Transmission and pathology of divergent human seasonal H1N1pdm09 influenza A viruses following spillover into pigs in the United States

Authors: CIACCI ZANELLA, GIOVANA - Iowa State University; Markin, Alexey; SNYDER, CELESTE - Iowa State University; THOMAS, MEGAN - Iowa State University; Kunzler Souza, Carine; Arruda, Bailey; Anderson, Tavis; Baker, Amy

Submitted to: Influenza and Other Respiratory Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2025
Publication Date: N/A
Citation: N/A

Interpretive Summary: In 2009, an H1N1 influenza A virus (IAV) that originated in pigs caused a human pandemic. Since that time, this virus was repeatedly re-introduced back into pigs. These viruses then exchange genetic material with other swine IAV, increasing the diversity of circulating viruses. This viral diversity makes controlling influenza infection in the swine population with methods like vaccines very difficult. It also poses a risk to humans since these viruses likely keep their capability of infecting and transmitting from person to person. Our study explored how these human viruses evolve in the swine population and the risk of spreading back into humans. Using a pig-to-pig transmission study, we demonstrated that human viruses that circulated the longest in pigs without exchanging gene segments with swine IAV caused less disease. Strains that exchanged genetic material with other swine viruses transmitted quicker and more efficiently. We used antigenic characterization to study how the virus surface proteins changed in swine and demonstrated that the surface protein of these viruses lost antibody recognition over time. We also showed that antibodies recognizing current human H1N1 vaccine viruses do not recognize the swine viruses selected and studied here. These findings are indications of how well vaccines and immune responses will work against these swine viruses. Altogether, our data shows that continued circulation in the pig population allows these viruses to display distinct characteristics in the swine host and that they pose a risk to humans.

Technical Abstract: Background: The H1N1 pandemic (H1N1pdm09) lineage of influenza A viruses (IAV) emerged in North America in 2009 and developed into a human influenza pandemic. It spread rapidly due to its efficient transmission and limited human immunity, replacing the previous human seasonal H1. Human-to-swine transmission of H1N1pdm09 IAV has since contributed to genetic diversity in pigs. While most spillovers were not sustained, in ~160 instances human-origin viruses persisted in pigs for at least one year and, in most cases, reassorted with other endemic swine IAVs. Methods: In this study, we sought to identify how transmission and reassortment with endemic IAV viruses in swine impact virus traits and zoonotic risk. 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. Nasal swabs, serum, bronchoalveolar lavage fluid, and formalin-fixed lower respiratory tract tissues were collected to assess viral infection, replication, and shedding. Results: 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. Conclusions: Human H1N1pdm09 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 of swine IAV.