Understanding animal health threats from emerging H5 high pathogenicity avian influenza viruses
Lead Research Organisation:
University of Nottingham
Department Name: School of Veterinary Medicine and Sci
Abstract
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Technical Summary
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.
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.
| Description | We developed a cell-based and egg-based system to compare virus replication rates across species and different virus strains. This could be applied to identify which emerging virus strains merit further attention and to predict disease outcomes for different avian species. We have evidence to indicate that human neuronal cells are susceptible to highly pathogenic avian influenza H5N1 virus infection. |
| Exploitation Route | We need to continue with ongoing studies to come to a more complete set of findings. |
| Sectors | Agriculture Food and Drink Healthcare |
| Description | Flu:Trailmap "Transmission and risk of avian influenza: learning more to advance preparedness" |
| Amount | £279,470 (GBP) |
| Funding ID | BB/Y00700X/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2023 |
| End | 04/2025 |
| Title | in ovo model of infection |
| Description | The use of an in vitro culture system to evaluate virus replication across species is limited by cell line or primary cell availability. We propose using embryonated eggs (below the 2/3 incubation period) to evaluate virus replication rates, enabling comparison across relevant species with and without cell lines (e.g. chicken, ducks, game birds) and across breeds. |
| Type Of Material | Biological samples |
| Year Produced | 2023 |
| Provided To Others? | No |
| Impact | This model may be used to identify species which may be more susceptible to emerging HPAI strains and identify emerging virus strains which may be a threat to commercial species. |
| Title | Airborne transmission of human-isolated avian H3N8 influenza virus between ferrets |
| Description | Genetic variation data derived from ferret transmission experiments of avian H3N8 influenza viruses. Supplementary Dataset 1. Genetic variation data derived from ferret transmission experiment of HN/4-10 virus. Supplementary Dataset 2. Genetic variation data derived from ferret transmission experiment of CS/1000 virus. Supplementary Dataset 3. Genetic variation data derived from ferret transmission experiment of CK/FE12 virus. Supplementary Dataset 4. Genetic variation data derived from ferret transmission experiment of CK/F0316 virus. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | This papers identified a new zoonotic threat of avian H3N8 virus to humans. |
| URL | https://zenodo.org/record/8191338 |
| Title | SRSF5-mediated alternative splicing of M gene is essential for influenza A virus replication: a host-directed target against influenza virus. |
| Description | Peer reviewed paper. https://doi.org/10.1002/advs.202203088 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | The paper describes a novel host factor SRSF5 that facilitates influenza virus replication. |
| URL | https://onlinelibrary.wiley.com/doi/10.1002/advs.202203088 |
| Description | Collaboration with the APHA to evaluate in vitro/in ovo infection models and species specific responses to virus infection |
| Organisation | Animal and Plant Health Agency |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | UoN designed the in vitro infection model to characterise past and emerging influenza viruses across avian species (duck and chicken), we conducted the initial experiments using low pathogenic avian influenza viruses (LPAI) as a basis of comparison for the high pathogenic avian influenza viruses (HPAI). In order to compare host specific responses to HPAI or LPAI infection in chicken and duck cells, UoN undertook next-generation sequencing to compare the transcriptome and identify host factors/processes which may account for differences in disease outcomes across species. |
| Collaborator Contribution | The APHA provided the facilities and technical support in generating samples using highly pathogenic avian influenza virus strains which were passed on to UoN for further processing. |
| Impact | The data generated from this collaboration will contribute to a publication evaluating the application of an in ovo model to characterise emerging viruses (undergoing internal review) and a paper examining species specific differences in commitment to apoptosis (work ongoing). Data collected as a result of this collaboration was presented at the UK-China Avian Flu Control Workshop and Flu-Trail Map Workshop. |
| Start Year | 2022 |