Dynamic Changes in Host Immune Response During Crimean–Congo Hemorrhagic Fever and Severe Fever with Thrombocytopenia Syndrome in Mice

Crimean-Congo hemorrhagic fever virus (CCHFV) and severe fever with thrombocytopenia syndrome virus (SFTSV) are tick-borne pathogens that cause severe illness and high mortality. Early diagnosis is critical, particularly in resource-limited settings, to enable timely intervention. Host gene expression profiling offers a promising approach to identify potential biomarkers for early detection, disease staging, and logical treatment decision-making. Using a transient IFN-α/β receptor-suppressed mouse model, we performed targeted transcriptomic analysis on blood samples collected at 2, 3, and 4 days after CCHFV or SFTSV challenge. A significant increase in viral load and changes in gene expression were observed as early as two days post-challenge. CCHFV induced a progressively evolving interferon-driven response, while SFTSV triggered rapid, sustained immune activation. Affected targets included interferon-stimulated genes, chemokines, cytokines, Toll-like receptors, and genes associated with viral evasion and innate immune response. Despite shared expression patterns, unique genes were identified as potential biomarkers to distinguish between CCHFV and SFTSV infections. Differential gene expression revealed distinct immune response dynamics, with suppression of critical immune regulatory genes suggesting transcriptional signatures associated with viral evasion mechanisms contributing to disease severity. These findings provide a comparative analysis of molecular pathways and gene expression changes, offering critical insights for biomarker discovery, effective triage, and evaluation of appropriate medical intervention.