Project Number: 6040-32000-081-000-D
Project Type: In-House Appropriated
Start Date: Oct 1, 2021
End Date: Sep 30, 2026
1. Characterize the ecology, epidemiology, and pathogenesis of emerging avian influenza viruses with a focus on the One-Health concept. 1.A. Characterize the pathogenesis of new and variant avian influenza virus (AIV) isolates and determine quantifiable species-specific transmission parameters of AIVs for modeling and outbreak preparedness. 1.B. Conduct the molecular characterization of new and variant AIVs including phylogenetics, and network analysis. 1.C. Examine novel or emerging viruses that may have an impact on poultry health or where poultry pathogens affect public health. 1.D. Assess the inter- and intra-species transmission dynamics of LPAI viruses, which will also contribute to investigating mechanisms and pathways of intra-host virus evolution. 1.E. Investigate determinants of virulence and mechanism behind increased pathology seen with some LPAI virus subtypes. 2. Elucidate the host-pathogen interactions of avian influenza virus infections. 2.A. Investigate virus-specific factors and viral molecular markers associated with infectivity, pathogenicity, and transmissibility of influenza viruses in avian species including virus tissue tropism and replication. 2.B. Investigate host-specific factors associated with the infectivity, pathogenicity, and transmissibility in different avian species of current and emerging influenza viruses including species, breed, age, and physiological state of the bird, and concomitant infections. 2.C. Characterize the innate and adaptive immune response to avian influenza virus infection in different avian models that are either susceptible, tolerant, or resistant to infection. 3. Develop intervention strategies to effectively control avian influenza viruses and contain disease outbreaks. 3.A. Improve virus control and recovery strategies by producing data on the environmental ecology of AIV. 3.B. Evaluate and improve existing and new diagnostic tests and testing strategies for avian influenza virus surveillance, detection, and recovery from disease outbreaks. 3.C.1. Evaluate existing or develop new vaccine platforms and strategies designed to rapidly control and prevent avian influenza virus outbreaks in the various components of poultry production. 3.C.2 Investigate the impact of immunosuppressive viruses on the efficacy of AIV vaccines in chickens. 3.D. Characterize the effect of vaccine induced immunity on virus evolution. 3.E. Utilize precision engineering of the chicken genome to develop genome edited poultry with increased resistance to avian influenza virus. 3.F. Identify correlates of vaccine protection in avian species, including different breeds and ages. 3.G. Determine mechanisms and immune-system-wide effects of vaccines with rapid onset of broadly protective immunity. 3.H. Determine the role of vaccines in driving escape mutations and how to prevent them.
These objectives include a combination of basic and applied research that will generate knowledge and help develop tools to improve our ability to prevent and control avian influenza virus (AIV). These research goals are highly interrelated and will be accomplished with similar tools and approaches (Figure 1); thus, experiments will often contribute to more than one objective. The first objective includes the characterization of new strains of AIV and other viruses, which constantly emerge in nature. The second objective complements the first with a more in-depth focus on the specific viral and host factors that contribute to host adaptation, transmission, and virulence. The third objective will improve current practical intervention strategies including diagnostics, vaccines, development of AIV resistant poultry, and will enhance our understanding of the ecology of AIV in poultry. For objectives 1 and 3: Utilizing sequencing in vitro and in vivo models, low pathogenic avian influenza virus (LPAIV) will be tested to identify how host range is determined and markers for virus pathogenicity identified. Multiple types of immune system models and reagents with in vitro models and in vivo models will be used to characterize the immune response to LPAIV viral infection and vaccines.