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

Abstract

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.