Filovirus interactions on the cell surface: finding the sweet spots

The filoviruses Ebola and Marburg are among the most deadly human pathogens, which motivates a comprehensive understanding of their biology and pathogenicity towards the development of mechanism-based therapeutics.Viral attachment to the host surface, diffusion to the point of entry, and detachment of viral progeny upon egress are all potentially druggable steps in the virus life cycle.

Nevertheless, mechanistic studies of these events have so far remained limited due to the lack of advanced techniques to these highly dynamic processes occurring at the cell surface.

This cutting-edge biophysical approaches developed in my lab provide the unique opportunity to systematically study how these dynamic processes are regulated.

Based on our previous work, we hypothesize that these interactions are modulated on a molecular level by i) the nature of the mucin-like domains (MLDs), a highly glycosylated domain found on the viral glycoprotein GPs, and ii) the nature of cellular glycosaminoglycans (GAGs), major constituents of the glycocalyx covering the cell.

To determine the role of these two factors, we will first study how individual virus particles interact with isolated GAGs before studying virus attachment, detachment, and diffusion on the surface of living cells and through the glycocalyx.This project will not only reveal key aspects of the filovirus biology, it will also elucidate common mechanisms used across GAG-binding viruses.