Characterising chicken susceptibility/ resistance markers for avian Influenza virus

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

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.

Publications

10 25 50

 
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 09/2017 
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 05/2016 
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 Unknown
Start 10/2016 
End 09/2017
 
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 08/2015 
End 07/2019
 
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 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/