Description du projet
Dévoiler les modulateurs clés de l’immunité antivirale
Le déclenchement d’une réponse immunitaire contre les virus est d’une importance capitale pour la santé humaine. Le projet ProDAP, financé par l’UE, étudie les interactions entre les protéines virales et celles de l’hôte qui régulent les réponses des cellules immunitaires. Grâce à la spectrométrie de masse et à la modélisation statistique, les chercheurs ont identifié les protéines de l’hôte qui, lors d’une infection virale, modifient leur capacité d’interaction ou leur taux de renouvellement. Ces protéines semblent être cruciales pour l’immunité antivirale, et leur caractérisation détaillée aidera à disséquer les voies complexes de la réponse immunitaire. La compréhension de la régulation de l’interaction hôte‑pathogène devrait conduire à de nouvelles stratégies antivirales.
Objectif
The innate antiviral defense system is of central importance to protect from viral pathogens. Its ability to mitigate a detrimental outcome of an infectious event relies on interactions that happen between viral and host-derived proteins as well as on signalling cascades that regulate the cellular response. However, despite the importance of these interactions, the involved processes and proteins are not yet fully understood.
We established state of the art mass spectrometry techniques and statistical modelling to characterise protein-protein interactions that are affected by viruses. We identified a class of proteins we name “viral affected proteins changing their interaction” (iVAPs). In addition, we established protein turnover rates of >6900 proteins in virus infected cells and identified a group of “viral affected proteins changing turnover rates” (tVAPs). tVAPs are regulated on basis of protein stabilisation, degradation or translation. Preliminary experiments show critical importance of iVAPs and tVAPs in antiviral immunity, suggesting functional similarities to Interferon stimulated genes (ISGs). Alike ISGs, VAPs therefore represent a critical component of the immune system.
ProDAP will establish the function of iVAPs and tVAPs in the antiviral immune response. Systematic screens employing depletion and overexpression experiments, integration of these data in functional networks and mechanistic follow up studies will be performed. Already identified and new candidate proteins will be tested mechanistically for their immune-regulatory capacity and their influence on virus infections in vitro and in vivo.
ProDAP will allow insights in yet unstudied modulators of host-pathogen interplay and will influence our current understanding of immune regulation in general. It is well established that ISGs are of central importance to defend virus infections and we hypothesize that VAPs may fulfil a similarly important protective function that has yet not been elucid
Champ scientifique
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health sciencesbasic medicineimmunology
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals
Mots‑clés
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
80333 Muenchen
Allemagne