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Controlling Influenza A Virus Liquid Organelles

Project description

A new approach for controlling virus infection

Viral outbreaks necessitate a front line of antiviral strategies since the on-demand development of vaccines or antibody treatment is not always feasible. The EU-funded LOFlu project will investigate the host-pathogen interactions in influenza A virus (IAV) infection. Particular emphasis will be given to viral inclusions with liquid properties that form during viral assembly and constitute a key step in the virus life cycle. By studying how the host and the virus work in concert to coordinate the formation and material properties of IAV liquid inclusions and their interactions, researchers will shed light on the organisation of viral reactions in space and in time, as well as on the principles governing the assembly of IAV epidemic and pandemic genomes.

Objective

The world health organization monitors viral infections worldwide with the aim to coordinate strategies to control viral outbreaks. The on-demand development of vaccines or antibody treatment does not confer a first line of defense against unpredictable infections caused by new viruses in humans such as pandemic influenza, corona or Ebola viruses, and new approaches are needed. We propose to investigate the fundamental basis of novel host-pathogen interactions in influenza A virus (IAV) infection that may define new antiviral strategies. We discovered that the important pathogen IAV induces the intracellular assembly of viral inclusions that behave like liquid organelles. IAV inclusions serve as assembly sites for the IAV segmented genome, a key step in the viral lifecycle. We now find that the maintenance of the liquid character of IAV inclusions is essential for viral replication. As we identified some of the host and viral components of IAV inclusions, we now have the tools to interrogate how specific interactions and cellular processes result in phase-separated compartments. We aim to learn how the function of IAV inclusions is related to their material state and investigate the potential of imposing phase transitions in an organism to limit IAV infection. Phase separation provides a novel conceptual framework to tackle how viruses exploit cells to organize viral reactions in space and in time. It also provides alternative principles for exploring aspects of the IAV lifecycle not yet fully understood, including how influenza epidemic and pandemic genomes assemble. Taken together, we propose a new, integrated approach for studying phase separated phenomena, from the molecular to the organismal level, that will bring a deeper understanding and control to viral infections. Our work will also be of relevance to other fields of biomedicine, including in the science of soft matter that is involved in neurodegenerative diseases and some cancers.

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Keywords

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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.

ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2020-COG

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Host institution

UNIVERSIDADE CATOLICA PORTUGUESA
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.

€ 1 189 117,71
Address
PALMA DE CIMA
1649 023 LISBOA
Portugal

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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.

€ 1 189 117,71

Beneficiaries (2)

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