Major Shift of Influenza A Virus of Swine (IAV-S) by Human-to-Swine Spillover of the 2009 Pandemic Virus in Korea

The 2009 influenza A H1N1 pandemic (pdm09) originated from the influenza A virus of swine (IAV-S) through multiple reassortment events with avian and human IAVs. The pdm09 reportedly reintroduced the virus to pigs, contributing to the evolution and diversity of IAV-S through frequent reassortment and drifts. Surveillance and whole-genome sequencing of IAV-S from conventional pig farms in Korea during 2021-2022 revealed that the genetic diversity of H1 and H3 IAV-S was continuously enriched after human-to-swine spillover of pdm09 viruses with long-term maintenance, persistence, and reassortment of virus lineages. Evidence of additional human-to-swine spillover of viruses that are different from the 2009 virus but close to that of the recent H1N1pdm09 human vaccine was identified in this study. The identification of swine-adapted pdm09 viruses, which have accumulated amino acid mutations with potentially altered antigenicity and a unique potential N-glycosylation site within the haemagglutinin (HA) gene, suggests the distinctive evolution of spillover pdm09 viruses in swine. The genetic constellation of the recently emerging Eurasian avian-like swine lineage and the preexisting classical swine lineage H1 viruses in Korea has been expanded through reassortment with cocirculating pdm09 viruses and/or H3N2 IAV-S harboring the pdm09 M gene (H3N2pM). Collectively, after the major shift of Korean IAV-S from the classical swine lineage to the pdm09 lineage in 2009, the frequent spillover of pdm09 viruses and the circulation of IAV-S harboring pdm09 gene segments led to the continuous diversification of IAV-S through antigenic drift and shift, raising concerns about the potential reintroduction of these viruses to humans.