The interplay of cellular determinants shapes human and avian influenza A virus tropism in the airway epithelium

In contrast, human IAVs also preferentially bind to ciliated cells but independently of α2,6-linked sialic acid abundance. Human IAVs replicate more efficiently than avian IAVs due to their ability to utilize human ANP32 proteins, but they also exhibit cell type–specific differences, with higher viral RNA levels in secretory cells. Thus, preferential binding to ciliated cells coupled with enhanced replication in secretory cells equalizes overall infection levels across cell types for human IAVs.

Together, our findings highlight the spatiotemporal complexity and interplay of IAV infection dynamics in the airway epithelium and redefine current models of influenza A virus tropism.