RT Journal Article SR Electronic T1 Mucus physically restricts influenza A viral particle access to the epithelium JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.08.14.553271 DO 10.1101/2023.08.14.553271 A1 Kaler, Logan A1 Engle, Elizabeth M. A1 Iverson, Ethan A1 Boboltz, Allison A1 Ignacio, Maxinne A. A1 Rife, Maria A1 Scull, Margaret A. A1 Duncan, Gregg A. YR 2023 UL http://biorxiv.org/content/early/2023/08/14/2023.08.14.553271.abstract AB 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, we assessed how the physicochemical properties of mucus influence its ability to effectively capture IAV with altered sialic acid preference using fluorescence video microscopy and multiple particle tracking. We found an airway mucus gel layer must be produced with pores on the order of size of the virus to physically constrain IAV. Sialic acid binding by IAV also improves mucus trapping efficiency, but interestingly, sialic acid preferences had little impact on the fraction of IAV particles expected to penetrate the mucus barrier. Together, this work provides new insights on mucus barrier function toward IAV with important implications on innate host defense and interspecies transmission.Competing Interest StatementThe authors have declared no competing interest.