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Divergent Pathogenesis of 2 Chinese Crimean-Congo Hemorrhagic Fever Viruses in Cynomolgus Macaques
Juhong Rao1,2, Yanfeng Yao3, Xue Hu1
1State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
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.
Insights
Chinese Crimean-Congo hemorrhagic fever virus (CCHFV) isolates show varied pathogenicity in cynomolgus macaques. One strain caused severe illness, while another resulted in mild disease, highlighting differences in CCHF pathogenesis.
Area of Science:
- Virology
- Pathogen Research
- Animal Models
Background:
- Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne illness with high mortality.
- Chinese CCHFV isolates' pathogenicity is not well-understood.
- Cynomolgus macaques are a relevant model for CCHF research.
Purpose of the Study:
- To assess the pathogenicity of two Chinese CCHFV strains in cynomolgus macaques.
- To compare the clinical and virological outcomes of different CCHFV isolates.
- To evaluate the utility of cynomolgus macaques for studying CCHF.
Main Methods:
- Two Chinese CCHFV strains (BA04032 and 75024) were used to infect cynomolgus macaques.
- Animals were monitored for clinical signs, viremia, and hematological changes.
- Viral RNA loads and histopathological alterations were analyzed in various samples.
Main Results:
- Strain 75024 caused mild disease, while strain BA04032 induced severe illness with fever, viremia, and organ involvement.
- Significant differences in viral replication and clinical manifestations were observed between the strains.
- Phylogenetic analysis indicated distinct genotypes for the two Chinese CCHFV isolates.
Conclusions:
- Chinese CCHFV isolates exhibit distinct pathogenic phenotypes in cynomolgus macaques.
- The cynomolgus macaque model effectively recapitulates CCHF disease aspects.
- This study aids CCHF pathogenesis research and medical countermeasure evaluation.
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