Crimean-Congo hemorrhagic fever virus strains Hoti and Afghanistan cause viremia and mild clinical disease in cynomolgus monkeys

摘要

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus in the family Nairoviridae, and is the etiological agent of a severe and potentially fatal hemorrhagic fever disease in humans (CCHF). Despite being the most geographically widespread tick-borne arbovirus, CCHFV remains understudied, and the lack of specific pre- and post-exposure medical countermeasures for CCHFV infection has led to its inclusion in the World Health Organization (WHO) list of pathogens requiring urgent research attention. Development and approval of vaccines and therapeutics against CCHFV necessitates efficacy testing in animal models that accurately recapitulate human disease. Recently, a lethal model for CCHF in cynomolgus macaques utilizing the Hoti strain of CCHFV was reported. We sought to verify and expand on this model by inclusion of an additional CCHFV strain (Afghanistan), animals from different geographic origins, and assessing the impact of age. In contrast to the previous work, none of the animals in our study developed severe or lethal disease. Importantly, we were unable to attribute these contrasting findings with differences in experimental parameters, implying that the discrepancy between the findings in the previous study and ours is likely due to the outbred nature of the animals and the small number of animals used in BSL-4 studies.