Classical swine fever virus evasion of the innate immune defences
Lead Research Organisation:
THE PIRBRIGHT INSTITUTE
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
The objectives of this project are (1) to understand how CSFV inhibit apoptosis; (2) to investigate the role of viral proteins in pathogenesis and virulence; and (3) to analyse the effects of IFN on CSF infection.
Planned Impact
unavailable
Organisations
People |
ORCID iD |
| Bryan Charleston (Principal Investigator) |
Publications
Doceul V
(2008)
The Npro product of classical swine fever virus interacts with IkappaBalpha, the NF-kappaB inhibitor.
in The Journal of general virology
Johns HL
(2010)
The classical swine fever virus N-terminal protease N(pro) binds to cellular HAX-1.
in The Journal of general virology
Johns HL
(2010)
Classical swine fever virus infection protects aortic endothelial cells from pIpC-mediated apoptosis.
in The Journal of general virology
Reid E
(2014)
Type I and III interferon production in response to RNA viruses.
in Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
Seago J
(2010)
The classical swine fever virus Npro product is degraded by cellular proteasomes in a manner that does not require interaction with interferon regulatory factor 3.
in The Journal of general virology
| Description | We have identified specific proteins produced by viruses that stop cells dying and stop natural antiviral mechanisms being activated. These mechanisms are very important for virus survival, they stop the host controlling the infection and they stop infected cells dying too quickly so that more virus particles can be produced. The new information we have produced can be used in a number of ways. First, we have established that knocking out these proteins results in a virus that is rapidly controlled by the host. We have also shown that expressing the proteins from the virus in cells makes the cells less resistant to virus infection, these cells expressing the virus protein are being used to grow other viruses that we are otherwise unable to grow in cell culture, which may be a great help to identify previously unknown viruses. |
| Exploitation Route | This fundamental work was funded by the institute programme grant as part of the long term strategic funding to understand how viruses that cause major economic losses control the function of cells, cause disease and transmit between animals. This work underpins other externally funded programmes of work to develop new vaccines and understand the immune response in the host species. This work has demonstrated that reducing the capacity of a virus to control the innate immune response and the induce apoptosis results in an attenuated strain that works very effectively as a vaccine. Indeed, we worked in collaboration with a research institute in Germany and a major animal health company to develop a commercial vaccine against bovine viral diarrhoea virus, which is closely related to classical swine fever virus. Also, by studying the interaction of the virus with host cells ex vivo we have identified and characterised in detail rare and highly specialised cells in cattle and pigs (plasmacytoid dendritic cells) that produce antiviral cytokines in response to infection. We have also demonstrated for the first time that both type-I and type-III interferons are produced by these cells and these cytokines can cause immunosuppression in the animals. These findings have a broad application to help understand disease pathogenesis in a range of species including humans plus establish fundamental principles to design effective live attenuated vaccines. |
| Sectors | Agriculture Food and Drink |
| URL | https://www.pirbright.ac.uk/search?keywords=classical%20swine%20fever |