Zoonotic risk assessment of Swine Influenza A viruses

Background: Swine influenza is a highly contagious respiratory disease in pigs that can cause significant disease burden and substantial production and economic losses in the swine industry. The disease, caused by swine influenza A viruses (swIAV), is currently enzootic worldwide and affects millions of pigs yearly. Cross-species transmission has been well-documented for influenza A viruses, and swIAV is no exception, with the potential to cause severe consequences to both animal and human health. Pigs play an important role as "mixing vessels" for the generation of novel human pandemic influenza A viruses, meaning they can be infected by influenza A viruses from a variety of avian and mammalian species. As such, pigs play a crucial role in diversifying influenza A viruses and emerging new swIAV variants, some of which have zoonotic potential. However, despite the occurrence of multiple devastating influenza epidemics and pandemics in the past, our knowledge of the zoonotic potential of swIAV that circulate in pig populations in Europe is limited.Objectives and aims: Despite the recent increasing genomic surveillance efforts for swIAV across Europe, our current understanding of the viral determinants and biological characteristics influencing the zoonotic potential of swIAV is limited. In this project, we will leverage the genomic surveillance and phylogenetic analysis data of swIAV generated during the ESFLU COST Action to identify swIAV variants of interest (VOI) and (I) create a reverse genetic clone repository for swIAV that enables (II) comprehensive biological characterization and risk assessment of swIAV in biologically relevant in vitro models of the human and swine respiratory epithelium. Together, these data will increase our understanding of the viral determinants and biological characteristics influencing viral fitness, virus-host interactions, antiviral resistance, and the zoonotic potential of swIAV circulating in European pig populations. Expected results and impact: The proposed project will increase our understanding of the zoonotic potential of swIAV circulating in European pig populations and provide crucial phenotypic data in biologically relevant human and swine respiratory epithelium models. This biological data will complement the surveillance data collected by different members of the ESFLU COST Action and can be incorporated into an overall risk assessment of the zoonotic potential of various swIAV. Furthermore, it may provide insight into the progression or pathogenesis of swine influenza in pigs. Altogether, the proposed project will complement and enhance the existing ESFLU COST Action, strengthening the overall preparedness in Europe, including Switzerland, to rapidly identify and characterize circulating swIAV variants with zoonotic and pandemic potential. Combining the knowledge generated during the proposed project with the ESFLU COST Action will advance the scientific understanding of how certain swIAV variants can successfully establish themselves among different species, contribute to the European network on swIAV, and increase global pandemic preparedness.