Wild-type Puumala hantavirus infection induces cytokines, C-reactive protein, creatinine, and nitric oxide in cynomolgus macaques
Wild-type Puumala hantavirus infection induces cytokines, C-reactive protein, creatinine, and nitric oxide in cynomolgus macaques
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DOI：
10.1128/jvi.76.1.444-449.2002
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发表时间：
2002-01-01
影响因子：
5.4
通讯作者：
Lundkvist, Å
中科院分区：
文献类型：
--
作者：
Klingström, J;Plyusnin, A;Lundkvist, Å
汉坦病毒引起两种严重的人类疾病：肾综合征出血热（HFRS）和汉坦病毒肺综合征（HPS）。每年报告的病例约为200 000例，迄今为止没有具体的治疗方法。研究HFRS和HPS医学方面的一个主要障碍是缺乏适当的动物模型。在这里，我们表明，野生型普马拉汉坦病毒感染食蟹猴导致HFRS的典型体征，包括嗜睡，厌食，蛋白尿，和/或血尿，除了细胞因子（白细胞介素6 [IL-6]，IL-10，和肿瘤坏死因子α），C-反应蛋白，肌酐，和一氧化氮反应。从接种后第3 - 7天至接种后第24 - 28天，在血浆中检测到病毒RNA，回收了感染性病毒，病毒特异性免疫应答（免疫球蛋白M [IgM]、IgG和中和抗体）与在人体中观察到的相似。本研究结果为汉坦病毒病的发病机制、候选疫苗和抗病毒药物的研究提供了一个有价值的工具。
Hantaviruses cause two severe human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Approximately 200,000 cases are reported annually, and there is to date no specific treatment available. A major obstacle in studying the medical aspects of HFRS and HPS has been the lack of an adequate animal model. Here we show that infection of cynomolgus macaques by wild-type Puumala hantavirus resulted in typical signs of HFRS including lethargy, anorexia, proteinuria, and/or hematuria, in addition to cytokine (interleukin 6 [IL-6], IL-10, and tumor necrosis factor alpha), C-reactive protein, creatinine, and nitric oxide responses. Viral RNA was detected in plasma from days 3 to 7 postinoculation until days 24 to 28 postinoculation, infectious virus was recovered, and the virus-specific immune responses (immunoglobulin M [IgM], IgG, and neutralizing antibodies) mimicked those seen in humans. The results indicated that the monkey model will provide a valuable tool for studies of pathogenesis, candidate vaccines, and antivirals for hantavirus disease.