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Research Project: Ecology of Crimean-Congo Hemorrhagic Fever Virus

Location: Foreign Arthropod Borne Animal Disease Research

Project Number: 3022-32000-062-006-S
Project Type: Non-Assistance Cooperative Agreement

Start Date: Aug 1, 2019
End Date: Jul 31, 2024

Crimean-Congo hemorrhagic fever (CCHF) is caused by a tick-borne virus, in the family Nairoviridae. Major gaps remain regarding disease ecology and life cycle in livestock species and ticks. This project will specifically address research gaps in the BSL4 research program at the National Agro and Bio-Defense Facility (NBAF), Manhattan, KS. Additional benefits include enhanced knowledge of ticks and tick-borne pathogens. Collected tick specimens will be shared and shipped to our partner laboratory at the Centers for Disease Control and Prevention Viral Special Pathogens Branch, Atlanta Georgia, for further virus isolation and molecular characterization. These specimens will form a key biological resource of recent fieldstrains and increase our understanding of the ecology of CCHFV from regions previously underrepresented, increase our capacity to carry out ecological studies on zoonotic diseases in endemic settings, and establish biosafety and biosecurity protocols for sample collection, transport and laboratory analysis. Field-strain collections will form the basis of a relevant and highly valuable bio-bank for USDA NBAF once operational. Where feasible, the post-doctoral fellow will participate in BSL-4 training and laboratory analyses to ensure USDA NBAF has experienced field ecology personnel ready to investigate tickborne zoonotic viruses under field and maximum laboratory containment settings. Specific Objectives: 1- Initiate field studies on the ecology of Crimean-Congo hemorrhagic fever virus in endemic settings, including ticks, domesticated livestock and wildlife. 2- Train future NBAF personnel on field studies for BSL4 program. 3- Establish a robust CCHFV genomics and bioinformatics approach to understand the molecular determinants of pathogenesis and inform the development advanced diagnostics and countermeasures.

The University of California, Davis One Health Institute (UCD OHI) will leverage on-going activities in Tanzania and Sierra Leone to investigate Crimean-Congo hemorrhagic fever virus ecology among ticks and domesticated livestock and wildlife. Theses on-going collaborations have led to the discovery of multiple novel and known high-consequence viral hemorrhagic fever viruses. Samples will thrn be shipped from Tanzania and Sierra Leone to CDC for further analysis and testing. In conjunction with the Centers for Disease Control and Prevention Viral Special Pathogens Branch (CDC), we will work to genetically characterize CCHF viral isolates and nucleic acid specimens collected in Sierra Leone and Tanzania. Attempts will be made to isolate CCHFV from field collected specimens to build a bio-bank of CCHF viruses for later analyses at NBAF and to accelerate the development of tools such as CCHFV reverse genetics systems. Bioinformatic and phylogeographic analyses will be conducted to identify potentially virulence determining mutations across recent field isolates to later screen in a well-established animal model. Using a combined bioinformatic, molecular virology, and in vivo platform approach we will attempt to identify viral mutations which influence CCHFV virulence across genetically divergent virus isolates.