Molecular mechanisms behind filovirus entry and egress: the role of viral glycoprotein glycosylation

Filoviruses are amongst the most dangerous human pathogens. They pose a great health concern, due to a growing number of emerging species, that vary in tropism and pathogenicity.

In my work, I aim at establishing a correlation between filoviruses pathogenicity, the characteristics of their interaction with the cell membrane and their entry and egress potential. In this context, I hypothesize that viral carbohydrates are key in modulating these processes. For this study, I have selected a number of filovirus species, distinct in their pathogenicity for humans.

I will use a transcription and replication competent virus like particle system (trVLP) as a BSL-2 virus model, and will produce particles presenting the glycoproteins (GP) from the different filovirus species of interest. GP is the sole glycoprotein found on the virus surface and is crucial for filovirus attachment and entry.

Using an interdisciplinary approach combining virology, biophysics and glycobiology, I will first carry out infection assays, to characterize the entry and egress potential of the different particles.

I will further investigate the role of two key attachment molecules, heparan sulfate and DC-SIGN in modulating those processes.

This will be achieved first on the cellular level, and then on the molecular level, using single molecule force spectroscopy to look at the characteristics of individual ligand-receptor bonds.

Extensive glycomic analysis, amongst other via mass spectrometry, will further address the hypothesis that the GPs glycan profile plays a key role in determining the behaviour of the different filoviruses.

Taken together, I will provide a comprehensive description of the influence of the different GPs in viral entry and egress, on the molecular, functional, and biological levels. Such insights will without doubt be key to the development of efficient and broad-spectrum antivirals.