Project description
Unveiling key modulators of antiviral immunity
Eliciting an immune response against viruses is of central importance for human health. The EU-funded ProDAP project is investigating the interactions between viral and host-derived proteins that regulate immune cell responses. Using mass spectrometry and statistical modelling, researchers have identified host proteins that upon viral infection alter either their interaction capacity or turnover rate. These proteins seem to be crucial for antiviral immunity, and their detailed characterisation will help dissect the complex immune response pathways. Insight into the regulation of the host–pathogen interplay is expected to lead to novel antiviral strategies.
Objective
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
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Funding Scheme
ERC-COG - Consolidator GrantHost institution
80333 Muenchen
Germany