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Experimental Virology for Assessing Disease Emergence Risks

Project description

Studying zoonotic viral threats

Wild animal viruses are a real threat to public health, as demonstrated by Ebola outbreaks and the COVID-19 pandemic. However, little is known about how these viruses function. The EU-funded EVADER project will investigate viral emergence from an evolutionary standpoint. By studying how host range mutants appear and adapt to human cells, it will deliver the most comprehensive landscape of viral human cell infectivity to date. The project will also study the receptor-dependent cell tropism of enveloped RNA viruses – an experimentally tractable process involved in viral emergence. Finally, it will provide important clues about the role of spontaneous mutation in viral emergence and explore the feasibility of clade-level antiviral therapies.

Objective

The emergence of new human pathogenic viruses from animal reservoirs is an increasing concern, but also a poorly understood process. Massive sequencing programs have been recently launched to characterize wildlife viruses, but empirical information on how these viruses function and whether they can potentially infect humans is needed. However, the isolation and culturing of wildlife viruses is too often unfeasible due to technical issues, biosafety concerns, or lack of full-length sequence information. Furthermore, we need to investigate viral emergence from an evolutionary standpoint to better understand how host-range mutants appear and adapt to human cells. To achieve these goals, we will focus on the receptor-dependent cell tropism of enveloped RNA viruses, a central and experimentally tractable process involved in viral emergence. First, we will use high-throughput gene synthesis to create hundreds of pseudoviruses coated with the envelopes of previously uncharacterized wildlife viruses belonging to different families, and we will examine their ability to infect a panel of humans cells from various tissues. This will deliver the most comprehensive landscape of viral human cell infectivity to date. Second, we will use experimental evolution, massive parallel sequencing, and site-directed mutagenesis to explore how viral envelopes diversify, undergo cell tropism shifts, and adapt to human cells. This will provide important clues about the role of spontaneous mutation in viral emergence, and may reveal repeatable evolutionary pathways that could help us improve outbreak predictability. Finally, we will use our experimental results to infer candidate cell receptors for wildlife viruses using machine learning, and to explore the feasibility of broad-range, clade-level antiviral therapies that could be used for combating emerging viruses in the future.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2020-ADG

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Host institution

UNIVERSITAT DE VALENCIA
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.

€ 2 436 500,00
Address
AVENIDA BLASCO IBANEZ 13
46010 Valencia
Spain

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Region
Este Comunitat Valenciana Valencia/València
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.

€ 2 436 500,00

Beneficiaries (1)

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