Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus
Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus
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DOI：
10.1177/0300985816677153
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发表时间：
2017-05-01
影响因子：
2.4
通讯作者：
Cashman, K. A.
中科院分区：
文献类型：
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作者：
Bell, T. M.;Shaia, C. I.;Cashman, K. A.
拉萨病毒感染导致一种急性、多系统的病毒性出血热，每年在西非估计有100000至300000人感染。这项发病机制研究评估了雾化和皮下接种LASV Josiah株后豚鼠疾病的时间进展，以及13株豚鼠作为拉沙热动物模型的有效性。实验感染后，对豚鼠(n=67)进行连续取样，以评估感染的时间进程、大体和组织学损害以及血清化学和血液学变化。豚鼠在暴露后第5~6天出现病毒血症，第7~8天出现临床体征。完整的血细胞计数显示淋巴细胞减少和血小板减少。大体病理发现包括皮肤损害和充血的肺部。组织学损害包括6-7天的皮质淋巴组织耗竭和7-8天的淋巴组织细胞间质性肺炎。肝组织中也有散在的肝细胞变性和细胞死亡，其他组织包括毛发皮肤、肺、心脏、肾上腺、淋巴结、胸腺和脾，程度较轻。PE后第5~6天，淋巴结内的成纤维细胞、网状细胞和巨噬细胞/树突状细胞是最早发现病毒抗原的细胞。这项研究证明了人类感染拉萨病毒病与实验性豚鼠感染之间的相似之处。这些共同的病理特征支持了根据食品和药物管理局的动物规则，豚鼠作为疫苗和治疗开发的额外动物模型的用途。
Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100000 to 300000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs (Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes. Guinea pigs developed viremia on day 5 to 6 postexposure (PE), with clinical signs appearing by day 7 to 8 PE. Complete blood counts revealed lymphopenia and thrombocytopenia. Gross pathologic findings included skin lesions and congested lungs. Histologic lesions consisted of cortical lymphoid depletion by day 6 to 7 PE with lymphohistiocytic interstitial pneumonia at 7 to 8 days PE. Scattered hepatocellular degeneration and cell death were also noted in the liver and, to a lesser extent, in other tissues including the haired skin, lung, heart, adrenal gland, lymph nodes, thymus, and spleen. The first cell types to demonstrate staining for viral antigen were fibroblastic reticular cells and macrophages/dendritic cells in the lymph nodes on day 5 to 6 PE. This study demonstrates similarities between Lassa viral disease in human infections and experimental guinea pig infection. These shared pathologic characteristics support the utility of guinea pigs as an additional animal model for vaccine and therapeutic development under the Food and Drug Administration's Animal Rule.