Project description
Unravelling enterovirus-host interactions for antiviral targets
Enteroviruses, a genus that includes pathogens such as poliovirus and rhinovirus, cause diseases ranging from mild colds to severe, life-threatening conditions. Vaccinating against all enteroviruses is impractical due to their vast number, highlighting the urgent need for pan-enterovirus antiviral drugs. While mammalian cells deploy antiviral mechanisms such as stress granules (SGs) to curb viral replication, enteroviruses counteract these defences using the 2A protease (2Apro). However, critical gaps remain in understanding how these cellular defences operate and are subverted by viruses. Supported by the Marie Skłodowska-Curie Actions programme, the BARONET project seeks to unravel the dynamics of antiviral condensates in enterovirus-infected cells. Using advanced microscopy, it aims to uncover virus-host interactions and identify potential therapeutic targets for innovative antiviral strategies.
Objective
The genus Enterovirus comprises many important human pathogens (e.g. polio-, coxsackie-, and rhinovirus) that cause a wide array of diseases ranging from mild to life-threatening. As there are hundreds of enteroviruses and vaccination to all of these is not feasible, there is an unmet need for pan-enterovirus antiviral drugs. Hence, we need to deepen our knowledge on the enterovirus life cycle and virus-host interactions.
Mammalian cells express an arsenal of sensors that function to restrict virus replication and spreading. These include RIG-I and MDA5, which recognize viral RNA and trigger expression of type I interferon (IFN), and PKR, a kinase that upon recognition of viral RNA blocks translation and triggers the formation of membrane-less condensates, so-called stress granules (SGs), that serve as platform for RIG-I and MDA5 signaling. On the other hand, viruses have developed sophisticated mechanisms to suppress antiviral responses. The enterovirus 2A protease (2Apro) has been recognized by the host lab to antagonize SG formation and IFN-gene transcription.
Emerging evidence points towards the existence of many more types of condensates with a role in antiviral signaling, such as PKR clusters, RNase L bodies, and cGAS foci. Unfortunately, comprehensive insight into the composition, formation, and dynamics of these condensates in infected cells are missing. In this project, I aim to comprehensively characterize antiviral condensates in cells infected with wild-type enterovirus or a 2Apro inactive mutant. I will use state-of-the-art microscopy approaches, including an assay that was recently developed by the host lab and that allows real-time visualization of the viral life cycle. Besides, I will assess the role of condensates as signaling platforms that connect stress sensors with effectors of the innate immune response in infected cells. This project will provide insights into enterovirus-host interactions and may uncover new targets for antiviral therapy.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences health sciences infectious diseases viral diseases RNA viruses
- natural sciences biological sciences microbiology virology
- natural sciences physical sciences optics microscopy
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- natural sciences biological sciences genetics RNA
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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.
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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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.
3584 CS Utrecht
Netherlands
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