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Illuminating the enteroviral life cycle

Project description

Novel technology to study enterovirus life cycle at the single-cell level

Enteroviruses are highly prevalent pathogens that include poliovirus, coxsackievirus, enterovirus-A71, enterovirus-D68, and rhinovirus. There is an urgent need for technologies that allow sensitive real-time observation of the dynamics and localisation of viral RNA, viral proteins, and host factors at the single-cell level to answer important questions about the enterovirus life cycle. The EU-funded VIRLUMINOUS project aims to develop recombinant reporter viruses for real-time imaging technology to visualise and dissect the spatial and temporal regulation of different phases of the virus life cycle. The technology will be used to study viral RNA replication, virus assembly and release in living cells. The project's insights into the molecular interplay between enteroviruses and their hosts will be crucial for developing antiviral therapies.

Objective

Enteroviruses are highly prevalent pathogens that have enormous clinical and socio-economic impact. Well-known examples are poliovirus, coxsackievirus, enterovirus-A71, enterovirus-D68, and rhinovirus. Although important insights have been obtained in the enteroviral life cycle, many important questions remain unanswered due to shortcomings of current imaging and biochemical methodologies. There is a high need for novel technologies that allow sensitive and real-time observation of the dynamics and localisation of viral RNA, viral proteins, and host factors at the single-cell level.

My long-term goal is to understand enterovirus replication and translate knowledge into the development of antiviral drugs. My lab has a long-standing track record and has made many important contributions to understanding the molecular mechanisms of enterovirus replication and the formation of viral replication organelles. Recently, we constructed a reporter virus that in combination with high-resolution microscopy allowed for the first time to visualize translation, and the regulation thereof, of single (entero)viral RNAs in living cells.

The goal of this project is to visualize and dissect the spatial and temporal regulation of different phases of the enterovirus life cycle. As a first step, novel recombinant reporter viruses for application in real-time imaging technologies will be developed. These viruses will be used to study viral RNA replication, virus assembly, and pre-lytic virus release in living cells. Moreover, they will be instrumental to study the structure and composition of the viral replication organelles and the associated replication complexes through advanced cryo-electron microscopy and tomography technologies, and proteomics/lipidomics analysis, respectively.

This project will lead to important new insights into the molecular interplay between enteroviruses and their hosts, which is essential for developing urgently needed antiviral drugs.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2021-ADG

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Host institution

UNIVERSITEIT UTRECHT
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.

€ 2 396 392,00
Address
HEIDELBERGLAAN 8
3584 CS Utrecht
Netherlands

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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.

€ 2 478 311,25

Beneficiaries (1)

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