An Early Passage Human Isolate of Kyasanur Forest Disease Virus Shows Acute Neuropathology in Experimentally Infected CD-1 Mice
An Early Passage Human Isolate of Kyasanur Forest Disease Virus Shows Acute Neuropathology in Experimentally Infected CD-1 Mice
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DOI：
10.1089/vbz.2015.1917
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发表时间：
2016-07-01
影响因子：
2.1
通讯作者：
Mourya, Devendra T.
中科院分区：
文献类型：
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作者：
Basu, Atanu;Yadav, Pragya;Mourya, Devendra T.
背景：Kyasanur 森林病病毒 (KFDV) 是一种蜱传黄病毒，可导致人类严重疾病。疾病谱多种多样，从亚临床感染到伴有出血并发症的致命病例。 KFDV 的病理学仍不完全清楚。方法：本研究描述了用早期传代人 KFDV 分离株实验感染的婴儿 CD-1 小鼠的组织病理学和免疫组织化学结果。结果：急性组织学变化主要见于大脑。变化范围包括神经胶质增生、炎症反应、坏死、神经损失以及中后脑结构中的合胞体形成。肝脏中观察到的镜下病变主要是肝细胞坏死和空泡形成，小肠中观察到明显的上皮细胞坏死。 KFDV 抗原可以在同一器官中通过敏感的免疫组织化学标记进行染色。结论：本研究的结果表明神经病理学是早期传代的人类 KFDV 分离株的主要表现。重要的是，这表明 KFDV 可能主要引起神经系统疾病，继发性器官损伤可能是由于疾病病理本身造成的。使用初级低传代人类分离株和神经病理学特征也可能更适合开发用于测试潜在抗病毒药物和治疗药物的挑战模型。
Background: Kyasanur Forest disease virus (KFDV) is a tick-borne Flavivirus that causes a severe illness in humans. Disease spectrum can vary from subclinical infection to fatal cases with hemorrhagic complications. The pathology of KFDV remains incompletely understood.Methods: This study describes the histopathologic and immunohistochemical findings in experimentally infected infant CD-1 mice with an early passage human KFDV isolate.Results: Acute histological changes were primarily seen in the brain. The spectrum of changes included gliosis, inflammatory response, necrosis, neural loss, and syncytium formation in mid and hind brain structures. Microscopic lesions observed in the liver were mainly necrosis and vacuolation of hepatocytes and in small intestine, prominent epithelial cell necrosis. KFDV antigens could be stained by a sensitive immunohistochemical labeling in the same organs.Conclusions: Findings from this study are suggestive of neuropathology as the main manifestation of an early passaged human KFDV isolate. Importantly, this suggests that KFDV may be causing primarily a neurologic disease and secondary organ damage could be because of disease pathology per se. The use of primary low passage human isolates and neuropathology profile could also be more apt in developing a challenge model for testing potential antivirals and therapeutic agents.