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Molecular pathogenesis of viral haemorrhagic disease in the pig
Reference
BBS/E/I/00000901
Principal Investigator / Supervisor
Dr Penelope Powell
Co-Investigators /
Co-Supervisors
Institution
The Pirbright Institute
Department
The Pirbright Institute Department
Funding type
Research
Value (£)
5,610
Status
Completed
Type
Institute Project
Start date
01/10/2001
End date
30/09/2004
Duration
36 months
Abstract
We are interested in the molecular basis for the pathogenesis of African Swine Fever virus (ASFV). The virus replicates at high levels in macrophages and vascular endothelial cells and causes haemorrhage and apoptosis in lymphoid tissue (1). We have shown that ASFV inhibits the pigthats response to infection by inhibiting NF?B, the central regulator of genes involved in the innate anti-viral response (2). Remarkably, the virus encodes a homologue of I?B that binds to NF?B, and inactivates the transcription factor (3). We have found that surface expression of MHC Class I is downregulated during ASFV infection of vascular endothelial cells. Expression of the major histocompatibility complex on the surface of cells is important for initiating the immune response. Many viruses have been shown to inhibit expression of MHC Class I to escape immune surveillance (reviewed in (4)). A major focus of the project will be to elucidate the mechanism by which the block in expression of MHC Class I occurs, whether transcriptional, translational or post-translational. The transcription of MHC Class I, for example, is induced by interferons and NFkB, and both responses are blocked by ASFV. We have also shown that ASFV induces apoptosis, with a loss of cytokines and cell surface molecules. We will investigate the effects of ASFV, and the IkB homolog, on the expression of other genes important for the function and survival of vascular endothelial cells.
Summary
unavailable
Committee
Closed Committee - Animal Sciences (AS)
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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