Location: Ruminant Diseases and Immunology Research
Project Number: 5030-32000-229-000-D
Project Type: In-House Appropriated
Start Date: Oct 1, 2021
End Date: Sep 30, 2026
Objective:
Objective 1: Determine the impact of variant and emerging viruses as causative agents of respiratory disease in ruminants, with special emphasis on the role of Bovine Viral Diarrhea virus (BVDV).
Subobjective 1A: Conduct whole genome phylogenetic analyses to support molecular epidemiological studies to characterize and determine the significance of ruminant respiratory viruses currently circulating in United States.
Subobjective 1B: Identify the molecular determinants that drive strain prevalence, emergence, evolution, virulence, and transmission of bovine respiratory viruses.
Subobjective 1C: Conduct metagenomic analyses of respiratory samples from feedlot cattle to determine presence and significance of bovine respiratory viruses.
Objective 2: Elucidate the host-pathogen interactions associated with the Bovine Respiratory Disease Complex.
Subobjective 2A: Identify host factors associated with viral infection that predispose to respiratory disease.
Subobjective 2B: Characterize cellular and humoral responses that drive protective immunity against viral respiratory pathogens.
Subobjective 2C: Characterize functional genomics of the host associated with susceptibility to respiratory disease.
Objective 3: Develop intervention strategies for controlling viral respiratory infections of ruminants.
Subobjective 3A: Develop vaccines and vaccination strategies that provide better cross-protection against emerging and antigenic variant field strains.
Subobjective 3B: Improve existing diagnostic tests and testing strategies for the early detection of respiratory viral pathogens of ruminants on relevant farm settings.
Subobjective 3C: Develop biotherapeutic platforms for feedlot cattle that induce rapid onset of immunity as a companion to respiratory disease vaccination.
Approach:
Bovine respiratory disease (BRD) is a major cause of production losses to the cattle industry. The aim of the research in this project plan is to provide scientific information to better understand the viral pathogenesis of BRD. In particular, the disease dynamics of host-pathogen interactions responsible for the BRD will be investigated. Agents of interest include bovine viral diarrhea virus (BVDV), bovine herpes virus-1 (BHV-1) and bovine respiratory syncytial virus (BRSV). This research will involve a multidisciplinary approach to address the broad and ambitious goal of controlling viral diseases of cattle, with a priority on respiratory viral pathogens. The approach used here is consistent with the multifactorial nature of bovine respiratory disease, as it results from an interplay of infection by multiple viral and bacterial pathogens, stress, immune dysfunction and environmental factors. The first objective of this project addresses the impact of variant and emerging viruses. Screening to determine the incidence of variant and emerging viruses will require the development of surveillance tools and methods to measure impact. This will lead to a greater understanding of viruses that play a role in BRD. A major question here is evaluation of currently marketed vaccines and whether it will be necessary to modify them to protect against emerging/variant viruses. There is a need to identify newly emerging/variant viruses that interact with the host in producing BRD. A second objective examines host/pathogen interactions, specifically to determine how respiratory viral pathogens interact with the host to moderate innate and adaptive immune responses. This includes interaction between BVDV, BRSV, BHV-1 and emerging/variant viruses. It is established that most BRD involves interactions of multiple agents, both viral and bacterial, thus experiments involving multiple agents will be conducted to examine this interplay and how each contributes to BRD. The third objective of this project plan involves defining events that promote the production of a strong, protective immune responses (both innate and acquired immunity). Results from this will reveal targets or points of intervention that can be utilized in the development of robust vaccines and management regimens that reduce the impact of BRD. The knowledge gained here will be used for the design of new vaccines, including subunit vaccines, or for providing greater knowledge for the selection of virus strains to be used in vaccines. This part of the project will evaluate the practical applications of information generated in the form of improved vaccines or vaccination strategies. The ultimate, cumulative goal of this research is to improve control of viral respiratory pathogens that will enhance cattle health and well-being, and reduce production costs for farmers and ranchers.
