Tissue tropisms of avian influenza A viruses affect their spillovers from wild birds to pigs.

Wild aquatic birds maintain a large genetically diverse pool of influenza A viruses (IAVs), which can be transmitted to lower mammals and ultimately humans. Through viral replication efficiency phenotypic analyses, only a small set of avian IAVs replicated well in the epithelial cells of swine upper respiratory tracts, and these viruses were shown to infect and cause virus shedding in pigs. Such a phenotypic trait in viral replication efficiency appears to emerge randomly and are distributed among IAVs across multiple avian species, geographic and temporal orders, and is determined not by receptor binding preference but other markers across genomic segments, such as those in the ribonucleoprotein complex. This study demonstrates that viral replication efficiency phenotypic variants exist among avian IAVs, only a few of which may result in viral shedding in pigs upon infection, providing opportunities for these viruses to become pig adapted, thus posing a higher potential risk for creating novel variants or detrimental reassortants within pig populations.IMPORTANCE Swine serve as a "mixing vessel" for generating human influenza pandemic strains. All HA subtypes of IAVs can infect swine; however, only sporadic cases of avian IAVs are reported in domestic swine. The molecular mechanisms affecting avian IAVs ability to infect swine are still not fully understood. Through phenotypic analyses, this study suggested that tissue tropisms (i.e., in swine upper respiratory tracts) of avian IAVs affect their spillovers from wild birds to pigs, and this phenotype was determined not by receptor binding preference but by other markers across genomic segments, such as those in the ribonucleoprotein complex. In addition, our results showed that such a phenotypic trait was sporadically and randomly distributed among IAVs across multiple avian species, geographic and temporal orders. This study suggested an efficient way for risk assessment of avian IAVs, such as in evaluating their potentials to be transmitted from avian to pigs.