Influenza viruses cause a significant seasonal disease burden and continually threaten to initiate human pandemics. Antivirals are available for treatment of influenza, however drug-resistant viruses often emerge. Thus, there is urgent need to develop new antivirals with lower chances of selecting resistance. As viruses rely extensively on cellular functions, one way to minimise resistance is to target new antivirals against host factors. This concept requires a fundamental understanding of mechanisms underpinning the interplay between influenza viruses and their hosts.
In this project, we will investigate the role that host SUMO pathways play during influenza virus replication. SUMO proteins are important regulators of cell signalling, and are covalently linked to other proteins in order to alter structure, localization or function. As such, SUMO conjugation regulates many diverse aspects of biology. Our own work shows that global cellular SUMOylation increases during influenza virus infection, and that virus replication is severely impaired when cells are depleted of key enzymes and components required for general SUMO conjugation. Here, we will determine what viral components trigger SUMOylation, and which specific cellular enzymes are involved. We will characterize where in the cell SUMO conjugates accumulate, and for the first time apply large-scale affinity-based quantitative proteomics to the identification of proteins that become SUMO modified during infection. A key aim will be to correlate changes to the SUMO sub-proteome with the function of specific host SUMO-modifying enzymes, thereby establishing the mechanistic role of these modifications during virus replication.
Understanding basic mechanisms underlying SUMOylation during influenza virus infection will provide new insights into the fundamental biology of these important pathogens. The work could also lead to identification of key cellular pathways that can be exploited as novel therapeutic targets
- medycyna i nauki o zdrowiumedycyna klinicznafarmakologia i farmacjalekleki przeciwwirusowe
- nauki przyrodniczenauki biologicznebiologia komórkisygnalizacja komórkowa
- nauki przyrodniczenauki biologicznemikrobiologiawirusologia
- nauki przyrodniczenauki biologicznebiochemiabiocząsteczkibiałkaenzymy
- medycyna i nauki o zdrowiunauki o zdrowiuchoroby zakaźnawirus RNAgrypa
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