Award details

Studentship: Characterisation of molecular targets for differential regulation of the type I interferon induction pathway by rotavirus NSP1

Reference	BBS/E/I/00001993
Principal Investigator / Supervisor	Dr Tobias Tuthill
Co-Investigators / Co-Supervisors	Dr Mark Boyce
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	56,477
Status	Completed
Type	Institute Project
Start date	06/01/2014
End date	31/03/2017
Duration	38 months

Abstract

In recent years it has become increasingly apparent how important the induction of type I interferons (IFN a/ß) in response to the detection of pathogen associated molecular patterns (PAMPs) is in reducing the replication of almost all viruses, before adaptive immune responses are mounted. Most viruses are now known to express an interferon antagonist that reduces type I interferon induction or signalling, resulting in the suppression of an antiviral state which would otherwise reduce virus replication and virulence. Rotaviruses comprise one genus in the Reoviridae family of segmented double stranded RNA viruses. Worldwide, rotaviruses are the major cause of acute viral gastroenteritis in the young of a wide range of mammals including economically important livestock animals and humans. The resulting acute dehydrating diarrhoea and its associated morbidity is a major cause of economic loss to the agricultural industry in livestock animals including cattle and swine. NSP1 is the most variable protein encoded by the group A rotaviruses, unusually for a non-structural protein, and was recently characterised as an interferon antagonist. NSP1 was originally found to be associated with a virulent phenotype in mice in a study of genome segment reassortment between a virulent and non-virulent strain. Recent functional studies have shown that NSP1 reduces the transactivation of the type I interferon genes (IFNa/ß) in infected animals and in cell culture. NSP1 of some strains has been shown to target interferon responsive factor (IRF) 3 for degradation at the proteasome. In contrast, the porcine OSU strain targets another branch of this pathway, the regulator of NK-kappaB, ß-TrCP. It remains unclear whether NSP1 from different host species downregulates the induction of interferon by targeting different host proteins in this signalling pathway or if all NSP1s target a set of proteins which are the common targets irrespective of the host species of origin.

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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