Characterising chicken susceptibility/ resistance markers for avian Influenza virus
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 aim is to understand genetic factors in avian influenza isolates and avian species which alter the disease phenotype, transmission parameters and potential for zoonosis. Use will be made of reverse genetics to dissect the viral genetics and the inbred chicken lines maintained by IAH to understand the role host genetics plays.
Planned Impact
unavailable
People |
ORCID iD |
| Holly Shelton (Principal Investigator) |
Publications
Blumenkrantz D
(2013)
The short stalk length of highly pathogenic avian influenza H5N1 virus neuraminidase limits transmission of pandemic H1N1 virus in ferrets.
in Journal of virology
Chang P
(2015)
Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation.
in Scientific reports
James J
(2016)
Influenza A virus PB1-F2 protein prolongs viral shedding in chickens lengthening the transmission window.
in The Journal of general virology
James J
(2019)
The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NF?B-dependent promoter antagonism in chicken cells.
in The Journal of general virology
Morgan S
(2016)
Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus
in The Journal of Immunology
Peacock T
(2016)
Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape
in Scientific Reports
Peacock TP
(2017)
Variability in H9N2 haemagglutinin receptor-binding preference and the pH of fusion.
in Emerging microbes & infections
| Description | Studies on the virulence determinants of avian influenza have demonstrated that the PA and NS gene segments as well as the PB1F2 are major virulence factors of the virus. We found that full length PB1-F2 contributed to increased apoptosis and pro-inflammation but not to reduced virus replication in swine macrophages, we propose that early apoptosis of swine macrophages limits the spread of avian influenza viruses and that PB1-F2 could play a contributory role in the process. We identified that a small accessory protein, PB1-F2, of influenza viruses acts to prolong viral shedding from infected chickens extending the transmission window. PB1-F2 achieves this by binding to the chicken homologues of MAVS (signaling protein in the type 1 interferon induction pathway) and IKKß (an inhibitor of the NF?B transcription factor (involved in pro-inflammatory signaling following infection) resulting in impairment of the chicken innate immune response to influenza virus infection. . We also found that the sequence of PB1-F2 determined the localisation of the protein in the cell following expression and that the localisation patterns resulted in the differential influences on the antagonism of the two pathways these proteins are involved in. Localisation also governed the stability of the PB1-F2 in the cell. This is new knowledge that contributes to understanding who influenza viruses control the innate response to infection. |
| Exploitation Route | Identification of the role of PB1F2 in virulence provides further opportunities to identify viral determinants |
| Sectors | Agriculture Food and Drink Pharmaceuticals and Medical Biotechnology |
| Description | BBSRC East Bio DTP Studentship |
| Amount | £100,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2017 |
| End | 08/2021 |
| Description | Development of a neuraminase inhibitor |
| Amount | £382,000 (GBP) |
| Funding ID | BB/M023362/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2016 |
| End | 05/2019 |
| Description | Does intra-host dissemination of influenza virus in chickens drive phenotypic changes affecting shed virus characteristics |
| Amount | £6,000 (GBP) |
| Organisation | The Houghton Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 09/2017 |
| Description | The genetic and functional analysis of variation in innate immune genes associated with restriction of influenza virus for chicken lines |
| Amount | £422,383 (GBP) |
| Organisation | Aviagen Group |
| Sector | Private |
| Country | United States |
| Start | 01/2020 |
| End | 03/2021 |
| Description | US Partnering award |
| Amount | £40,000 (GBP) |
| Funding ID | BB/L026554/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2015 |
| End | 07/2019 |
| Description | Understanding the importance of the PI3K pathway in modulating influenza virus replication in chickens and ducks |
| Amount | £100,000 (GBP) |
| Organisation | The Pirbright Institute |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 09/2021 |
| End | 04/2025 |
| Description | Challenge of transgenic chickens with influenza viruses |
| Organisation | Imperial College London |
| Department | Section of Virology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have challenged transgenic chickens with recombinant avian influenza viruses to determine outcome; infectivity, transmission, pathogenicity, dissemination within host. We also processed the samples generated from these animal experiments at The Pirbright Institute. |
| Collaborator Contribution | Imperial College (Wendy Barclay and Mike Skinner) generated recombinant avian influenza viruses for challenge. |
| Impact | This collaboration has resulted in the successful award of a joint grant with imperial college aiming to carry out challenge experiments on novel transgenic chickens to facilitate control of avian influenza virus in the poultry population. BB/S007911/1 - Investigating the role of ANP32A in the replication of avian Influenza virus |
