Human Respiratory Syncytial Virus Memphis 37 Causes Acute Respiratory Disease in Perinatal Lamb Lung
Human Respiratory Syncytial Virus Memphis 37 Causes Acute Respiratory Disease in Perinatal Lamb Lung
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DOI：
10.1089/biores.2013.0044
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发表时间：
2014-04-01
影响因子：
--
通讯作者：
Ackermann, Mark R.
中科院分区：
文献类型：
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作者：
Derscheid, Rachel J.;van Geelen, Albert;Ackermann, Mark R.
呼吸道合胞病毒（RSV）是工业化国家婴幼儿因呼吸道疾病住院的主要原因。人们对严重疾病的机制缺乏了解，治疗方案也有限，没有一种是完全令人满意的。这部分是由于缺乏模拟婴儿中度至重度疾病的围产期RSV感染的相关动物模型。我们和其他人已经证明，无论是牛或人的RSV A2株在围产期羔羊轻度疾病。人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上呼吸道疾病。我们假设RSV的孟菲斯37株会感染围产期羔羊并产生与人类婴儿相似的临床疾病。对围产期（3- 5日龄）羔羊鼻内接种2 mL/ml 1 x 10（5）病灶形成单位（FFU）/mL（n = 2）或2.1 x 10（8）FFU/mL（n = 3）RSV孟菲斯37。评估临床体征、大体和组织学病变以及免疫和炎症反应。孟菲斯37引起中度至重度大体和组织学病变，沿着巨噬细胞炎性蛋白mRNA表达增加。临床上，五只感染羔羊中有四只的呼气努力轻度至重度增加。鼻内给药RSV毒株孟菲斯37感染新生羔羊，其大体、组织学和免疫应答与在人类婴儿中观察到的相似。
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 mL/nostril of 1 x 10(5) focus-forming units (FFU)/mL (n = 2) or 2.1 x 10(8) 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.