Early Events in the JC Polyomavirus Lifecyle (360G-Wellcome-105221_Z_14_Z)

JC Polyomavirus (JCPyV) causes a rapid demyelinating disease, Progressive Multifocal Leukoencephalopathy (PML), in the immune compromised host. Owing to the increase in AIDS in the developing world and the introduction of immune modulating therapies, JC is an emerging pathogen and there are currently no antiviral therapies that specifically target it. Although there has been much research on JC biology, various aspects of the virus lifecycle are not well understood. In this project, we will gain greater insight into the viral lifecycle by utilizing chemical genetics, biochemical assays and cell biological techniques combined with high resolution imaging. Specifically, we will identify the intracellular route of JC infection from initial receptor engagement to nuclear entry, elucidate host proteins that bind to the virus genome to modulate viral infection and dissect the signalling pathways required for productive JC virus infection. Greater understanding of these aspects of the virus lifecycle may provide novel targets for intervention against PML and underpin the discovery of new therapeutics, whilst increasing our knowledge of JC virus biology.