Simoes E A, Hayward A R, Ponnuraj E M, Straumanis J P, Stenmark K R, Wilson H L, Babu P G
Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Pediatr Dev Pathol. 1999 Jul-Aug;2(4):316-26. doi: 10.1007/s100249900129.
The Bonnet monkey model of respiratory syncytial virus (RSV) infection may be a useful nonhuman primate model for studying RSV disease in humans because Bonnet monkeys can predictably be infected to obtain an orderly sequence of morphologic, cytologic, virologic, serologic, and inflammatory changes related to time of infection. Young feral Bonnet monkeys, Macaca radiata, were infected endotracheally with 10(6) plaque-forming units (pfu) of the Long strain of RSV. RSV was recovered from the animals' lungs at necropsy on days 3, 5, and 7 with the highest viral titer obtained on day 3 (1.1 and 5.2 x 10(3) pfu/g of tissue in the upper and lower lobes, respectively). RSV antigen and F protein mRNA were detected 3-5 days after infection in alveolar macrophages and in the epithelium of bronchi, terminal bronchioles, and alveoli. Histologic analysis of RSV-infected lungs at necropsy revealed progressive bronchiolar mucosal and submucosal inflammation, periarterial mononuclear interstitial inflammation, and focal alveolitis, with a maximal response at 7 days after infection. Cell counts in bronchoalveolar lavage (BAL) increased with time with neutrophils and macrophages predominating on day 3 (6.47 and 5.85 x 10(5)/mm3, respectively) and lymphocytes predominating on day 9 (4.18 x 10(5)/mm3). Serum-neutralizing antibody appeared on day 5 and IgG antibody to RSV was detected on day 9. This sequence of morphologic, cytologic, virologic, serologic, and inflammatory change following RSV infection creates a useful model in the study of experimentally induced RSV disease with a potential for testing future vaccine-induced alterations in RSV disease response.
呼吸道合胞病毒（RSV）感染的帽猴模型可能是一种用于研究人类RSV疾病的有用的非人类灵长类动物模型，因为帽猴可以被可预测地感染，以获得与感染时间相关的形态学、细胞学、病毒学、血清学和炎症变化的有序序列。幼年野生帽猴（恒河猴）经气管内接种10^6个RSV长株的空斑形成单位（pfu）。在尸检时于第3、5和7天从动物肺部回收RSV，第3天获得最高病毒滴度（上叶和下叶组织中分别为1.1和5.2×10^3 pfu/g）。感染后3 - 5天在肺泡巨噬细胞以及支气管、终末细支气管和肺泡的上皮细胞中检测到RSV抗原和F蛋白mRNA。尸检时对RSV感染的肺部进行组织学分析显示，细支气管黏膜和黏膜下炎症、动脉周围单核细胞间质炎症以及局灶性肺泡炎呈进行性发展，感染后7天反应最为强烈。支气管肺泡灌洗（BAL）中的细胞计数随时间增加，第3天以中性粒细胞和巨噬细胞为主（分别为6.47和5.85×10^5/mm³），第9天以淋巴细胞为主（4.18×10^5/mm³）。血清中和抗体在第5天出现，第9天检测到针对RSV的IgG抗体。RSV感染后这种形态学、细胞学、病毒学、血清学和炎症变化的序列为研究实验性诱导的RSV疾病创造了一个有用的模型，具有测试未来疫苗诱导的RSV疾病反应改变的潜力。
