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RNA-protein interactions in the foot-and-mouth disease virion

Reference	BBS/E/I/00000188
Principal Investigator / Supervisor	Dr Andrew King
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	41,164
Status	Completed
Type	Institute Project
Start date	01/04/1997
End date	30/09/1998
Duration	18 months

Abstract

Once in the cytoplasm of the host cell, the genome of a positive strand RNA virus like foot-and-mouth disease virus (FMDV) is endowed with all the information needed to initiate a productive infection. Although much is known about how FMDV attaches to cellular receptors, how it subsequently transfers its genome across the cell membrane remains an outstanding mystery for FMDV, as it is to varying degrees for all viruses, especially non-enveloped viruses. A method for making empty FMDV capsids in large amounts from vaccinia virus vectors has been developed at the IAH, and it is intended to combine this technology with standard, cDNA- based, methodology for genetically manipulating the FMDV genome, and thereby develop an efficient system for producing complete virus particles (capsid plus RNA genome) carrying lethal defects. In the first instance, this will be used to make 'provirions', in which the protein cleavage that normally accompanies encapsidation is blocked, in order to investigate the role of this priming step in cell infection. Technology developed in this project will provide the means for investigating a crucial - arguably the crucial - aspect of the way FMDV invades and moves between cells. A particular advantage will be the ability to propagate the products of reverse genetics in amounts sufficient for studying, not merely function (which can be done already; see 046), but also atomic structure, so making this project especially relevant to the aims of the ASD. The project would also provide a versatile experimental tool with which to address other aspects of FMDV molecular biology with which the Institute programme is concerned, including genome encapsidation and, with some further development, replication. Finally it represents a form of generic biotechnology with applications in the field of gene therapy. This PhD studentship project, currently in its first year, has strategic goals whose outputs will take the form, described in the preceding subsection, of enabling technology and fundamental understanding of protein/RNA interactions during virus assembly and internalisation. In due course, it should also yield data meriting one or more publications. Commercially exploitable IP is unlikely, although the potential will be kept under review.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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