Deciphering the nanobiophysics of virus-host interactions in 3D cellular systems

Introduction

The current pandemic demonstrates how viruses represent a major threat for human health. Viral infection is a complex multistep process involving both the virus and the host cell machinery. The very first stage consists of landing and binding of the virus, followed by host cell entry, and then the release of the viral genetic material into the cell.

Virus Entry Pathways

Entry pathways are largely defined by the preliminary interactions between viruses and their receptors at the cell interface. Elucidating this complex interplay is a crucial step towards establishing a full picture of the infection process and may lead to the discovery of new antiviral drugs targeting viral entry.

Limitations of Current Knowledge

Our current knowledge of virus-host interactions mainly relies on the use of cancerous model cell lines cultured in 2D that far from mimic the 3D in vivo conditions of tissue, such as cell heterogeneity and complex organization. Hence, there is an urgent need to develop an innovative platform to monitor and quantify the molecular forces and dynamics at play during the entry pathways in such complex environments.

Project Ambition

The ambition of this proposal is to unravel virus-host interactions under physiologically relevant 3D conditions by combining single-virus atomic force microscopy and optical tweezer techniques. By means of cellular models of increasing complexity, we will decipher the complex relationship between the organization and heterogeneity of epithelium and the early stages of viral infection.

Scientific and Medical Impact

At the frontiers of nanobiophysics and virology, this project will push the limits of advanced nanotechniques to understand the molecular mechanisms of virus entry in unprecedented 3D in vivo conditions. This project will have strong scientific and medical impacts:

1. In virology, it will strongly enhance our molecular understanding of virus-host interactions.
2. In medicine, our new methodology will contribute to the identification of new compounds that target viral infection and the innate immune response.