Project description
Characterisation of the protein complex that triggers an antiviral immune response
The mitochondrial antiviral signalling (MAVS) adaptor protein plays a central role in cell antiviral signalling in response to RNA virus infections, initiated by the cytosolic receptors that trigger the type-I interferon pathway via the MAVS. Recent studies showed that the RNA helicase DDX3 is a new member of the viral cytosolic receptor pool, required to activate the MAVS during the antiviral response. The EU-funded MDR project will focus on the structural and functional characterisation of the MAVS-DDX3-viral RNA (MDR) complex, using biophysical and cellular biology methods. MDR has the central role in triggering an antiviral immune response, making it a potential pharmacological target.
Objective
The mitochondrial antiviral signalling (MAVS) adaptor protein is a central signalling hub for host cells to mount an antiviral response following RNA virus infections, which is initiated by the cytosolic receptors that trigger the type-I interferon (INFs) path through the MAVS. Recently, it has been shown that the RNA helicase DDX3 is a novel atypical member of the viral cytosolic receptor pool and it is required to activate the MAVS during the antiviral response. In fact, DDX3 is crucial in the translation initiation of the HIV-1 RNA and it is identified as viral RNA sensor able to induce the antiviral immunity in dendritic cells (DCs). DDX3 binds to viral RNAs lacking the poly(A) tails, also known as abortive transcripts, and then associates with the MAVS to trigger the production of type I IFN.
Currently, it is unknown how the complex partners MAVS-DDX3-vRNA (MDR) interact for assembly and what is the MDR mechanism of action at molecular level.
The proposed research will be focused on the structural and functional characterization of the MDR complex by biophysical and cellular biology techniques. Notably, silencing DDX3 or MAVS expression suppress DC activation in response to HIV-1 infection, an event that in physiological condition is at the front line of host defence against the HIV-1. Therefore, the central role in triggering antiviral immune response makes MDR a strategic pharmacological target. However, addressing this task requires the MDR structure elucidation in order to exploit its molecular features to create a new generation of adjuvants in anti-retroviral therapy.
This research provides an understanding of how cellular protein sensors interact with retroviral RNA to trigger the native immune response and induce expression of antiviral proteins.
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 RNA viruses
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance multidrug resistance
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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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.
1105AZ Amsterdam
Netherlands
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.