Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis
Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis
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DOI：
10.3390/v11010067
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发表时间：
2019-01-01
期刊：
影响因子：
4.7
通讯作者：
Johnson, Reed F.
中科院分区：
文献类型：
--
作者：
Cornish, Joseph P.;Moore, Ian N.;Johnson, Reed F.
猴出血热病毒（SHFV）在猕猴（猕猴科：猕猴科）中引起暴发性和通常致命的病毒性出血热（VHF），但在斑猴（斑猴科：赤猴）中引起亚临床感染。这种病程上的差异提供了一个独特的机会，可以比较宿主在生物学上相似的易感和难治性动物中对引起甚高频病毒感染的反应。旱猴和恒河猴同时接种SHFV疫苗。与在恒河猴中观察到的严重疾病不同，patas猴发展为一种有限的临床疾病，其特征是全血细胞计数、血清化学变化和淋巴结病的发展。暴露后2天循环血液中可测到病毒RNA，其持续时间因物种而异。在斑猴和恒河猴的末端组织中均检测到传染性病毒。在斑猴和恒河猴之间观察到血清干扰素(IFN)-、单核细胞趋化蛋白(MCP)-1和白细胞介素(IL)-6浓度变化的不同程度重叠，表明存在共同的和物种特异性的细胞因子对感染的反应。同样，对终末期猴子肝脏的定量免疫组织化学和全血流式细胞术显示，巨噬细胞、自然杀伤细胞和t细胞的变化有不同程度的重叠。宿主反应中意想不到的重叠程度表明，宿主对感染的反应中相对较小的亚群可能是驱动出血热发病机制的原因。此外，在patas和恒河猴中比较SHFV感染提供了一个实验模型来表征与病毒性出血热相关的宿主反应机制，并评估泛病毒性出血热对策。
Simian hemorrhagic fever virus (SHFV) causes a fulminant and typically lethal viral hemorrhagic fever (VHF) in macaques (Cercopithecinae: Macaca spp.) but causes subclinical infections in patas monkeys (Cercopithecinae: Erythrocebus patas). This difference in disease course offers a unique opportunity to compare host responses to infection by a VHF-causing virus in biologically similar susceptible and refractory animals. Patas and rhesus monkeys were inoculated side-by-side with SHFV. Unlike the severe disease observed in rhesus monkeys, patas monkeys developed a limited clinical disease characterized by changes in complete blood counts, serum chemistries, and development of lymphadenopathy. Viral RNA was measurable in circulating blood 2 days after exposure, and its duration varied by species. Infectious virus was detected in terminal tissues of both patas and rhesus monkeys. Varying degrees of overlap in changes in serum concentrations of interferon (IFN)-, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6 were observed between patas and rhesus monkeys, suggesting the presence of common and species-specific cytokine responses to infection. Similarly, quantitative immunohistochemistry of livers from terminal monkeys and whole blood flow cytometry revealed varying degrees of overlap in changes in macrophages, natural killer cells, and T-cells. The unexpected degree of overlap in host response suggests that relatively small subsets of a host's response to infection may be responsible for driving hemorrhagic fever pathogenesis. Furthermore, comparative SHFV infection in patas and rhesus monkeys offers an experimental model to characterize host-response mechanisms associated with viral hemorrhagic fever and evaluate pan-viral hemorrhagic fever countermeasures.