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Investigations of susceptability, host tropism and responses to avian influenza infection in galliformes. - SE0792

This proposal aims to provide strategic research to address key gaps in the scientific evidence base which have been used to directly inform control and surveillance strategies in response to outbreaks of notifiable avian influenza (NAI). A wide spectrum of clinical presentation, both related to host and AI virus (AIV), raises questions which differ between outbreaks. Control and surveillance strategies need to be adapted to each outbreak scenario, and will be dependant on the poultry host and AIV strain. Introduction of NAI from wild to domestic waterfowl and /or to galliformes is a key pathway for introduction of AIV to domestic poultry. This project aims to address the mechanisms and modes of transmission whereby low pathogenicity (LP)NAI viruses spread into farmed galliformes, and potentially lead to host adaptive changes in the AIV which may result in mutation to highly pathogenic (HP)NAI. Mechanisms that influence these adaptive changes can help define risk pathways. Data from this project will inform more robust risk assessments and pertinent control measures, and inform improved biosecurity practices for industry.

There have been a disproportionately large number of separate outbreaks of HPNAI in GB. Of the 26 primary outbreaks of HPNAI reported throughout the World since 1959, 5 (19.2%) have been in GB: H5N1 in 1959, H7N3 in 1963, H7N7 in 1979, H5N1 in 1991 and H7N7 in 2008. There were also two introductions of Asian lineage HPNAI H5N1 virus into poultry in GB in 2007. This H5N1 HPNAI virus also caused an outbreak in quarantine birds in 2005, and on two occasions (2006 and 2008) was detected in wild birds in GB. LPAI outbreaks have occurred in GB poultry in 2006-2007 due to H7 NAI viruses, and there an outbreak of H6N1 occurred in 2009. All these cases resulted in considerable financial losses due to disease, stamping out, disease investigation, surveillance and trade embargos. Elsewhere in Europe, both LPNAI and HPNAI viruses continue to be isolated regularly from wild birds and both galliformes and anseriformes poultry.

This proposal addresses three key questions concerning AI in poultry. Firstly, to investigate the routes and mode of spread of H5 and H7 subtype LPAI viruses from anseriformes to galliformes. Factors responsible for transmission from waterfowl to galliformes will be investigated, where transmission pathways will be more clearly defined. This will advise appropriate intervention strategies during NAI outbreaks. Outbreak investigations continue to pose questions about NAI origin and spread, this being a knowledge gap that has exposed uncertainty in informing policy.

Secondly, the effect of prior exposure to LP AIVs upon challenge with HPNAI viruses will be studied. Past experimental work has indicated that chicken infections with some H1 AIVs may provide some protection against subsequent challenge with H5 HPNAI viruses. Initial infection of galliformes and anseriformes with non-H5 LPAI viruses will be followed by Asian lineage H5N1 HPNAI challenge to determine any effects relating to clinically overt disease and AIV shedding. Galliformes will also be infected with pandemic H1N1 (2009) influenza virus (H1N1v) to be similarly followed by H5N1 HPNAI challenge. Two separate occurrences of H1N1v field infection have already occurred in turkeys. This raises questions regarding the impact such infection may have upon detection of other more clinically manifest viruses, such as H5N1 HPNAI. Partial protection due to prior LPAI exposure may confuse diagnosis and result in silent spread of HPNAI. Such information would have important consequences for decisions regarding continued high value passive surveillance techniques, while directing appropriate surveillance methods for prior immunity to other AIVs, including H1N1v.

Thirdly, we will utilise in ovo models to study host-pathogen interaction. Such systems are commonly established in AI diagnosis, but will be further exploited to dissect mechanisms whereby AIVs adapt to different hosts. This offers opportunities to evaluate stages in host adaptation and the events that may lead ultimately to the emergence of HPNAI. These systems would offer ease of use and facilitate greater analysis not possible with in vivo studies. Such approaches would be validated against targeted in vivo studies in poultry.

The study provides avenues for greater diversification of the funding base for research conducted by VLA Avian Virology, extending informal collaborations and opportunities with the academic sector, enriching and enhancing skills that may be available. These are already ongoing with colleagues at Nottingham University School of Veterinary Medicine and Sciences (NU). Added value will be provided to the project through a separate but joint-funded (VLA and NU) PhD initiative to study pathogenesis and host response of AI infections. Pathology expertise at VLA has already contributed to the observation of pathological changes in different hosts infected with diverse AIVs. The project will allow VLA to maintain and build expertise in the area of virus-host interactions, so enhancing our understanding of how these may influence the course of AI outbreaks.
The project’s three Objectives are to investigate factors that effect the manifestation of avian influenza in different host species, taking into account different host and viral factors:
1. Investigate the modes of transmission and the impact of host switching from waterfowl to galliformes on the virus.
2. Determine the consequences of prior immunity to avian influenza viruses and pandemic (H1N1) 2009 influenza virus upon subsequent HPNAI challenge in poultry.
3. Evaluate the use of in ovo models for investigating factors which influence host adaptation and possible mutation to virulence.
Project Documents
• EVID4 - Final project report : SE0792 evid4 final report final   (734k)
Time-Scale and Cost
From: 2010

To: 2014

Cost: £594,710
Contractor / Funded Organisations
Veterinary Laboratories Agency
Animal Diseases              
Animal Health              
Avian Diseases              
Avian Infectious Influenza              
Plants and Animals              
Fields of Study
Animal Health