Glycan hopscotch: decoding how adenoviruses hop, skip, and jump their way into the cell

Many viruses, including several adenoviruses (AdV) are recruited at the cell surface through interactions with heparan sulfate (HS) in the glycan layer covering our cells (glycocalyx).

To lead to successful infection, virus-HS interactions must be tightly modulated to ensure successful navigation through the HS-rich glycocalyx towards the site of entry, without premature trapping.

Interestingly, depending on the AdV type, interaction with HS may facilitate infection or prevent it.We hypothesize that the outcome of the virus-HS interaction correlates with virus dynamics at the cell surface, i.e. the virus’ ability to attach, detach, and diffuse towards its entry point.

To challenge this hypothesis, we quantify the interaction dynamics of various HS-binding AdVs, and study associated modulatory mechanisms.

To do so, we use advanced bioanalytical platforms based on cell-surface mimics, together with live cell microscopy and infection assays.

We probe virion-glycan interactions using single particle tracking as well as particle binding kinetic analysis under equilibrium conditions.

We further use single molecule force spectroscopy to study individual AdV-HS interactions and correlate multi- and monovalent binding.Knowledge of the mechanisms through which HS can promote or block infection is key to understanding how and why AdVs infect certain cells. Such knowledge is also central to the development of AdVs-based vectors as well as antivirals against those pathogens.