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Human Respiratory Syncytial Virus Memphis 37 Causes Acute Respiratory Disease in Perinatal Lamb Lung

机译:人类呼吸道合胞病毒孟菲斯37导致围产期羔羊肺急性呼吸道疾病

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Respiratory syncytial virus (RSV) is the leading cause of hospitalization due to respiratory illness among infants and young children of industrialized countries. There is a lack of understanding of the severe disease mechanisms as well as limited treatment options, none of which are fully satisfactory. This is partly due to lack of a relevant animal model of perinatal RSV infection that mimics moderate to severe disease in infants. We and others have shown mild disease in perinatal lambs with either a bovine or a human A2 strain of RSV. The Memphis 37 clinical strain of human RSV has been used to produce mild to moderate upper respiratory disease in healthy adult volunteers. We hypothesized that the Memphis 37 strain of RSV would infect perinatal lambs and produce clinical disease similar to that in human infants. Perinatal (3- to 5-day-old) lambs were inoculated intranasally with 2?mLostril of 1×105 focus-forming units (FFU)/mL ( n =2) or 2.1×108 FFU/mL ( n =3) of RSV Memphis 37. Clinical signs, gross and histological lesions, and immune and inflammatory responses were assessed. Memphis 37 caused moderate to severe gross and histologic lesions along with increased mRNA expression of macrophage inflammatory protein. Clinically, four of the five infected lambs had a mild to severe increase in expiratory effort. Intranasally administered RSV strain Memphis 37 infects neonatal lambs with gross, histologic, and immune responses similar to those observed in human infants.
机译:呼吸道合胞病毒(RSV)是工业化国家的婴幼儿因呼吸系统疾病而住院的主要原因。缺乏对严重疾病机制的理解以及有限的治疗选择,这些都不是完全令人满意的。这部分是由于缺乏围生期RSV感染的相关动物模型,该模型模仿婴儿的中度至重度疾病。我们和其他人在牛或人的A2 RSV品系的围产羔羊中显示出轻度疾病。人类RSV的孟菲斯37临床株已用于在健康成人志愿者中产生轻度至中度的上呼吸道疾病。我们假设孟菲斯37株RSV会感染围产期羔羊,并产生与人类婴儿相似的临床疾病。围产期(3-5天大)羔羊鼻内接种2?mL /鼻孔的1×10 5 聚焦形成单位(FFU)/ mL(n = 2)或2.1× RSV孟菲斯为10 8 FFU / mL(n = 3)37.评估了临床体征,肉眼和组织学病变以及免疫和炎症反应。孟菲斯37引起中度至重度的肉眼和组织学损害,以及巨噬细胞炎症蛋白的mRNA表达增加。临床上,五只受感染的羔羊中有四只的呼气量有轻度至严重的增加。鼻内施用的RSV孟菲斯37株感染新生羔羊的肉眼,组织学和免疫反应与在人类婴儿中观察到的相似。

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