Award details

Identification of innate and adaptive immune responses that restrict ASFV replication

Reference	BBS/E/I/00001439
Principal Investigator / Supervisor	Dr Geraldine Taylor
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	395,832
Status	Completed
Type	Institute Project
Start date	01/07/2009
End date	31/03/2012
Duration	33 months

Abstract

Dendritic cells (DC) are central to the induction and control of immune responses and are an important link between innate and adaptive immunity. We will characterise the interaction of African swine fever virus (ASFV) with conventional DC and plasmacytoid DC and determine how these interactions modulate the function of lymphocytes. Evidence suggests that the innate host interferon (IFN) response is important in determining the outcome of infection with ASFV. IFNa treatment of virus susceptible cells leads to a significant reduction in virus titres and ASFV isolates of differing virulence may vary in their ability to replicate in the presence of porcine IFNa. Although IFN-inducible porcine genes limiting ASFV replication have not been defined, a human IFN-regulated gene, MxA, can effectively inhibit ASFV replication in vitro. Preliminary studies suggest that porcine Mx1, the porcine homolog of MxA, may act in a similar way to MxA. We hypothesise that IFN-regulated genes are required to limit ASFV replication and that virus virulence is linked to the ability of the virus to overcome the anti-viral state. We will identify the porcine IFN-regulated genes that are required to inhibit ASFV replication; determine any differences in IFN-regulated genes in cells from genetically distinct swine; and determine what effect ASFV infection has on the anti-viral state. The presence of ASFV-specific CD4hiCD8+perforin+ memory cells that produce IFNg in pigs vaccinated with avirulent ASFV correlate with protection against certain virulent strains of ASFV but by unknown mechanisms. We will investigate the ability of porcine IFNg to restrict ASFV replication and other molecules produced by immune ASFV-specific T cells that may mediate protection. In addition, we will investigate the ASFV proteins recognised by IFN gamma producing CD8+ T cells in pigs infected with ASFV and determine the influence of porcine MHC class I genotype on the antigenic specificity of the CD8+ T cells.

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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