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Identification of bat antiviral innate immune effectors

Project description

Uncovering bat antiviral defences

Innate immunity is the body's first line of defence against viral infections, providing an immediate, non-specific response to invading pathogens. This protective system includes a variety of antiviral factors and cells that detect and inhibit viral replication, preventing the spread of infection and activating the adaptive immune response. Funded by the Marie Skłodowska-Curie Actions programme, the batAVIRPro project focuses on the immune mechanisms of bats, given that some recent disease outbreaks have been linked to zoonotic viruses originating from bats. Researchers aim to identify key antiviral effectors in bat genomes using bioinformatics and molecular virology techniques. Any promising antiviral candidates will be extensively characterised and brought forward for validation.

Objective

Numerous recent disease outbreaks have been linked to zoonotic viruses originating from bats, including Marburg, Nipah, and the severe acute respiratory viruses like SARS-CoV-2. Countless virus-host encounters during bat evolution have shaped chiropteran immunity to balance defense and tolerance to viral infections, ultimately participating in bats current interplay with viruses and capacity as a viral reservoir.
One of the first barriers against invading pathogens is the innate immunity, which notably includes antiviral factors that directly or indirectly inhibit the replication of invading viruses in the host cell. Recent research on bats showed the functional diversification of several antiviral effectors underscoring their pivotal role in bat immunity. However, because only a handful have been studied, my goal is to identify key and novel antiviral effectors within bat genomes, employing a bioinformatics-driven approach coupled with cellular and molecular virology techniques. First, I will perform genomic, transcriptomic and phylogenomic analyses to identify the genes expressed in immune pathways and under strong positive selection during bat evolution (denoting their in vivo importance). Second, I will characterize the most promising candidates, by genetic knockout and overexpression of variants in bat and human cell lines. Finally, the antiviral activity of the candidates will be tested against a broad spectrum of viruses: retroviruses, positive- and negative-strand RNA viruses.
Taken together, the proposed project will not only identify novel antiviral factors in bats, which are also active in human cells, but will also shed light on the adaptive processes of chiropteran innate immunity, which occurred during bat evolution.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
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.

€ 195 914,88
Total cost

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