Divergent Pathogenesis of 2 Chinese Crimean–Congo Hemorrhagic Fever Viruses in Cynomolgus Macaques

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a highly pathogenic tick-borne disease with mortality rates of 5% to 82%. Although cynomolgus macaques models exist for Hoti and Afghanistan strains, Chinese CCHFV isolates remain insufficiently defined. METHODS: We evaluated the pathogenicity of 2 Chinese CCHFV strains in cynomolgus macaques: BA04032 (tick-derived) and 75024 (non-lethal human clinical isolate). Animals were monitored for clinical parameters, viremia, hematologic and biochemical changes, viral RNA loads in blood, swabs, and tissues, and histopathological alterations. RESULTS: Infection with strain 75024 caused mild disease, whereas BA04032 produced more severe illness with fever, viremia, thrombocytopenia, leukopenia, and extensive viral replication in multiple organs. Despite belonging to the Asian lineage, the two viruses fall into different genotypes with distinct clinical outcomes in this model. CONCLUSIONS: Chinese isolates exhibit distinct disease phenotypes in cynomolgus macaques, underscoring the value of this model for pathogenesis studies and evaluation of medical countermeasures.