetic reassortment among avian influenza viruses (AIVs) for eight gene segments. Genotypes of H5N1 clade 2.3.4.4b were classified as G1-G16 from Chinese avian isolates in 2021–2022. The South Korean avian isolates reported in November 2022 were classified into South Korea genotypes I and II, both of which were derived from the G10 genotype.

However, a striking paradigm shift in the global epidemiology of HPAI H5N1 clade 2.3.4.4b emerged during the winter of 2021–2022. Interspecies transmission of HPAIVs has been increased, in addition to conventional infections in poultry and wild bird populations. These cross-species transmissions have affected over 43 mammalian species spanning Europe, North America, South America, and Asia. Besides these instances in wild mammals, it was also reported in cats in France, the United States, Italy, and Poland between 2022 and 2023. In June and July 2023, feline AIV infections, confirmed to be caused by H5N1, occurred at two different shelters in Seoul, South Korea, with no confirmed human cases involved. The source of infection in the first case remains unclear; in the second case, the infection originated from infected poultry feed. This was the first case of mammalian infections caused by HPAI H5N1 in South Korea. This study covers the first case, whereas the second case is currently being analysed by the Ministry of Agriculture, Food and Rural Affairs. We describe the potential origin and genetic characteristics of HPAI H5N1 viruses from cats based on whole genome sequencing and phylogenetic analysis.