How the Vaccinia virus protein C6, inhibits IFN-gamma signalling
Lead Research Organisation:
University of Cambridge
Department Name: Pathology
Abstract
Theme: World-Class Underpinning Bioscience
The Vaccinia virus protein C6 has been shown to inhibit the induction of IFN-gamma, a critical cytokine of the immune response. This project would sort to understand the molecular mechanism by which C6 can inhibit this pathway, both improving our understanding of virus/host interactions and fundamental cell biology processes.
ENWW:
- Project has the potential to utilise high throughput proteomics/genomics though which I can apply bioinformatics analysis to better understand the changes in gene expression/ virus host interactions during virus infection.
The Vaccinia virus protein C6 has been shown to inhibit the induction of IFN-gamma, a critical cytokine of the immune response. This project would sort to understand the molecular mechanism by which C6 can inhibit this pathway, both improving our understanding of virus/host interactions and fundamental cell biology processes.
ENWW:
- Project has the potential to utilise high throughput proteomics/genomics though which I can apply bioinformatics analysis to better understand the changes in gene expression/ virus host interactions during virus infection.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011194/1 | 01/10/2015 | 31/03/2024 | |||
| 1804930 | Studentship | BB/M011194/1 | 01/10/2016 | 27/01/2022 | Callum Talbot-Cooper |
| Description | The research has lead to the discovery of a novel inhibitor of the anti-viral response encoded by the vaccinia virus. This novel inhibition binds to cellular protein STAT1 and the co-structure of the viral and cellular protein has been solved using crystallography. We have discovered that mechanistically, the viral protein blocks the activation of STAT1 by preventing the recruitment of STAT1 to the interferon receptor. We also discovered a viral protein from Nipah virus that binds STAT1 harbours a sequence similar to that found in vaccinia virus demonstrating these evolutionary distinct viruses have evolved similar mechanisms to inhibit the pathway. Finally, mouse work has demonstrated that a vaccinia virus lacking this novel inhibitor has reduced virulence. |
| Exploitation Route | Vaccinia virus has been utilised for a vaccinia based vector for other disease's other than smallpox. These vectors still contain the novel anti-viral inhibitor. Deletion of this gene from these vectors may be found to enhance the immunogenicity of these vaccine vectors thereby improving their use. Additionally, other viruses may have evolved similar strategies to inhibit the anti-viral response. The regents made during this project will help others identify anti-viral inhibitors from other viruses. The information gained from the co-structure can help inform the development of small molecular inhibitors targeting STAT1 in diseases whereby STAT1 is deregulated |
| Sectors | Pharmaceuticals and Medical Biotechnology |