Characterization of a lethal Crimean-Congo hemorrhagic fever virus infection model in interferon-deficient mice for studies of virus pathogenicity and vaccine efficacy

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus causing severe human disease and representing a significant public health threat. The absence of licensed vaccines and specific antiviral therapies highlights the need for well-characterized experimental models suitable for studying viral pathogenicity and evaluating medical countermeasures. In this study, we established and characterized an integrated in vitro and in vivo platform for CCHFV research. Virus propagation was optimized by comparing Vero E6 and SW-13 cell lines. SW-13 cells supported efficient CCHFV replication resulting in pronounced virus-induced cytopathic effects, whereas no detectable cytopathic effects were observed in Vero E6 cells. Virus titers determined by cytopathic effect based endpoint dilution and antigen ELISA coincided, supporting the use of SW-13 cells for virus stock preparation. Using virus stocks generated in SW-13 cells, interferon-deficient mice were infected with different doses of CCHFV to assess dose-dependent pathogenicity. Infection resulted in severe disease and high mortality across all tested doses. Based on survival analysis, a dose of 10 TCID50 was selected for further characterization, which revealed progressive weight loss and high viral loads in peripheral organs. Overall, this study establishes a robust IFN knockout mouse model suitable for studying CCHFV pathogenicity, comparing viral genovariants, and evaluating vaccines, antiviral compounds, and neutralizing antibodies.