Award details

Modification of protein synthesis initiation by foot-and-mouth disease virus proteases

Reference	BBS/E/I/00000896
Principal Investigator / Supervisor	Professor Graham Belsham
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	5,480
Status	Completed
Type	Institute Project
Start date	01/10/2001
End date	30/09/2004
Duration	36 months

Abstract

Picornaviruses, including foot-and-mouth disease virus (FMDV) and poliovirus, have a positive sense RNA genome. The viral RNA functions as a mRNA. However, the 5' non-coding region (5'NCR) of the viral RNA contains extensive secondary structure and, in contrast to other eukaryotic mRNAs, lacks a 5' terminal cap- structure (m7GpppN...). The viral RNA contains a complex RNA element within the 5'NCR which directs cap-independent internal initiation of protein synthesis, termed an IRES (internal ribosome entry site). The cap-structure of cellular mRNAs is recognised by the cap-binding complex eIF4F, comprising eIF4E, eIF4A and eIF4G. The FMDV Leader protease and the unrelated poliovirus 2A protease each induce cleavage of the translation initiation factor eIF4G and results in the inhibition of cap- dependent protein synthesis but they enhance IRES activity. The FMDV 3C protease also modifies translation initiation factors eIF4G and eIF4A. We will analyze other modifications of cellular proteins that are induced by these viral proteases. We will use a novel IRES-dependent cell selection strategy to select transfected cells expressing the individual proteases to examine the status of specific proteins. The effect of the protease- induced modification of specific translation initiation factors on their ability to interact with other initiation factors will be explored.

Summary

unavailable

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
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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