Experimental yellow fever virus infection in the squirrel monkey (Saimiri spp.) I: gross anatomical and histopathological findings in organs at necropsy

BACKGROUND Non-human primates contribute to the spread of the yellow fever virus (YFV) and the establishment of transmission cycles in endemic areas. OBJECTIVE To describe the severe histopathological aspects of YFV infection, 10 squirrel monkeys were infected with YFV and blood, brain, liver, kidney, spleen, heart, lung, lymph node and stomach were collected at 1-7, 10, 20 and 30 days post-infection (dpi). METHODS Histopathological analysis and detection of the genome and viral antigens and neutralising antibodies were performed by RT-PCR, immunohistochemistry and neutralisation test, respectively. FINDINGS Only one animal died from the experimental infection. The genome and viral antigens were detected in all investigated organs (1-30 dpi) and the neutralising antibodies from seven to 30 dpi. The brain contained perivascular haemorrhage (6 dpi); in the liver, midzonal haemorrhage and lytic necrosis (6 dpi) were observed. The kidney had bleeding in the Bowman’s capsule and tubular necrosis (6 dpi). Pyknotic lymphocytes were observed in the spleen (1-20 dpi), the lung had haemorrhage (2-6 dpi), in the endocardium it contained nuclear pyknosis and necrosis (2-3 dpi) and the stomach contained blood in the lumen (6 dpi). MAIN FINDINGS Squirrel monkeys reliably reproduced the responses observed in human cases of yellow fever and, therefore, constitute an excellent experimental model for studies on the pathophysiology of the disease.背景：非人灵长类动物可推动黄热病毒（Yellow Fever Virus, YFV）的传播，并助力流行区域内黄热病毒传播循环的建立。 研究目的：为阐明黄热病毒感染的严重组织病理学特征，本研究将10只松鼠猴感染黄热病毒，并于感染后1~7天、10天、20天及30天（days post-infection, dpi）采集血液、脑、肝、肾、脾、心脏、肺、淋巴结及胃组织样本。 方法：分别通过逆转录聚合酶链反应（RT-PCR）、免疫组织化学法及中和试验，开展组织病理学分析、病毒基因组与病毒抗原检测及中和抗体检测。 结果：仅1只实验感染动物死亡。在所有检测的组织样本中（感染后1~30天）均检出病毒基因组与病毒抗原，且在感染后7~30天可检测到中和抗体。感染后6天，脑组织可见血管周围出血；肝脏可见中区出血与溶解性坏死；肾脏可见鲍曼囊出血及肾小管坏死。感染后1~20天，脾脏可见固缩淋巴细胞；感染后2~6天，肺部出现出血；感染后2~3天，心内膜可见核固缩与坏死；感染后6天，胃部管腔可见血液。 主要结论：松鼠猴可稳定复现人类黄热病病例的病理反应，因此是研究黄热病病理生理学的优秀实验动物模型。