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Regulation of cyclin D1 in coronavirus infected cells

Reference	BB/F019904/1
Principal Investigator / Supervisor	Professor Julian Hiscox
Co-Investigators / Co-Supervisors
Institution	University of Leeds
Department	Inst of Molecular & Cellular Biology
Funding type	Research
Value (£)	373,395
Status	Completed
Type	Research Grant
Start date	01/10/2008
End date	31/03/2012
Duration	42 months

Abstract

Many viruses are now believed to alter host cell processes to facilitate virus replication and progeny virus production. One of the major targets is the cell cycle. We were the first group to show that the coronavirus infectious bronchitis virus (IBV), a disease of economic importance (kills approximately 15,000,000 broilers per year), targeted the cell cycle to enhance viral protein synthesis and progeny virus production. Our data indicated that the principal cellular target for virus infection was cyclin D1 which was almost completely ablated in virus infected cells. This proposal has a number of objectives. It seeks to addresses how and why cyclin D1 is ablated, to identify and characterise the virus protein responsible and to exploit this knowledge in the generation of recombinant viruses that are deficient in interacting with the cell cycle and thus are excellent candidates for growth attenuated recombinant live virus vaccines.

Summary

Viruses are one of the major causes of disease and can lead to significant economic loses in agriculture. Infectious bronchitis virus (IBV), the focus of this grant is no exception and the virus is reported to kill some 15,000,000 poultry annually with associated economic impact. Previous research suggests that many viruses can exploit the cells they infect to help in the growth and production of new viruses. As a result of previous BBSRC funding we have found that IBV also hijacks the host cell to fine tune its infectious cycle. One of the ways it does this is to manipulate what is called the cell cycle by interfering with the very molecules that control this vital cellular pathway. The cell cycle is a mechanism by which normal cells control their growth and production of new cells. The focus of this research proposal is to investigate how IBV interferes with the cell cycle by identify the virus protein(s) responsible and determining the precise mechanism involved. By doing this we aim to develop an in depth understanding of this process that will have broad application to similar viruses and exploit these findings in the development of new vaccines to aid in the control of IBV.

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
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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