Picornavirus Structure Group

Viruses are obligate intracellular parasites. Infection is initiated by virus binding to a specific receptor expressed on the surface of the host cell. For foot-and-mouth-disease virus (FMDV) a number of molecules that belong to the integrin family mediate attachment. Figure 1 shows FMDV co-localised with one such integrin, avb6, at the cell surface. Virus binding is mediated by a highly conserved RGD (argine-glycine-aspartic acid) motif located at the apex of a flexible loop on virus protein 1 (VP1) at the virus surface. We have shown for avb6 that virus binding stimulates virus internalisation into early- and recycling-endosomes (Figure 2) where the prevailing low pH stimulates virus uncoating and transfer of the viral genomic RNA into the cellular cytoplasm. Once inside the cell viral RNA replication takes place on virus-induced membrane vesicles. The interests of my lab are to understand the specificity of FMDV for the different RGD-binding integrins, and the mechanisms of cell entry, penetration of the endosomal membrane by the viral RNA, and induction of virus-induced vesicle formation.