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African swine fever virus immunomodulatory genes - SE1508

Description

The main objective is to identify and study the function of African swine fever virus encoded proteins involved in evasion of the host immune system. Three proteins will be studied, A238L, CD2v and j4R. We have already shown that the A238L protein inhibits calcineurin phosphatase activity and activation of the NFkB transcription factor. We will now study its effect on macrophage gene expression to identify host immunomodulatory genes whose expression is altered as a consequence of A238L expression. The CD2v protein cytoplasmic tail binds to a cellular protein that links cell surface receptors to the cytoskeleton (SH3P7). We will investigate the effect of CD2v on signal transduction pathways in macrophages. The j4R protein binds to a transcriptional co-activator (alpha-NAC). We will investigate whether this interaction interferes with the ability of alpha-NAC to function as a transcriptional co-activator with the c-Jun and ATF4 factors. As a consequence transcriptional activation of genes dependent on these factors may be inhibited.

The benefits from the work will be a better understanding of virus host interactions which will aid vaccine development. Other benefits will be increased knowledge of pathways involved in regulating pig immune responses and development of reagents which could help research on other diseases. The results will be made available to the scientific community through publication and presentation at meetings. Knowledge and reagents from this project will help to direct future research on ASFV and possibly other diseases.

Objective

1. Compare expression of immunomodulatory genes in macrophages infected with wild type ASFV and ASFV from which the A238L gene has been deleted to identify genes whose transcription is altered by the ASFV A238L protein.
2. Investigate the effect of the ASFV CD2v protein on signalling pathways in macrophages.
3. Determine the effect of the ASFV j4R protein on transcriptional activation mediated by the alpha-NAC transcriptional co-activator.
Project Documents
• Final Report : African swine fever virus immunomodulatory genes   (79k)
Time-Scale and Cost
From: 2000

To: 2003

Cost: £211,911
Contractor / Funded Organisations
Institute for Animal Health (BBSRC)
Keywords
African Swine Fever              
Animal Diseases              
Animal Health              
Biotechnology              
Plants and Animals              
Vaccines              
Fields of Study
Animal Health