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Understanding the molecular mechanisms and risk factors for highly pathogenic avian influenza evolution and virulence - SE2204

Key issues addressed in this project are:
• Understanding viral genetic determinants of avian influenza virulence and evolution to high pathogenicity
• Understanding the role of quasispecies in highly pathogenic avian influenza (HPAI) evolution in poultry
• Assessing and quantifying the effects of prior immunity on HPAI infection, quasispecies populations and evolution to high pathogenicity (HP)
Highly pathogenic avian influenza is a highly contagious viral disease of poultry and other birds which often results in up to 100% flock mortality. Large outbreaks of HPAI in poultry have an impact that is far reaching and results in substantial losses for governments, farmers and others involved in the production chain.
The highly pathogenic form of avian influenza (AI) likely arises after low pathogenic (LP) H5 or H7 subtype AI is transmitted to domestic poultry from wild birds. It is known that the transition from low to high pathogenicity is genetically characterised by the acquisition of a multi-basic cleavage site in the haemagglutinin (HA) gene of the virus. However, the reason why this predominantly occurs in poultry, and why it only occurs in some instances of LP H7 poultry infection, remains unclear. Not all H7 or H5 LP virus infections of poultry evolve to HP; whether this is due to viral genomic signatures or is influenced by poultry flock size, transmission dynamics or type of poultry is unknown. This key gap in knowledge means that currently all poultry infections with LP and HP H5 and H7 subtype AI viruses are subject to statutory control and potentially flocks will be depopulated due to infection with LP H5 or H7 viruses that may never mutate to cause HPAI. We aim to address elements of this knowledge gap with the objective that eventually a predictive tool can be developed thus enabling an evidence based approach to the control of LP H5 and H7 AI. Ultimately this work will influence policy and have direct relevance to disease control decisions; it will enable better targeting and more efficient use of resources.
This project will build upon previous work (SE0793) that utilised a unique set of viruses and data derived from the Banbury 2008 H7N7 HPAI outbreak to develop a panel of characterised reverse genetics viruses. We will use this cutting edge tool in tandem with ‘next generation’ deep sequencing methodology to detect minor HP variants, in order to investigate the role of quasispecies spectra in the evolution of HPAI viruses and to characterise viral genetic markers that contribute to the high pathogenicity phenotype of H7 viruses. We will complement this work with in vivo experiments to assess the effect of prior immunity on HP infection, evolution and quasispecies spectra.
The information generated will address concerns expressed regarding the control of LP H5 and H7 AI both in the UK and Europe. It will be made publicly available via peer-reviewed publication in scientific journals, conferences and special interest forums such as seminars.
Objective 1. To assess the contribution of influenza quasispecies populations to evolution of highly pathogenic avian influenza
Objective 2. To characterise molecular markers of pathogenicity of avian influenza in avian species using reverse genetics viruses
Objective 3. To assess the effect of prior immunity on HP infection, evolution and quasispecies populations
Time-Scale and Cost
From: 2013

To: 2016

Cost: £536,886
Contractor / Funded Organisations
Veterinary Laboratories Agency (VLA)
Animal Health              
Avian Diseases              
Avian Infectious Influenza              
Plants and Animals