Location: Virus and Prion ResearchTitle: Changes in the hemagglutinin and internal gene segments were needed for human seasonal H3 influenza A virus to efficiently infect and replicate in swine
|RAJAO, DANIELA - University Of Georgia
|POWELL, JOSHUA - Oak Ridge Institute For Science And Education (ORISE)
|BOLTON, MARCUS - Oak Ridge Institute For Science And Education (ORISE)
|GAUGER, PHILLIP - Iowa State University
|SUTTON, TROY - Pennsylvania State University
|PEREZ, DANIEL - University Of Georgia
Submitted to: Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/20/2022
Publication Date: 8/25/2022
Citation: Rajao, D., Abente, E.J., Powell, J.D., Bolton, M.J., Gauger, P.C., Arruda, B.L., Anderson, T.K., Sutton, T., Perez, D.R., Baker, A.L. 2022. Changes in the hemagglutinin and internal gene segments were needed for human seasonal H3 influenza A virus to efficiently infect and replicate in swine. Pathogens. 11(9). Article 967. https://doi.org/10.3390/pathogens11090967.
Interpretive Summary: Interspecies transmission of influenza A viruses (IAV) from humans to pigs is relatively common and led to many human-origin influenza viruses becoming endemic in pigs. These human-to-swine spillover events significantly affected the epidemiology and the resulting diversity imposes a major challenge to disease prevention and control. Experimental infection of pigs with human IAV often results in low replication and rare transmission among pigs. Little is known about the evolutionary processes that occur at the human-swine interface that allow human seasonal viruses to adapt and efficiently replicate and transmit within the new host. Novel human-like H3 viruses were detected in swine herds in the U.S. in 2012 and continue to circulate and evolve in swine. The objective of this study was to evaluate the contributions of gene segments on the ability of human origin H3 viruses to infect pigs by using a series of in vitro models. We showed that the adaptation of human seasonal H3 viruses to swine involved multiple IAV gene segments and the hemagglutinin gene alone was not sufficient to restore properties of the wild-type swine-adapted virus. Understanding these mechanisms of IAV adaptation to swine will allow for more rapid identification of human viruses that have the potential to become established in pigs.
Technical Abstract: The current diversity of influenza A viruses (IAV) circulating in swine is largely a consequence of human-to-swine transmission events and consequent evolution in pigs. However, little is known about the requirements for human IAVs to transmit to and subsequently adapt in pigs. Novel human-like H3 viruses were detected in swine herds in the U.S. in 2012 and have continued to circulate and evolve in swine. We evaluated the contributions of gene segments on the ability of these viruses to infect pigs by using a series of in vitro models. For this purpose, reassortant viruses were generated by reverse genetics (rg) swapping the surface genes (hemagglutinin-HA and neuraminidase-NA) and internal gene segment backbones between a human-like H3N1 isolated from swine and a seasonal human H3N2 virus with common HA ancestry. Virus growth kinetics in porcine intestinal epithelial cells (SD-PJEC) and in ex-vivo porcine trachea explants were significantly reduced by replacing the swine-adapted HA with the human seasonal HA. Unlike the human HA, the swine-adapted HA demonstrated more abundant attachment to epithelial cells throughout the swine respiratory tract by virus histochemistry and increased entry into SD-PJEC swine cells. The human seasonal internal gene segments improved replication of the swine-adapted HA at 33°C, but decreased replication at 40°C. Although the HA was crucial for the infectivity in pigs and swine tissues, these results suggest that the adaptation of human seasonal H3 viruses to swine is multigenic and that the swine-adapted HA alone was not sufficient to confer the full phenotype of the wild-type swine-adapted virus.