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

Project description

Understanding virus-host interactions in 3D physiological environments

Viral infections typically involve the binding of viruses to host cells, their entry into the cells, and the release of genetic material, processes that are crucial for antiviral drug development. However, current research predominantly relies on 2D cancer cell cultures, which fail to replicate the complexity of living tissues. The ERC-funded SingViroPhys project will explore virus-host interactions in 3D physiological environments using cutting-edge techniques like single-virus atomic force microscopy and optical tweezers. By employing increasingly sophisticated cellular models, the project will delve into how the organisation of epithelial cells influences the early stages of viral infection. This research will advance virology and nanobiophysics, providing insights into the molecular mechanisms of virus entry, with implications for antiviral strategies.

Objective

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

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(opens in new window) ERC-2022-COG

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Host institution

UNIVERSITE CATHOLIQUE DE LOUVAIN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 867 346,00
Address
PLACE DE L UNIVERSITE 1
1348 LOUVAIN LA NEUVE
Belgium

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Region
Région wallonne Prov. Brabant Wallon Arr. Nivelles
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 867 346,00

Beneficiaries (1)

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