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ARS Home » Southeast Area » Athens, Georgia » U.S. National Poultry Research Center » Endemic Poultry Viral Diseases Research » Research » Research Project #441471

Research Project: Systems Biology Approaches to Develop Medical Countermeasures to Detect, Prevent, and Control Poultry Production Viral Diseases

Location: Endemic Poultry Viral Diseases Research

2022 Annual Report

1. Elucidate host-pathogen interactions of avian reovirus and develop veterinary countermeasures to detect, prevent and control the poultry production viral disease. 1.1. Identify reovirus determinants of virulence associated with arthritis and tenosynovitis in poultry production. 1.2. Develop new diagnostic platforms for the early detection of avian reoviruses on poultry farms. 1.3. Develop new vaccine strategies to prevent and control avian reoviruses on poultry farms. 2. Elucidate host-pathogen interactions of infectious bursal disease virus and develop veterinary medical countermeasures to detect, prevent, and control the poultry production viral disease. 2.1. Apply systems biology approaches to characterize host-pathogen interactions associated with infectious bursal disease virus strain variation, immunosuppression, and pathogenesis. 2.2. Develop genomics and immune intervention strategies to prevent and control infectious bursal disease virus (IBDV), including emerging very virulent and variant IBDV strains.

Avian reovirus (ARV) and infectious bursal disease virus (IBDV) are economically important pathogens of poultry that are endemic in the U.S. and threaten poultry production. ARVs cause viral arthritis syndrome/tenosynovitis in young chickens and turkeys, but the full extent of clinical disease is unclear. IBDV-infected flocks have high mortality, poor feed conversion ratio, and decreased meat production. There are major knowledge gaps for both viruses with respect to tools for control and prevention, as well as a lack of basic knowledge of the viral pathogenicity and host immune response address these gaps, our research on ARV will focus upon 1) developing an ARV whole-genome sequence database and an antigenic cross-reactivity database to be used for antigenic cartography and vaccine development; 2) exploring the ability of ARVs to suppress the host antiviral innate immune response; and 3) exploring the use of herpesvirus of turkeys (HVT) and Newcastle disease virus (NDV) as delivery vectors for multivalent ARV sigma C antigen-based vaccines. For IBDV, we plan to 1) develop a reverse genetic system to investigate the role of IBDV virus protein 2 (VP2) gene in virulence determination; 2) create an IBDV disease/challenge model to study disease pathogenesis and vaccine protective efficacy; 3) investigate host innate immunity and genetic resistance to IBDV; and, finally, 4) develop NDV vectored in ovo dual vaccines against NDV and IBDV. The outcome of this project will include 1) basic knowledge of the viral pathogenicity and innate immunity against ARV and IBDV; 2) knowledge to guide producers in breeding IBD-resistant chicken lines; 3) disease models to assist in pathogenesis studies and vaccine evaluation; and 4) new ARV and IBDV vaccines to benefit the poultry meat and egg production industries and the American consumer.

Progress Report
The previous Projects: Intervention Strategies to Prevent and Control Enteric Diseases of Poultry, 6040-32000-073-000D, and Intervention Strategies to Prevent and Control Immunosuppressive Viruses of Poultry Associated with Secondary Pathogen Infections, 6040-32000-075-00D, were terminated on 01/02/2022. In pursuit of Objective 1 in the new project, ARS researchers in Athens, Georgia, identified partners and established collaborations with academics, including academic laboratories at the University of Georgia in Athens, Georgia, and Auburn University in Auburn, Alabama. ARS researchers also established Material Transfer Agreements with these same organizations and laboratories and have received samples of avian reovirus isolates from our partners at the University of Georgia. In support of Sub-objective 1.3., ARS researchers have designed and synthesized the insert sequences for a recombinant herpesvirus of turkeys, which will provide multi-valent protection against multiple strains of avian reovirus. Infectious bursal disease virus (IBDV) remains a major problem for poultry farmers globally, causing substantial economic losses. IBDV-induced immunosuppression results in vaccine failure, making them susceptible to other diseases. The severity and clinical presentation of the disease depend on the immune status of the chicken, age, genetic background, and virulence of the infecting virus strain. Chickens infected between the age of 3 and 6 weeks develop the most severe clinical infectious bursal disease. To evaluate the pathogenicity of IBDV strains circulated in the U.S., ARS researchers in Athens, Georgia, collected some highly virulent IBDV strains isolated in California, U.S. Currently, these IBDV strains are being propagated in chicken embryos. Once enough of the virus is collected/propagated, we will investigate the molecular determinants of the virus on host adaptation, immunosuppression, transmission, and virulence. Infectious bursal disease virus (IBDV) causes a highly contagious immunosuppressive disease in chickens with severe economic losses to the poultry industry due to mortality from infection and secondary infections. Methods of IBDV control include maintaining biosecurity as well as utilizing vaccination programs. Resistance to certain diseases may be passed from parent to offspring and can be utilized as a method of disease control. To establish if genetic resistance to IBDV exists in chickens, ARS scientists in Athens, Georgia, evaluated the susceptibility of ten inbred chicken lines to three strains of IBDV. The results showed differences in susceptibility to the classical IBDV strain STC and the very virulent IBDV strain rA, while no differences in susceptibility were observed upon challenge with the variant IBDV strain AL-2. The overall data suggest that genetic resistance to IBDV does exist depending upon the challenge strain of the virus and that further research into the mechanisms of the observed resistance may benefit future IBDV control strategies.

1. Stability of Newcastle disease virus (NDV). The thermal stability of Newcastle disease virus (NDV) vaccines significantly affects vaccine storage life and protective efficacy when exposed to environmental heat. To develop a thermal stable NDV vaccine as an in ovo vaccine vector, ARS researchers in Athens, Georgia, in collaboration with the scientists in the Institute of Animal Husbandry and Veterinary Sciences, Wuhan, China, investigated the mechanism for viral thermostability of an NDV vaccine. The results showed that the negative surface charge of the viral attachment glycoprotein was a critical determinant of viral thermal stability. It prevented the temperature-induced aggregation of glycoprotein and subsequent detachment from the virion surface. Then the virus could bind to and infect cells efficiently after heat treatment. Genetically engineered live and inactivated NDV vaccines with the increased negative surface charge of the attachment glycoprotein maintained their protective efficacy against the virulent NDV challenge after storage at 37 degree celsius for at least 10 and 60 days, respectively. Based on these data, we proposed a novel surface-charge-mediated mechanism for viral thermal stability, which could be used to design thermal stable enveloped virus vaccines rationally.

Review Publications
Mohanty, S.K., Donnelly, B., Temple, H., Bondoc, A., Mcneal, M., Tiao, G. 2021. T-bet deficiency attenuates bile duct injury in experimental biliary atresia. Cells. 10(12):3461.
Shang, Y., Li, L., Zhang, T., Luo, Q., Yu, Q., Zeng, Z., Li, L., Jia, M., Tang, G., Fan, S. 2022. Quantitative regulation of the thermal stability of enveloped virus vaccines by surface charge engineering to prevent the self-aggregation of attachment glycoproteins. PLoS Pathogens. 18(6). Article e1010564.