Integrated Simulation for Identifying the Key Driver of Strain-Specific Airborne Infectivity of Influenza Viruses.

Airborne transmission plays a central role in the spread of seasonal influenza; however, the determinants governing strain-specific airborne infectivity remain poorly understood. Here, we integrated exposure-infection assays with controlled bioaerosol chamber experiments to quantitatively resolve differences between influenza A and B viruses across aerosolization and aging processes. By coupling these measurements with an effective inhaled dose model, we enabled strain-resolved comparisons of exposure potential as a function of host age and activity level. Our results show that strain-dependent differences in aerosolization efficiency, hygroscopic behavior, virion morphology, and physical stability cannot fully account for variations in airborne infectivity. Instead, biological inactivation during aerosol aging emerges as a key factor governing the loss of infectivity in airborne particles. Accordingly, A/H3N2 maintains higher aerosol-phase infectivity across size ranges, whereas influenza B strains display more rapid loss of infectivity. Collectively, these findings identify aerosol-phase biological stability as a primary determinant of strain-specific airborne infectivity and provide a quantitative framework for assessing the aerosol exposure potential of emerging influenza variants and informing indoor respiratory health interventions.