Pathogenicity and zoonotic potential of a novel pdm09-lineage H1N2 swine influenza A virus spatiotemporally linked to transboundary pig trade

International swine trade can disseminate influenza A viruses across borders, creating opportunities for reassortment with endemic swine viruses and the emergence of novel strains with zoonotic potential. Here, we characterize a novel H1N2 reassortant, A/swine/Korea/1030–3/2023 (1030–3), detected in South Korea and spatiotemporally associated with European swine lineages and international pig movement. 1030–3 harbors seven gene segments (PB2, PB1, PA, HA, NP, M and NS) closely related to a recent Danish zoonotic H1N1 virus of the 2009 pandemic (pdm09) lineage, and an N2 segment derived from an endemic Korean HxN2. In vitro assays demonstrated that 1030–3 preferentially bound human-type α2,6-linked sialic acid receptors and replicated efficiently in polarized human airway epithelial cells, although these properties were also observed in the endemic Korean H1N2 comparator 1027–1. In mice, 1030–3 caused moderate clinical signs and respiratory replication comparable to an early pdm09 reference strain NL09. In guinea pigs, 1030–3 transmitted to a subset of direct-contact animals but showed no detectable aerosol transmission under the conditions tested. In pigs, the natural host, 1030–3 replicated efficiently and transmitted to all direct-contact animals, with high respiratory shedding and a greater cumulative shedding burden in contact pigs than NL09. Contemporary human sera showed reduced neutralizing activity against 1030–3 relative to both human seasonal H1N1 and 1027–1, while antiserum against a recent H1N1 vaccine antigen also neutralized 1030–3 less efficiently. These findings identify a European-associated H1N2 swine influenza reassortant detected in South Korea that combines a distinct pdm09-derived genomic and antigenic background with efficient replication and transmission in pigs, α2,6-linked receptor preference, and reduced neutralization by human sera, underscoring the need for trade-aware surveillance of swIAVs and continued monitoring at the swine-human interface.