Award details

Studentship: Understanding the molecular mechanisms of cellular RNA degradation by pathogenic viruses.

Reference	BBS/E/I/00001762
Principal Investigator / Supervisor	Professor John Fazakerley
Co-Investigators / Co-Supervisors	Dr Rennos Fragkoudis
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	24,800
Status	Completed
Type	Institute Project
Start date	01/10/2012
End date	30/09/2016
Duration	47 months

Abstract

Studentship : Pathogenic viruses as parasites depend entirely on cell’s transcription machinery to express and translate their gene products necessary for a successful infection cycle. At the cellular level, this process leads to cell death; at the tissue and organ levels this process leads to loss of organ function and disease. A number of viral proteins have been shown to interfere directly with cell’s transcription machinery causing almost complete loss of cellular RNA pool. This phenomenon of loss of cellular RNA on a global scale is termed host shutoff. Paradoxically, physiological RNA turnover is also a key component of gene regulation and RNA degradation pathways play a key role in this process. Taken together, these observations imply a critical balance between physiological and pathological (virus-mediated) RNA degradation mechanisms which in turn will determine the outcome of viral infections. A recent interest in this field has been the role of RNA-binding cellular proteins which, in general, protect mRNA from cellular degradation machinery. Therefore, the aim of this project is profile these RNA-binding proteins and their associations with cellular and viral transcripts during infection with the murine ?-mmaherpesvirus-68 (MHV-68; a dsDNA virus) and with Semliki Forest Virus (SFV; an RNA virus). The key experimental approaches will include localisation of RNA-binding proteins in cells infected with MHV-68 and SFV by confocal microscopy and by polysome profiling. The latter will help identify transcripts which by-pass degradation machinery and their association with RNA-binding proteins. These approaches will help identify mechanisms by which viral transcripts may overcome degradation and at the detriment of cellular transcripts during host shutoff.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Animal Health, 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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