A LAMB MODEL FOR HUMAN RESPIRATORY SYNCYTIAL VIRUS-INFECTION
A LAMB MODEL FOR HUMAN RESPIRATORY SYNCYTIAL VIRUS-INFECTION
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DOI：
10.1002/ppul.1950150305
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发表时间：
1993-03-01
影响因子：
3.1
通讯作者：
PIEDRA, PT
中科院分区：
文献类型：
--
作者：
LAPIN, CD;HIATT, PW;PIEDRA, PT
呼吸道合胞病毒（RSV）是小儿毛细支气管炎和肺炎的最重要原因。RSV疾病动物模型的开发有助于更好地理解婴儿和儿童中RSV感染引起的气道疾病的病理生理学。每组6只羔羊经气管内（IT）或鼻内（IN）接种RSV人株（H-RSV）。对于对照组，8只羔羊接受IT无病毒细胞裂解物。与IN接种H-RSV或IT安慰剂相比，IT后观察到呼吸急促和发热的频率显著更高（呼吸急促：分别为69天中的20天、63天中的5天和89天中的3天，P < 0.001;发热：分别为69天中的6天、63天中的0天和89天中的1天，P < 0.02）。IT组（69天中的14天）和IN组（63天中的15天）的鼻液产生频率明显高于安慰剂组（87天中的2天，P <0.001）。免疫后1周，IT H-RSV组RSV特异性中和抗体几何平均滴度（GMT，对数2的算术转换）显著高于安慰剂组（72 vs. 6.7，P < 0.03）。接种后第二周，两组H-RSV感染组的RSV特异性中和抗体滴度水平相当，第二至第四周的GMT显著高于安慰剂组（分别为144、128和4.8，P < 0.0008）。三组间上呼吸道的细菌分离株相当。接种后第28天，三个研究组的组织学无明显变化。H-RSV感染羔羊后出现明显的临床症状，提示H-RSV感染羔羊模型可用于描述H-RSV感染肺损伤的发病机制。
Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis and pneumonia in young children. The development of an animal model of RSV disease serves to better understanding the pathophysiology of airway disease from RSV infection in infants and children. Groups of six lambs were inoculated intratracheally (IT) or intranasally (IN) with a human strain of RSV (H-RSV). For controls 8 lambs received IT virus-free cell lysate. Tachypnea and fever were observed significantly more often following IT than following IN inoculation of H-RSV or IT placebo (for tachypnea: 20 of 69 days, 5 of 63 days, and 3 of 89 days, respectively, P < 0.001; for fever: 6 of 69 days, 0 of 63 days, and 1 of 89 days, respectively, P < 0.02). Nasal fluid production was significantly more frequent in both IT (14 of 69 days) and IN (15 of 63 days) groups than in the placebo group (2 of 87 days, P < 0,001). Postvaccination geometric mean titers (GMT, arithmetic transformation of log 2) of RSV-specific neutralizing antibody were significantly increased in the IT H-RSV group compared with postplacebo GMTs at 1 week (72 vs. 6.7, P < 0.03). By the second week postinoculation both H-RSV-infected groups had comparable levels of RSV-specific neutralizing antibody titers and had significantly greater GMTs for the second through to the fourth week than the placebo group (144, 128, and 4.8, respectively P < 0.0008). Bacterial isolates of the upper airway were comparable among the three groups. Histopathology at day 28 postinoculation was unremarkable for the three study groups. The development of overt clinical illness in lambs inoculated with H-RSV suggests that the H-RSV lamb model may be used to delineate the pathogenesis of lung injury of H-RSV infection.