Klingström J, Plyusnin A, Vaheri A, Lundkvist A
Swedish Institute for Infectious Disease Control, S-171 82 Stockholm, Sweden.
J Virol. 2002 Jan;76(1):444-9. doi: 10.1128/jvi.76.1.444-449.2002.
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.
肾综合征出血热（HFRS）和汉坦病毒肺综合征（HPS）。每年报告的病例约有20万例，迄今为止尚无特效治疗方法。研究HFRS和HPS医学方面的一个主要障碍是缺乏合适的动物模型。在此我们表明，野生型普马拉汉坦病毒感染食蟹猕猴会导致HFRS的典型症状，包括嗜睡、厌食、蛋白尿和/或血尿，此外还会引发细胞因子（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。接种后第3天至第7天直至接种后第24天至第28天，在血浆中检测到病毒RNA，分离出了传染性病毒，并且病毒特异性免疫反应（免疫球蛋白M [IgM]、IgG和中和抗体）与人类相似。结果表明，该猴模型将为汉坦病毒病的发病机制、候选疫苗和抗病毒药物研究提供有价值的工具。
