Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Nat Microbiol. 2018 May;3(5):556-562. doi: 10.1038/s41564-018-0141-7. Epub 2018 Apr 9.
Crimean-Congo haemorrhagic fever (CCHF) is the most medically significant tick-borne disease, being widespread in the Middle East, Asia, Africa and parts of Europe . Increasing case numbers, westerly movement and broadly ranging case fatality rates substantiate the concern of CCHF as a public health threat. Ixodid ticks of the genus Hyalomma are the vector for CCHF virus (CCHFV), an arbovirus in the genus Orthonairovirus of the family Nairoviridae. CCHFV naturally infects numerous wild and domestic animals via tick bite without causing obvious disease. Severe disease occurs only in humans and transmission usually happens through tick bite or contact with infected animals or humans. The only CCHF disease model is a subset of immunocompromised mice. Here, we show that following CCHFV infection, cynomolgus macaques exhibited hallmark signs of human CCHF with remarkably similar viral dissemination, organ pathology and disease progression. Histopathology showed infection of hepatocytes, endothelial cells and monocytes and fatal outcome seemed associated with endothelial dysfunction manifesting in a clinical shock syndrome with coagulopathy. This non-human primate model will be an invaluable asset for CCHFV countermeasures development.
克里米亚-刚果出血热(CCHF)是最重要的虫媒传染病之一,广泛分布于中东、亚洲、非洲和欧洲部分地区。不断增加的病例数量、向西移动以及广泛的病死率证实了 CCHF 作为公共卫生威胁的存在。属软蜱的钝缘蜱是 CCHF 病毒(CCHFV)的传播媒介,该病毒属于纳罗病毒科的正粘病毒属。CCHFV 通过蜱叮咬自然感染许多野生动物和家畜,但不会引起明显的疾病。严重疾病仅发生在人类中,传播通常通过蜱叮咬或接触感染的动物或人类发生。唯一的 CCHF 疾病模型是一组免疫功能低下的小鼠。在这里,我们表明,感染 CCHFV 后,食蟹猴表现出与人类 CCHF 相似的标志性特征,包括病毒传播、器官病理学和疾病进展。组织病理学显示感染了肝细胞、内皮细胞和单核细胞,致命结果似乎与内皮功能障碍有关,表现为伴有凝血功能障碍的临床休克综合征。这种非人类灵长类动物模型将成为 CCHFV 对策开发的宝贵资源。