Influenza A viruses use multivalent sialic acid clusters for cell binding and receptor activation
Fig 6
Model for IAV-mediated cell binding, receptor search and activation.
Using quantitative STORM imaging, we could show that SA-conjugated IAV AF as well as one functional receptor, EGFR, form nanodomains in the plasma membrane of A549 cells. While dense AF nanodomains constitute an attractive multivalent binding platform, their diversity in local AF concentration suggests a variety of different residence times for which IAV would stay bound within these domains. Using single-virus tracking, we observed a mixed diffusive—confined motion, that could be simulated using our quantitative SA cluster information. These data suggest a receptor concentration-driven lateral search mechanism between SA enriched nanodomains. Eventually, since AF domains partly overlap with EGFR, IAV encounters a functional receptor that can be activated to signal cell entry. Our data further suggest that a stable preformed EGFR cluster population is activated during IAV stimulation, thereby possibly facilitating efficient signal transduction. EGFR clusters are stabilized by lipid rafts as well as cortical actin.