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?

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M010996/1 01/10/2015 30/09/2023
1991999 Studentship BB/M010996/1 01/09/2017 31/08/2021 Elizabeth Billington
 
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/