Virus transmission dynamics and the immune response of birds to avian influenza. THIS GRANT IS A SUPPLEMENTATION TO GRANT REF BB/E011691/1
Lead Research Organisation:
The Pirbright Institute
Department Name: Avian Infectious Diseases
Abstract
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Technical Summary
At present H5N1 avian influenza is an animal disease problem under urgent need of control. The widespread occurrence and wide host range of the H5N1 virus poses a serious threat to the human population, potentially leading to the evolution of a human influenza pandemic. Our knowledge of the behaviour of avian influenza viruses in domestic fowl and wild birds is limited. Virus infection dynamics of H7N1 low and high pathogenicity avian influenza viruses and highly pathogenic H5N1 viruses in chickens, turkeys and ducks will be compared. Extensive in-depth sequence analysis of the virus haemagglutinin gene will be undertaken to examine within-host selection of virus variants in each species- avian host range determinants. We also will determine whether in-bred chickens lines show genetic differences in susceptibility to infection and in virus shedding, and whether there are genetic differences in the immune response of the in-bred lines to infection and vaccination- these studies can provide a starting point to uncovering the genetic basis of host resistance to influenza virus infection. The immune response to infection will be studied at tissue level, and protective cellular, humoral and cytokine responses will be defined.
Organisations
People |
ORCID iD |
| Colin Butter (Principal Investigator) |
| Description | A headline discovery from this research is that genetic resistance in chickens determines the outcome of infection and viral transmission dynamics. Using unique, genetically inbred and distinct, lines of poultry we showed that infection with avian influenza virus could either result in local infection and restricted shedding, with no onward transmission of virus, or transmission of virus within the animal and subsequent shedding and transmission to naïve contact animals. Indeed, the restricted transmission of virus within resistant animals appears to be key to the control of subsequent viral transmission. In a preliminary effort at determining which genes contributed to these "resistant" and "susceptible" phenotypes we found that the Major Histocompatibility Complex, a critical group on proteins involved in immune responses, has a significant effect on viral clearance in susceptible animals but was not the determinate factor in resistance or susceptibility. This leaves open the prospect of more detailed genetic mapping to identify the genes responsible and enable poultry producers to incorporate them in their highly structured breeding programmes. As part of this section of work we demonstrated that, unlike in mammals, shedding of virus from the respiratory tract of the bird was insufficient to sustain a chain of infection, while shedding in faeces was wholly sufficient. Whilst this has been hypothesised previously, our study is definitive and the only one to have been conducted with birds housed together and not relying on an artificial barrier to block virus that was shed in faeces. Antibodies play a critical role in the protection of vertebrates from influenza virus. Using an experimental vaccine designed to elicit antibody responses against Avian Influenza Virus we were able to show a distinct pattern of immune responses, depending on the genetic line of bird. However, this did not correlate with the resistance and susceptibility patterns described above, suggesting a different basis for this genetic control. In mammals, cellular immune responses, have also long been known to play a supportive role in clearing influenza infection, killing infected cells before they become viral factories. We developed tools for assaying influenza-specific cellular immune responses in chickens and have demonstrated their importance in this system. Following publication, this technology has now successfully transferred to other laboratories investigating chicken infection and immunity. |
| Exploitation Route | With further work, breeding companies will be able to incorpotate genes responsible for protection into their breeding programmes. |
| Sectors | Agriculture, Food and Drink |
| Title | ELISPOT |
| Description | Development of T cell Elispot technology for enumeration of antigen specific T cells |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | Method has now facilitated other researchers access to an important tool for the analysis of cellular immunity in chickens |
| URL | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334094/ |
| Description | Interviews |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Many television and radio interviews in the area of avian influenza and particularly my research. Both national and local media. |
| Year(s) Of Engagement Activity | 2007,2008,2009,2010,2011,2012,2013,2014,2015,2016,2017,2018 |
| Description | Media |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Various background briefings concerning avian influenza, on and off record, and occasional articles with CBs by-line |
| Year(s) Of Engagement Activity | 2007,2008,2009,2010 |
| Description | Press Conferences |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Sole participant in 2007 Press Conference regards H5N1 hosted at the Foreign Press Association, London. Objective was to provide clarity regards the state of the H5N1 outbreak in Bernard Matthews Turkey farm. Specific interest regarding international implications. Panel member in 2013 Press Conference Hosted by the Science Media Centre to provide the media with information regards H5N7 transmitting to and killing people. |
| Year(s) Of Engagement Activity | 2007,2013 |