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BBSRC-funded studentship: Role of FMDV non-structural proteins 2BC in the pathogenesis of infection

Reference	BBS/E/I/00001346
Principal Investigator / Supervisor	Dr Geraldine Taylor
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	11,400
Status	Completed
Type	Institute Project
Start date	01/10/2007
End date	30/09/2011
Duration	48 months

Abstract

Infection of cells with picornaviruses leads to the generation of intracellular membrane vesicles and disruption of the host cell secretory pathway. These events are caused by non-structural proteins encoded by the P2 and P3 regions of the picornavirus genome. To date, most of these studies have used poliovirus. Poliovirus 3A disrupts protein trafficking between the ER and Golgi apparatus, resulting in a reduction in interferon (IFN)-beta and pro-inflammatory cytokine secretion, and a reduction in cell surface expression of proteins involved in immune recognition. These effects could be significant in viral pathogenesis and limit both the inflammatory and immune responses associated with infection. Foot-and-mouth disease virus (FMDV) causes an economically important disease of cloven-hoofed livestock. The main barrier to the effective control of FMDV through vaccination is the establishment of persistent infections in infected and vaccinated ruminants. This suggests that the virus can inhibit components of the innate and/or adaptive immune defences. In contrast to poliovirus, the FMDV 2BC, and not the 3A protein, blocks the secretory pathway. Recent studies have demonstrated that the block in ER-to-Golgi transport is dependent on 2B and 2C, whereas the site of the block is determined by the subcellular location of 2C. Our hypothesis is that inhibition of the ER-to-Golgi transport of proteins by FMDV 2BC inhibits the secretion of IFNs and pro-inflammatory cytokines and modulates recognition of infected cells by the immune system. Such effects could contribute to the development of persistent FMDV infection. This project will determine the role of 2BC in the pathogenesis of FMDV infection by investigating the effects of 2BC on cytokine secretion; identifying the region(s) of 2BC involved in inhibition of protein trafficking; and by determining if 2BC plays a role in immune evasion and contributes to virus persistence, in vivo.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Animal Health, Immunology, Microbiology
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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