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Award details
The role of innate and adaptive immune responses in immunity to bovine viral diarrhoea virus
Reference
BBS/E/I/00000791
Principal Investigator / Supervisor
Professor Bryan Charleston
Co-Investigators /
Co-Supervisors
Institution
The Pirbright Institute
Department
The Pirbright Institute Department
Funding type
Research
Value (£)
943,640
Status
Completed
Type
Institute Project
Start date
01/04/2000
End date
31/03/2003
Duration
36 months
Abstract
Studies to examine the cytokines generated during immune responses to BVDV and to determine the effect of BVDV on antigen-presenting cell functions will be closely inter-linked. More detailed studies of the cytokines generated during the early stages of infection will be conducted by examining samples of serum and cells ex viva as well as cells stimulated in vitro with defined BVDV antigens. These studies will utilise a variety of assays for detection of cytokine expression both at the RNA and protein level. The studies will aim to identify which cell types are responsible for producing cytokines that are upregulated. T cell responses for unrelated antigens will be studied both in vitro and in vivo during acute BVDV infections to determine how BVDV alters the responses. Studies of the effects of infection with BVDV on the capacity of monocytes and dendritic cells to function, as antigen-presenting cells will also focus on analyses of changes in cytokine expression induced by infection. Current CD4+ T cell epitope mapping will be extended to additional MHC haplotypes with the aim of building up a picture of the dominant sites recognised by CD4+ T cells in the E2 and NS3 proteins. Class II-specific monoclonol antibodies, together with transfected cell lines expressing defined DR and DQ genes, will be used to determine whether the responses are restricted predominantly by DR or DQ. By comparing the sequences of dominant T cell recognition sites in different viruses and testing synthetic peptides for T cell recognition it will be possible to determine the extent to which the responses are strain-specific and assess whether there is evidence for T cell-induced mutation in the virus. The role of individual viral proteins in immunity will be investigated in two ways; First, using DNA constructs expressing different viral proteins and second, employing infectious cDNA clones of the virus incorporating defined mutations.
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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