Understanding animal health threats from emerging H5 high pathogenicity avian influenza viruses

High pathogenicity avian influenza virus (HPAIV) is a significant burden on animal health, with a risk of human infection that demands continuous monitoring and control globally. Incursions of HPAIV into the UK and Europe have increased significantly in the last two winter seasons. During the 2020/21 season, 26 infected poultry premises (IPs) were detected across the GB (24 IPs) and NI (2 IPs) with over 300 wild birds testing positive, a record outbreak season at that time. The 2020/21 outbreak was dominated by the detection of the HPAIV H5N8 subtype, although an undercurrent of alternative H5 based subtypes was detected including H5N5 in poultry, and H5N1 and H5N3 also being detected in wild birds. This season was then followed by a significant escalation in cases due to new incursions during 2021/22, with over 100 IPs across the UK, all caused by H5N1 HPAIV. During 2021/22, more than 800 wild birds have tested positive for H5N1 virus, with just a single wild bird detection of H5N8. This project targets this extreme emergence of HPAIV in the UK (and beyond), to improve our understanding of HPAIVs to help mitigate incursions and refine approaches to future prevention strategies.

Work-package (WP1) aims to improve the understanding of HPAIV transmission dynamics for these viruses in both wild birds and domesticated poultry. By undertaking biological sampling and data analysis we will design more effective, risk-based surveillance programmes and model interactions at wild bird and poultry interfaces, defining geographical sites and wild bird populations of high risk, and linkages to farm incursions. Outputs will enable a greater understanding of the reservoir of infection, wild waterfowl, as well as factors that drive incursion of disease from this reservoir into the poultry sector.

WP2 aims to assess antigenic diversity across the HPAIVs detected in the UK in recent years in context of co-circulating low pathogenicity AIVs, in the absence of disease, both in wild waterfowl and poultry. The sequential emergence of HPAIVs suggests that prior immunity from 2020/21 to H5N8 virus was insufficient to prevent emergence and dominance of H5N1 during 2021/22. This WP will define how antibody responses to different virus surface proteins impact upon the potential of virus emergence. This feature of infection will utilise post-infection antisera derived from natural and experimental infection to study immune escape. Areas of the virus that are identified as being important in the emergence of escape mutants will be further investigated to define where flex exists within viral proteins targeted by the host immune response. This will enable focused studies that will help develop our understanding of what factors might influence future mitigation strategies.

Finally, factors that drive differential disease outcomes, outside of the viral surface proteins, will be assessed in WP3. Here, novel systems will be developed to assess viral infectivity and host range which in turn will enhance our understanding of virus-host interactions and define the role of internal viral proteins, critical to viral replication, driving virus diversity and emergence with consequent disease outcomes. WP3 will utilise outputs from WP1 and WP2 to examine the mechanisms that drive the emergence of virus variants, enabling differential adaptation to different hosts. Experimental systems that enable individual components of the viral replicative machinery to be assessed and compared will be developed, utilising our ability to generate viruses in the laboratory to defined genetic specification. Minimal infectious doses and related growth kinetics will be assessed to refine work in animal models. Utilising expertise from across the UK in different experimental systems, with access to a range of laboratory facilities, the partners will link across WPs to generate impactful outputs to enhance our understanding of these emerging pathogens.

The UK poultry industry is experiencing severe socio-economic damage and threats from high pathogenicity avian influenza viruses (HPAIVs) H5Nx of clade 2.3.4.4. These viruses pose zoonotic infections risks. The rapid evolution of these viruses is modulating their biological behaviour (epidemiology, host-range, transmission, and pathogenesis) in different avian species. To determine potential risks and improve controls against these emerging and re-emerging viruses requires a comprehensive knowledge base about the nature of prevailing viruses, and an integrated cross-disciplinary approach to studying virus ecology and epidemiology based on understanding virus/host interactions, and the genetic determinants of virulence, transmissibility and antigenicity in wild birds/poultry.

This project will investigate how contemporary H5Nx HPAIVs acquire adaptive changes to increase fitness within domestic and wild avian populations. We will define viral and host factors that potentially contribute to increased transmissibility, persistence, and pathogenicity in wild birds and those that enhance their potential to disseminate and manifest disease in poultry. Evolutionary changes drive virological, immunological and zoonotic infection potential of these viruses therefore, our understanding of environmental and molecular correlates required or associated with successful evolution, immune escape, dissemination and maintenance of HPAIVs via migratory populations of wild birds will be developed. Furthermore, we will define molecular markers for successful interspecies transmission and fitness in poultry with severe clinical outcomes. The will provide insights for assessing threats from new and emerging strains, enabling national and international agencies to design and execute contingencies as part of risk mitigation and disease control. This will provide vital information when considering how to invest scarce resources for surveillance design aimed at early warning of the threat.