Location: Zoonotic and Emerging Disease Research
Project Number: 3022-32000-027-036-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Sep 15, 2025
End Date: Sep 14, 2026
Objective:
This integrated research program supports U.S. agricultural biosecurity and national defense by addressing three critical and interrelated objectives: the isolation and characterization of zoonotic viruses with potential agricultural impact, the investigation of host responses to high-consequence pathogens such as henipaviruses, and the evaluation of immune responses to emerging threats. By identifying and characterizing viral agents through genomic, molecular, and in vivo analyses, the program generates foundational data necessary for risk assessment, diagnostic development, and preparedness planning. Through in vitro and archival studies, the project elucidates mechanisms of cross-species transmission and immune modulation, helping to identify molecular targets for therapeutic and vaccine development. Finally, by assessing neutralizing antibody responses in livestock and wildlife populations, the program enhances our understanding of population-level exposure and immunity. Collectively, these efforts strengthen the United States’ ability to detect, respond to, and mitigate zoonotic spillover events, protect food security, and sustain agricultural resilience in the face of evolving biological threats.
Approach:
Objective 1: Isolation and Characterization of Zoonotic Viruses Relevant to U.S. Agriculture
The first objective aims to identify and characterize viral agents with the potential to threaten U.S. agricultural systems. As part of this effort, biological samples collected from USDA collaborative surveillance and research sites will be transferred to the University of Texas Medical Branch (UTMB) for detailed virological analysis. Characterization of these agents will involve multiple approaches, including viral isolation in culture, in vitro studies to determine host cell susceptibility, and in vivo studies to assess host range and virulence. Molecular investigations such as full-genome sequencing and host transcriptomic profiling will further clarify viral diversity and mechanisms of host interaction. These data are essential for risk assessments, countermeasure development, and preparedness planning, especially for novel or understudied pathogens with zoonotic potential.
Objective 2: Investigation of Host Responses to Henipaviruses Using In Vitro Systems and Archival In Vivo Samples
Henipaviruses represent a critical family of emerging zoonotic pathogens with demonstrated capacity to infect both livestock and humans, often with high mortality. This objective focuses on dissecting the molecular interactions between henipaviruses and host cells to better understand mechanisms of pathogenesis, immune evasion, and cross-species transmission. Using a combination of established cell lines, primary cells, and organoid/organ-chip models, experimental infections will be conducted to measure host and viral gene expression responses through transcriptomic analysis. To identify key mediators of infection or immune modulation, specific host pathways will be targeted using RNA interference or other knockdown strategies. Complementary analysis will be performed using archival in vivo samples from prior henipavirus studies, enabling histological and molecular characterization of host responses in tissue contexts. These insights will support the development of diagnostic markers and therapeutic strategies and inform future modeling of disease spread and intervention impact.
Objective 3: Evaluation of Immune Responses to Agricultural Zoonotic Threats
Understanding the immune response to agricultural zoonotic pathogens is essential for guiding vaccine development, serological surveillance, and post-exposure interventions. This objective seeks to evaluate the presence and potency of virus-neutralizing antibodies in samples collected from USDA partner sites, focusing on pathogens that require maximum biocontainment (BSL-4) due to their high consequence for animal and human health. Live-virus neutralization assays will be conducted at UTMB using standardized protocols and available virus isolates. Priority will be given to viruses known or suspected to affect livestock productivity or food safety. These studies will provide a clearer understanding of population-level exposure, immune protection, and vulnerability, contributing directly to agricultural biosecurity and zoonotic disease preparedness efforts.