VICI grant for Frank van Kuppeveld

Kuppeveld, Frank van

Dr. Frank van Kuppeveld (Department of Medical Microbiology) has been awarded a 1.5 M Euro VICI grant for his proposal entitled "Viral hijacking of host cell factors and membranes for replication organelle formation".

Viruses are obligatory intracellular parasites that hijack the infrastructure and metabolism of their host cell for efficient propagation. All viruses with a positive-strand RNA genome (e.g. enteroviruses, hepatitis C virus, dengue virus, and SARS-coronavirus) reorganize host cell membranes to form membrane-bound replication complexes in which viral RNA replication takes place. At present, it is largely unknown how viruses hijack host machinery to form these so-called "replication organelles". Recently, we were the first to identify host factors (i.e. GBF1 and PI4K3b) involved in the formation and/or function of replication organelles induced by enteroviruses, an important group of human pathogens that includes poliovirus, coxsackievirus, and rhinovirus. In my VICI proposal, I will investigate the role of novel host factor candidates - identified by my group through a genome-wide RNAi screen - in the formation, architecture, and function of replication organelles, using state-of-the-art virological, molecular, biochemical, and microscopy techniques.

There is growing interest in the potential of inhibiting virus replication by targeting host factors that are critical for the viral life cycle. Cells offer a wealth of potential drug targets which, unlike viral targets, are unlikely to develop resistance in response to therapy. This "host-oriented" approach may allow the development of broad-spectrum inhibitors since many viruses belonging to the same genus or family exploit the same cellular pathway. Therefore, in this project also functional assays for newly identified host factors will be developed and used to identify small-molecule inhibitors of replication of enteroviruses, for which currently no antiviral therapy is available.



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