Understanding the mechanism of influenza A virus PB1-F2 immune signalling antagonism
Lead Research Organisation:
University of Edinburgh
Department Name: The Roslin Institute
Abstract
Avian influenza poses a major threat to animal health and food security. For instance, H5N1 influenza has been responsible for the deaths of over 300 million chickens since 2003. A better understanding of virus interactions with the avian host is therefore crucial to improve control strategies. This project will focus on the role of accessory proteins encoded by the virus genome. These proteins are non-essential for virus replication in vitro, but can modulate pathogenicity in vivo [1, 2]. PB1-F2 is a small accessory protein with a role in suppressing the inferferon response that is more highly conserved in avian than mammalian influenza isolates. We have recently shown that depending on virus strain, PB1-F2 can suppress innate immune signalling, decrease pathogenicity and lengthen viral shedding, extending the transmission window in chickens [2]. Our hypothesis is that influenza A virus PB1-F2 proteins have evolved to invoke suppression of innate signalling responses in avian hosts through variable mechanisms and that these differences partially explain pathogenicity. To interrogate this hypothesis the following questions will be studied;
1. What are the viral genetic determinants in PB1-F2 that influence the ability to antagonise the type I IFN or NF-kb (pro-inflammatory) signalling pathways?
What are the differences in the cellular interactome for PB1-F2 proteins that utilise these different mechanisms? How important are the prescribed functions of a PB1-F2 protein during infection of poultry within a defined viral genetic constellation?
1. What are the viral genetic determinants in PB1-F2 that influence the ability to antagonise the type I IFN or NF-kb (pro-inflammatory) signalling pathways?
What are the differences in the cellular interactome for PB1-F2 proteins that utilise these different mechanisms? How important are the prescribed functions of a PB1-F2 protein during infection of poultry within a defined viral genetic constellation?
People |
ORCID iD |
Paul Digard (Primary Supervisor) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
BB/M010996/1 | 30/09/2015 | 31/03/2024 | |||
1991999 | Studentship | BB/M010996/1 | 31/08/2017 | 30/11/2021 |
Description | GAVI 2020 BSI involvement |
Geographic Reach | Europe |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
URL | https://www.immunology.org/publications/immunology-news/immunology-news-september-2019/bsi-policy-wo... |
Description | Roslin Institute-Pirbright Institute |
Organisation | The Pirbright Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am a joint student between two research institutes. I have split my time between sites and worked with both research groups. |
Collaborator Contribution | I have a supervisor from each institute and half my funding comes from the Pirbright Institute |
Impact | N/A |
Start Year | 2017 |
Description | Roslin Institute-Pirbright Institute |
Organisation | University of Edinburgh |
Department | The Roslin Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am a joint student between two research institutes. I have split my time between sites and worked with both research groups. |
Collaborator Contribution | I have a supervisor from each institute and half my funding comes from the Pirbright Institute |
Impact | N/A |
Start Year | 2017 |
Description | Cheltenham Science Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | As part of The Pirbright Institute team, I ran an epidemiology based activity for small groups and helped on the stall at Cheltenham Science Festival |
Year(s) Of Engagement Activity | 2019 |
Description | EBSOC workshop |
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 | I helped develop and deliver practical lab experience workshops to high school students in the Midlothian regional at the University of Edinburgh EBSOC lab. |
Year(s) Of Engagement Activity | 2018,2019 |
URL | https://www.roslininnovationcentre.com/outreach |
Description | Leaders in Science |
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 | I worked as part of a team to introduce advanced scientific concepts to high school children and support the students presenting to primary school children on their own |
Year(s) Of Engagement Activity | 2019 |
URL | http://www.leadersinscience.org/ |
Description | Skype a Scientist |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Schools |
Results and Impact | Through Skype a Scientist, I was matched with classrooms in the US. I skyped the schools, giving a short introduction and then a prolonged Q&A session to children of varying ages. |
Year(s) Of Engagement Activity | 2019,2020 |
URL | https://www.skypeascientist.com/ |