Transmission and Pathologic Findings of Divergent Human Seasonal H1N1pdm09 Influenza A Viruses Following Spillover Into Pigs in the United States.

The H1N1 pandemic (H1N1pdm09) lineage of influenza A viruses (IAV) emerged in North America in 2009. It spread rapidly due to efficient transmission and the limited immunity in humans, replacing the previous human seasonal H1. Human-to-swine transmission of H1N1pdm09 IAV has since contributed to genetic diversity in pigs. While most were not sustained, approximately 160 spillovers persisted in pigs in the United States for at least 1 year and reassorted with other endemic swine IAVs in most cases. We sought to identify how transmission and reassortment with endemic IAV in swine impact virus traits and zoonotic risk in this study. We conducted a swine pathogenesis and transmission study using four swine H1N1pdm09 viruses derived from different human influenza seasons that had acquired different gene segment combinations after spillovers into swine. To assess antigenic evolution, we compared the selected swine H1N1pdm09 strains against each other and to five human seasonal H1 vaccine strains. Ongoing circulation and reassortment resulted in viruses with variable virulence, shedding, and transmission kinetics. The H1N1pdm09 viruses retained antigenic similarities with the human vaccine strain of the same season of incursion but showed increasing antigenic distances with human seasonal H1N1 vaccine strains from other seasons. Human seasonal H1N1 viruses are capable of replicating and transmitting in swine, and there is potential for these human-to-swine spillovers to reassort with endemic swine IAV. Controlling IAV at the human-swine interface has the benefit of reducing IAV burden in swine and subsequent zoonotic risk.