Hijacking cellular membranes for enteroviral genomic RNA replication

EUVIRNA project ESR-1

Project description
Enteroviruses are highly prevalent and important human pathogens. This group includes among others, poliovirus (cause of paralytic poliomyelitis), coxsackievirus (major cause of aseptic meningitis and viral myocarditis), human rhinovirus (cause of respiratory tract infections and asthma exacerbations), and enterovirus 71 (cause of large outbreaks in Asia associated with severe neurological sequelae). Thus far, no potent antiviral drugs are available for treatment of enterovirus infections. The development of antiviral drugs against enteroviruses requires a detailed understanding of the molecular mechanisms of virus replication and the identification of cellular proteins and pathways that are hijacked by the these viruses for efficient replication.

Enteroviruses RNA replication takes place at modified secretory pathway-derived cellular membranes that are hijacked by viral proteins. We have identified GBF1 (a GEF of Arf1, the master regulator of ER-to-Golgi transport, Wessels et al. 2006 Dev Cell) and PI4K (a lipid modifying kinase that is regulated by Arf1, Hsu et al 2010 Cell) as essential host factors for enterovirus replication, but their exact role in viral RNA replication is as yet poorly understood. In this project, the functional role, localization and dynamics of these proteins in infected cells will be investigated in detail by virological, molecular, biochemical and microscopy approaches.

Host institute
Utrecht University, Utrecht, The Netherlands
Department of Infectious Diseases & Immunology, division of Virology
Supervisor: Prof. dr. Frank van Kuppeveld

The department of Infectious Diseases & Immunology, division of Virology, studies the molecular and cellular aspects of replication of (+)RNA viruses (such as enterovirus and Dengue virus) and aims to find and characterize new inhibitors of virus replication.

Position filled