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Breaking down arenavirus cell entry

Objective

Hemorrhagic fever viruses are serious human threats for which we don’t have adequate treatments available, which is painfully highlighted by the current Ebola virus outbreak in Western Africa. These viruses are obligatory intracellular parasites that make use of the host machinery at every phase of their infection cycle. Virus attachment and entry are the initial steps, which requires engagement of a viral glycoprotein with a cell surface receptor. This interaction then triggers internalization of the virus particle via a Trojan horse-like vesicular pathway, eventually resulting in the release of the viral genome into the cytoplasm of the target cell. We have recently shown that cell entry of at least some hemorrhagic fever viruses (i.e. Ebola virus and Lassa virus) is even more sophisticated, as it requires triggered-recognition of an intracellular receptor as an unexpected additional step. A precise understanding of how these major pathogens enter cells is required to reveal the mechanisms by which they cause disease. In this application, I will combine targeted engineering of viral systems with a genomics approach that enables crystal-clear, yeast-like genetics in human cells. Focusing on arenaviruses, these genome-wide surveys will reveal host factors indicative of virus entry tactics never observed before. I will use biochemistry, microscopy, and cell biological assays to examine in detail the virus-host interplay with these factors and will identify promising new antiviral targets for arenavirus family members that cause human disease. Overall, I foresee that this project will provide a much-needed window on the unique cell entry strategies of these lethal pathogens, which thus far revealed a surprising diversity in the biological host networks being hijacked to establish infection.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-RI - RI – Reintegration panel

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2014

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Coordinator

STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
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.

€ 165 598,80
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.

€ 165 598,80
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