IAH-funded studentship: Entry of Foot-and-Mouth disease virus: investigating the mechanisms of membrane penetration using liposomes as model membranes

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Foot-and-mouth disease virus (FMDV) is one of the most important viral pathogens of agricultural significance. FMDV belongs to the picornavirus family, which also includes important human pathogens, such as poliovirus and rhinovirus (common cold). Infection by FMDV is initiated by virus binding to integrin receptors at the cell surface. Receptor binding triggers cellular internalisation of the virus-receptor complex via clathrin dependent endocytosis. Within endosomes, the prevailing low pH triggers release of the viral genome from the capsid and the transfer of the RNA genome through the barrier of the endosome membrane into the cellular cytoplasm for viral replication to begin. This process of ‘membrane penetration’ is poorly understood for non-enveloped viruses such as FMDV. It is thought that the virus interacts with the endosome membrane in some way, perhaps forming a pore in the membrane, thus allowing the genome to pass through the membrane into the cytoplasm. There is currently no information on how this delivery of the RNA through the membrane is achieved by FMDV. Advances in our understanding of this fundamental stage of the virus life-cycle would be of great significance not only for FMDV but also for other picornaviruses and indeed for all non-enveloped mammalian viruses. This project will use artificial lipid membranes known as liposomes to investigate the molecular mechanisms of membrane interaction and penetration by FMDV. This is an exciting area of research that combines conventional virology techniques such as cell Page 2 of 4 culture and electron microscopy with modern biophysical approaches such as model membranes, fluorescent reporter molecules and mass spectrometry.

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