RT Journal Article
SR Electronic
T1 Influenza A virus diffusion through mucus gel networks
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.14.251132
DO 10.1101/2020.08.14.251132
A1 Logan Kaler
A1 Ethan Iverson
A1 Shahed Bader
A1 Daniel Song
A1 Margaret A. Scull
A1 Gregg A. Duncan
YR 2020
UL http://biorxiv.org/content/early/2020/08/14/2020.08.14.251132.abstract
AB In this study, influenza A virus (IAV) and nanoparticle diffusion in human airway mucus was quantified using fluorescent video microscopy and multiple particle tracking. In previous work, it was determined that mucin-associated sialic acid acts as a decoy receptor for IAV hemagglutinin binding, and that virus passage through the mucus gel layer is facilitated through the sialic-acid cleaving enzyme, neuraminidase (NA), also present on the IAV envelope. However, our data suggests the mobility of IAV in mucus is significantly influenced by the mesh structure of the gel, as measured by nanoparticle probes, and NA activity is not required to facilitate virus passage through mucus gels. Using newly developed analyses, the binding affinity of IAV to the 3D mucus meshwork was estimated for individual virions with dissociation constants in the mM range, indicative of weak and reversible IAV-mucus interactions. We also found IAV diffusion significantly increased in mucus when treated with a mucolytic agent to break mucin-mucin disulfide bonds. In addition, IAV diffusion was significantly limited in a synthetic mucus model as crosslink density was systematically increased and network pore size was reduced. The results of this work provide important insights on how the balance of adhesive and physical barrier properties of mucus influence the dissemination of IAV within the lung microenvironment.Competing Interest StatementThe authors have declared no competing interest.