| Start Year | 2018 |
| Description | Gene editing chickens with Roslin |
| Organisation | University of Edinburgh |
| Department | Roslin Institute Transgenic Chicken Facility |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have provided infectious pathogen challenge and infectious pathogen sample processing facilities in this collaboration. We infected the transgenic chickens with avian influenza virus and processed the samples following challenge. |
| Collaborator Contribution | Helen Sang and Mike McGrew at The Roslin Institute (University of Edinburgh) contributed by producing and providing transgenic chickens (Split GFP) for challenge. Expertise in genotype screening the transgenic birds was shared with us. |
| Impact | We have now successfully received a BBSRC responsive mode grant to carry out more transgenic bird challenges with influenza viruses. BB/S007911/1 -Investigating the role of ANP32A in the replication of avian Influenza virus. |
| Start Year | 2018 |
| Description | Janet Daly & Stephen Dunham- PI3K pathway and influenza |
| Organisation | University of Nottingham |
| Department | School of Veterinary Medicine and Science Nottingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Preliminary data was produced by Pirbright using reverse genetics of avian influenza viruses to secure a 50:50 funded PhD studentship that will commence in October 2020 entitled "Understanding the importance of the PI3K pathway in modulating influenza virus replication in chickens and ducks". |
| Collaborator Contribution | Preliminary data was produced by University of Nottingham using PI3K p85 subunit pulldowns to secure a 50:50 funded PhD studentship that will commence in October 2020 entitled "Understanding the importance of the PI3K pathway in modulating influenza virus replication in chickens and ducks". |
| Impact | Funding for a PhD studentship entitled "Understanding the importance of the PI3K pathway in modulating influenza virus replication in chickens and ducks". |
| Start Year | 2019 |
| Description | Suresh Kuchipudi and Janet Daly |
| Organisation | Penn State University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We have hosted a co-supervised PhD student twice at The Pirbright Institute. During these visits we have helped with viral infection of primary cells for analysis of PI3K pathway perturbations and generated new GM influenza viruses to help to understand if the difference in PI3K pathway activity observed between two different avian influenza viruses in avian cells was a result of difference in the NS1 protein. In addition we have provided support to the student regarding the future directions of the project and writing up and presentation of the material. Therefore we have provided reagents, practical expertise and intellectual input. |
| Collaborator Contribution | The collaborators have provided access to data generated in their laboratories and intellectual input to the project. |
| Impact | Publication: doi: 10.1038/srep17999 |
| Start Year | 2016 |
| Description | Suresh Kuchipudi and Janet Daly |
| Organisation | University of Nottingham |
| Department | School of Veterinary Medicine and Science Nottingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have hosted a co-supervised PhD student twice at The Pirbright Institute. During these visits we have helped with viral infection of primary cells for analysis of PI3K pathway perturbations and generated new GM influenza viruses to help to understand if the difference in PI3K pathway activity observed between two different avian influenza viruses in avian cells was a result of difference in the NS1 protein. In addition we have provided support to the student regarding the future directions of the project and writing up and presentation of the material. Therefore we have provided reagents, practical expertise and intellectual input. |
| Collaborator Contribution | The collaborators have provided access to data generated in their laboratories and intellectual input to the project. |
| Impact | Publication: doi: 10.1038/srep17999 |
| Start Year | 2016 |
| Description | TK - School activity - Big Bang at Surrey University (7 Feb 18) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Children from local primary and secondary school attend and access stalls showcasing science and engineering. The Pirbright Institute stall showcases the requirement for improved control of avian influenza viruses with a hands on display of testing and diagnosis of the virus. This sparks questions and discussion about the work at Pirbright in the area of avian influenza viruses. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://nearme.thebigbangfair.co.uk/ |
| Description | TK School activity - Teentech Surrey (15 Nov 17) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Event where upwards of 100 school children aged 11-14 years attend from the regional area and complete STEM based challenges. Influenza virus based challenge set. This event has a measured impact in encouraging children to participate in STEM opportunities particularly girls and those in disadvantaged backgrounds. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.teentech.com/ |