The cellular mechanisms of foot-and-mouth disease virus infection

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

The Picornavirus Structure Group (PSG) carries out novel, fundamental research aimed at improving knowledge of the cellular mechanisms of infection by foot-and-mouth disease virus (FMDV). The main research interests of the PSG are the receptors used to initiate infection, and the mechanisms of intracellular virus replication. We have identified four of the five known receptors used by FMDV. This information is allowing us to investigate the molecular determinates of receptor recognition, how FMDV enters its host cell, intracellular virus trafficking, the mechanisms of membrane penetration by the viral genome, and the regulated expression of FMDV receptors on the epithelial cells target by the virus in the animal host. FMDV receptors are also being developed as 'universal' virus-capture ligands in a number of different detection assays for FMDV diagnosis. Once in the cytosol, the viral RNA functions as a template for the synthesis of the viral proteins and the complementary negative-strand genome copies which are, in turn, used as a template for the synthesis of new progeny genomes. FMDV replication takes place on virus-induced vesicles which are believed to function as 'platforms' 'to facilitate assembly of the viral replication complex. Here, we are interested in identifying the viral and cellular proteins that trigger host-cell membrane rearrangements and the cellular origin of the vesicles induced on infection, and to characterise the replication complex. The PSG also contributes to the DEFRA funded Global FMDV Research Alliance (GFRA) that works towards achieving better disease control by the production of novel vaccines and anti-virals.

Publications

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Seago J (2012) Characterization of epitope-tagged foot-and-mouth disease virus. in The Journal of general virology

 
Description Our findings can be used to further investigate pathogenicity of FMDV. Epitope-tagged foot-and-mouth disease virus can be used for virus purification and to study pathogenicity The FMDV receptor, integrin alpha-v / beta6 (avb6), can be developed as a capture ligand in a variety of diagnostic assays for foot-and-mouth disease. Foot-and-mouth disease virus exhibits an altered tropism in the presence of specific immunoglobulins, enabling productive infection and killing of dendritic cells. This will inform vaccine design. Identified a clathrin independent macropinocytosis-like entry mechanism used by bluetongue virus-1 during infection of BHK cells. This information can help investigate cell-entry by field isolates of the virus and the host cell response to infection. Foot-and-mouth disease virus replicates only transiently in well-differentiated porcine nasal epithelial cells. This will allow studies into hoe FMFDV crosses epithelial barriers.
First Year Of Impact 2009
Sector Other