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by claude@2026-07, 2026-07-30
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IFNAR−/− mice infected with CCHFV strains Afghanistan09 and Kosovo Hoti exhibited significant weight loss and viral dissemination, with the Afghanistan09 strain causing more severe disease, validating these models for evaluating medical countermeasures.
Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a severe hemorrhagic fever in humans, associated with case fatality rates ranging from 10 to 40%. Due to the lack of approved vaccines or specific antiviral treatments, CCHFV is classified as a biosafety level 4 (BSL4) pathogen in most countries and designated a priority pathogen by the World Health Organization (WHO). To facilitate the preclinical assessment of medical countermeasures, we have established two murine models using C57BL/6J IFNAR −/− mice, which lack the IFNα/β receptor, infected with the phylogenetically distinct CCHFV strains Afghanistan09-2990 (Afg09) and Kosovo Hoti (Hoti). Infection with both CCHFV strains in IFNAR −/− mice resulted in significant weight loss, with Afg09 infection leading to more severe clinical disease. Quantitative analysis of viral RNA revealed widespread viral dissemination across multiple organs in both models. Detection of infectious virus varied by organ and strain. These results confirm and extend previous findings, providing a deeper understanding of CCHFV strain-specific pathogenesis in IFNAR −/− mice. Thereby, these mouse models represent valuable tools for the evaluation of antiviral therapeutics and vaccine candidates, enabling the investigation of cross-lineage protection against genetically diverse CCHFV isolates.
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Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a severe hemorrhagic fever in humans, associated with case fatality rates ranging from 10 to 40%. Due to the lack of approved vaccines or specific antiviral treatments, CCHFV is classified as a biosafety level 4 (BSL4) pathogen in most countries and designated a priority pathogen by the World Health Organization (WHO). To facilitate the preclinical assessment of medical countermeasures, we have established two murine models using C57BL/6J IFNAR−/− mice, which lack the IFNα/β receptor, infected with the phylogenetically distinct CCHFV strains Afghanistan09-2990 (Afg09) and Kosovo Hoti (Hoti). Infection with both CCHFV strains in IFNAR−/− mice resulted in significant weight loss, with Afg09 infection leading to more severe clinical disease. Quantitative analysis of viral RNA revealed widespread viral dissemination across multiple organs in both models. Detection of infectious virus varied by organ and strain. These results confirm and extend previous findings, providing a deeper understanding of CCHFV strain-specific pathogenesis in IFNAR−/− mice. Thereby, these mouse models represent valuable tools for the evaluation of antiviral therapeutics and vaccine candidates, enabling the investigation of cross-lineage protection against genetically diverse CCHFV isolates.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵# Marcel Benz1, Martina Huxol1, Lennart Kämper1, Michael Klüver1,2, Lars Meier1,2, Pauline Neubecker1,2,
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