Divergent pathogenesis of two Chinese Crimean-Congo hemorrhagic fever viruses in cynomolgus macaques.

Abstract

Crimean-Congo hemorrhagic fever (CCHF), a highly pathogenic tick-borne disease in humans with mortality rates ranging from 5% to 82%. Although cynomolgus macaques have been used to model infection with strains such as Hoti and Afghanistan, the pathogenic characteristics of Chinese CCHFV isolates remain insufficiently defined. We evaluated the pathogenicity of two Chinese CCHFV strains in cynomolgus macaques: BA04032 (tick-derived) and 75024 (non-lethal human clinical isolate). Animal were monitored for clinical parameters, viremia, hematologic and biochemical changes, viral RNA loads in blood, swabs, and tissues, as well as histopathological alterations. Infection with strain 75024 resulted in mild disease manifestations, whereas infection with strain BA04032 produced more severe illness characterized primarily by fever, viremia, thrombocytopenia, leukopenia, and extensive viral replication in multiple organs. Although both viruses belong to the Asian lineage, phylogenetic analyses classify them into different genotypes, which may correlate with their distinct clinical and virological outcomes in this model. These findings demonstrate that Chinese isolates exhibit distinct clinical, virological, and pathological phenotypes in cynomolgus macaques, underscoring the value of this model for recapitulating aspects of CCHF disease, for pathogenesis research, and for evaluating medical countermeasures.