Influenza A virus spreads through the respiratory tract in a compartment-specific manner, yet the mechanisms governing its progression remain unclear. Here, we investigated how viral replication and inter-compartment transport shape infection dynamics across the nose, trachea, and lungs. To address this, we developed a multicompartment mathematical model based on a target-cell framework and fitted it to reported viral-load data from mice infected with the Udorn H3N2 strain, using bootstrap estimation to quantify uncertainty. The best-performing model revealed rapid amplification and substantial target-cell depletion in the nose, limited replication, and delayed viral dynamics in the lungs, mainly driven by input from upstream compartments. Transport parameters exceeded local replication rates in deeper regions, indicating that the nose serves as the primary site of viral replication and seeding. Overall, this study highlights the dominant role of the nasal compartment in driving within-host influenza progression.
Blanco-Rodriguez et al. (Wed,) studied this question.