Mucus Physically Restricts Influenza A Viral Particle Access to the Epithelium.

Prior work suggests influenza A virus (IAV) crosses the airway mucus barrier in a sialic acid-dependent manner through the actions of the viral envelope proteins, hemagglutinin, and neuraminidase. However, host and viral factors that influence how efficiently mucus traps IAV remain poorly defined. In this work, how the physicochemical properties of mucus influence its ability to effectively capture IAV is assessed using fluorescence video microscopy and multiple particle tracking. Our studies suggest an airway mucus gel layer must be produced with virus-sized pores to physically constrain IAV. While sialic acid binding by IAV may improve mucus trapping efficiency, sialic acid binding preference is found to have little impact on IAV mobility and the fraction of viral particles expected to penetrate the mucus barrier. Further, synthetic polymeric hydrogels engineered with mucus-like architecture are similarly protective against IAV infection despite their lack of sialic acid decoy receptors. Together, this work provides new insights on mucus barrier function toward IAV with important implications on innate host defense and transmission of respiratory viruses.