Studentship: Analysis of the function of infectious bronchitis virus accessory proteins-towards better vaccines
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
A key area of research in animal disease is the development of more effective and efficient vaccines to prevent infection and transmission. To be able to achieve this objective, a better understanding of virus interaction with host cells and viral pathogenicity factors is required. The avian coronavirus infectious bronchitis virus (IBV) causes respiratory disease in chickens, and some strains cause pathology in the kidneys and reproductive tract. Virus infection results in significant losses to worldwide poultry industries due to reduced meat quality and reduced egg quality and production. Although both live attenuated and killed vaccines are available for IBV, there is poor cross protection between viral strains and the mechanism of attenuation of vaccine viruses is poorly understood. There is a real requirement for improved strategies for IBV vaccine design and understanding molecular aspects of virus replication will provide new insight for this. IBV encodes 5 accessory proteins, including the recently described gene 4b. The function of these accessory proteins is not understood, although they are known not to be required for virus replication in cell culture. The accessory proteins of other coronaviruses including mouse hepatitis virus (MHV) and SARS-coronavirus (SARS-CoV) have been shown to play a role in replication of viral RNA, evasion of host immune responses and modulation of host cell transcription. Although genetically distinct from the accessory proteins from MHV and SARS-CoV, it is possible that the function of the IBV accessory proteins may be similar. The objectives of this project will be to characterise more fully the function of accessory proteins 3a, 3b and 4b on virus replication and identify host cell and viral interaction partners. This will be achieved by virological, molecular biology and proteomic techniques, initially utilising existing recombinant viruses lacking these genes.
Planned Impact
unavailable
Organisations
| Description | Through this project, we have gained further insight into the function of some of the accessory proteins expressed by infectious bronchitis virus. Accessory proteins are not essential for virus replication in cells but often play an important role in disease in the whole animal. We studied 3 accessory proteins and using a pull-down followed by mass spectrometry approach, identified a list of cellular proteins that each interact with. This informed further work to understand the role of the interactions and the impact on the virus. We identified that one of the accessory proteins is able to interact with cellular proteins involved in modulating cellular interferon production, with interactions targeting different stages of the signalling cascade. In addition, we confirmed the expression of a new accessory protein in IBV infected cells. This accessory protein does not appear to play a role in virus pathogenicity but plays a role in induction of cellular stress granules. These results have opened up new research questions, including what is the role of stress granules during IBV replication, how is the pathway modulated and how does this relate to viral shut off of translation. In addition, the data generated to identify cellular interaction partners of the IBV accessory proteins provides a resource for informing future research. |
| Exploitation Route | Data from this project has already been used for further funding applications including successful funding for a follow-on PhD project. In addition, knowledge of the function of IBV accessory proteins may inform design of novel attenuation strategies for development of trial IBV vaccines. |
| Sectors | Agriculture Food and Drink Pharmaceuticals and Medical Biotechnology |
| Description | Findings have formed the basis for further funding applications, including a successful PhD studentship application and establishment of a new collaboration. |
| Sector | Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal |
| Description | Presentation by RH at COST meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | PhD student presented our data at the COST workshop for tackling infectious bronchitis virus. He discussed results and potential collaboration with other scientists. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Presentation by RH at Nidovirus symposium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | PhD student presented our data at the 14th international Nidovirus symposium. He discussed results and potential for future collaboration with other scientists in the field. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Presentation by RH at the Microbiology Society Annual meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | PhD student presented our data at the Annual Microbiology Society meeting, He discussed results and potential for collaboration with other scientists. As a result of this presentation, a new collaboration with N Locker at University of Surrey was established. |
| Year(s) Of Engagement Activity | 2016 |