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.
Publications
- Paul Monaghan, Sarah Gold, Jennifer Simpson, Zhidong Zhang, Paul H. Weinreb, Shelia M. Violette, Soren Alexandersen and Terry Jackson.
(2005)
The avb6 integrin receptor for foot-and-mouth disease virus is expressed constitutively on the epithelial cells targeted in cattle.
Journal of General Virology: 86: 2769-2780.
[Abstract].
- Stephen Berryman, Stuart Clark, Paul Monaghan and Terry Jackson.
(2005)
Early Events in Integrin avb6-Mediated Cell Entry of Foot-and-Mouth Disease Virus.
Journal of Virology: 79: 8519-8534.
[Abstract].
- Paul Monaghan, Hannah Cook, Terry Jackson, Martin Ryan, and Tom Wileman.
(2004)
The ultrastructure of the developing replication site in foot-and-mouth disease virus-infected BHK-38 cells.
Journal of General Virology: 85: 933-946.
[Abstract].
- Terry Jackson, Stuart Clark, Stephen Berryman, Alison Burman, Stephanie Cambier, Dezhi Mu, Stephen Nishimura, and Andrew M. Q. King.
(2004)
Integrin avb8 Functions as a Receptor for Foot-and-Mouth Disease Virus: Role of the b-Chain Cytodomain in Integrin-Mediated Infection.
Journal of Virology: 78: 4533-4540
[Abstract].
- Miller. L. C., W. Blakemore, D. Sheppard A. Atakilit, A. M. Q. King and T. Jackson.
(2001)
Role of the cytoplasmic domain of the b-subunit of integrin avb6 in receptor mediated endocytosis of foot-and-mouth disease virus.
Journal of Virology: 75:4158-4164.
[Abstract].
- Jackson. T., D. Sheppard, M. Denyer, W. Blakemore and A. M. Q. King.
(2000)
The epithelial integrin avß6 is a receptor for foot-and-mouth disease virus.
Journal of Virology: 74:4949-4956.
[Abstract].