Virus transmission dynamics and the immune response of birds to avian influenza.

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

The global spread of H5N1 highly pathogenic avian influenza viruses and their ability to infect not only birds but humans emphasises that human and animal health are unavoidably linked. At present avian influenza remains an animal disease problem under urgent need for control but control in birds will also reduce the potential for a human influenza pandemic. Our knowledge of the behaviour of avian influenza viruses in domestic fowl and wild birds is limited. This proposal poses some fundamental questions that address how the easily the virus can infect chickens, turkeys and ducks; how much, and for how long, virus is shed following infection in each species; and how avian influenza virus infection is controlled by the immune response of birds. Fundamental studies of this type will be critical to the design and implementation of control measures in the short term and the long term.

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.
 
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 Once further mapping of the the relevant genes is achieved the poultry breeding companies would be able to breed resistance into their production birds. We intend to apply for funding for collaborative efforts to pursue this work.
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