Project description
A closer look at flavivirus adaptation and evolution
Neurotropic flaviviruses, such as Zika and tick-borne encephalitis, pose severe risks and are transmitted by mosquitoes and ticks, respectively. These viruses, which use immune cells to spread and cause encephalitis, produce double-stranded RNA (dsRNA) that triggers the host’s immune response. However, how these viruses adapt to different host cells and immune systems, particularly in arthropods, remains unclear. With the support of Marie Skłodowska-Curie Actions programme, the FlaviRNA-HMT project will examine how flaviviruses interact with dsRNA in humans versus arthropods. Researchers will use high-throughput proteomics to identify and compare host factors involved in dsRNA-protein complexes across both types of hosts. The study will also explore how these interactions impact viral adaptation and evolution.
Objective
Neurotropic flaviviruses Zika virus (ZIKV) and tick-borne encephalitis (TBEV) represent major emerging arthropod-borne viruses transmitted by two different vectors, either mosquitoes or ticks. In humans, they use cells of the immune system to spread throughout the organism and can lead to severe encephalitis. During their replication, viruses produce double-stranded RNA (dsRNA) structures which is not only a necessary by-product but also performs key regulatory functions and acts as a pathogen-associated molecular pattern recognized by the host innate immune response. However, viral adaptation to such divergent host cells and organisms and their immune response, especially in arthropods, is poorly understood.
In this project, I propose to investigate and compare how neurotropic flaviviruses interact through their RNA in humans and arthropods. First, I will identify host factors involved in protein-dsRNA complexes using anti-dsRNA antibodies in a high-throughput proteomic approach from infected live arthropods and human models for immune and neuronal cells and compare the protein networks between each host. Second, I will select the most significant and relevant hits for a functional screening, further define the function of the best candidates that are either pro-viral or anti-viral, confirm their importance in most relevant models and characterize the molecular functions of the best candidates. Finally, I will identify the dsRNA structures and RNA species interacting with the best candidates, and determine the evolutionary pressure imposed on the viral genomes in each host. Altogether, this project will contribute to unravel the adaptation of neurotropic flaviviruses to their hosts throughout their cycles, both from a mechanistic and evolutionary perspective, help understand the role of the RNA in crossing species barriers and lay the grounds for new therapeutics and disease control strategies against viruses that represent an ever-increasing threat in Europe.
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.
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences zoology invertebrate zoology
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Keywords
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
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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-2022-PF-01
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75794 Paris
France
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