Human respiratory syncytial virus A2 strain replicates and induces innate immune responses by respiratory epithelia of neonatal lambs.

Human respiratory syncytial virus A2 strain replicates and induces innate immune responses by respiratory epithelia of neonatal lambs.
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DOI:
10.1111/j.1365-2613.2009.00643.x
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发表时间:
2009-08
影响因子:
3
通讯作者:
Ackermann M
Ackermann M
中科院分区:
医学4区
文献类型:
--
作者:
Olivier A;Gallup J;de Macedo MM;Varga SM;Ackermann M

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人类呼吸道合胞病毒(RSV)是一种肺炎病毒,会导致早产儿和足月儿严重的呼吸道疾病。我们的假设是,RSV的一种常见毒株A2株会感染新生羔羊,引起肺部病理,并改变呼吸道上皮先天免疫反应,类似于人类新生儿的RSV感染。对2日龄至3日龄新生羔羊进行呼吸道合胞病毒A2株呼吸道合胞病毒感染。分别于接种后第3、6、14天处死羔羊。接种后6d组的肺部病变为典型的呼吸道合胞病毒感染,包括伴有中性粒细胞的毛细支气管炎和轻度细支气管周间质性肺炎。用定量聚合酶链式反应(QPCR)和免疫组织化学方法分别检测RSV的mRNA和抗原的表达,并在第6天检测抗原的表达。实时荧光定量聚合酶链式反应(Real-Time-qPCR)检测表面活性蛋白A和D、绵羊β-防御素-1和甲状腺转录因子1mRNA的表达。呼吸道合胞病毒感染后第6天,肺表面活性物质A和D的mRNA表达显著增加。绵羊β-防御素-1和甲状腺转录因子-1mRNA的表达没有显著变化。本研究表明新生羔羊可感染呼吸道合胞病毒A2株,其肺部病理与人类婴幼儿呼吸道合胞病毒感染相似,从而使新生羔羊成为研究疾病发病机制和治疗方法的有用动物模型。RSV感染导致羔羊表面活性蛋白A和D表达增加,这也可能是新生儿感染的一个重要特征。
Human respiratory syncytial virus (RSV) is a pneumovirus that causes significant respiratory disease in pre-mature and full-term infants. It was our hypothesis that a common strain of RSV, strain A2, would infect, cause pulmonary pathology, and alter respiratory epithelial innate immune responses in neonatal lambs similarly to RSV infection in human neonates. Newborn lambs between 2 and 3 days of age were inoculated intrabronchially with RSV strain A2. The lambs were sacrificed at days 3, 6, and 14 days post-inoculation. Pulmonary lesions in the 6-day post-inoculation group were typical of RSV infection including bronchiolitis with neutrophils and mild peribronchiolar interstitial pneumonia. RSV mRNA and antigen were detected by qPCR and immunohistochemistry respectively with peak mRNA levels and antigen at day 6. Expression of surfactant proteins A and D, sheep beta-defensin-1 and thyroid transcription factor 1 mRNA were also assessed by real-time qPCR. There was a significant increase in surfactant A and D mRNA expression in RSV-infected animals at day 6 post-inoculation. There were no significant changes in sheep beta-defensin-1 and thyroid transcription factor-1 mRNA expression. This study shows that neonatal lambs can be infected with RSV strain A2 and the pulmonary pathology mimics that of RSV infection in human infants thereby making the neonatal lamb a useful animal model to study disease pathogenesis and therapeutics. RSV infection induces increased expression of surfactant proteins A and D in lambs, which may also be an important feature of infection in newborn infants.
DOI: 10.1074/jbc.m404296200
发表时间: 2004-08-13
影响因子: 4.8
作者:
Davé, V;Childs, T;Whitsett, JA
通讯作者: Whitsett, JA
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发表时间: 2003-01-01
影响因子: 9.4
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DOI: 10.1128/cdli.11.3.599-607.2004
发表时间: 2004-05-01
期刊: CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子: --
作者:
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通讯作者: Ackermann, MR
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发表时间: 1993-03-01
影响因子: 3.1
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通讯作者: PIEDRA, PT
DOI: 10.1002/ar.1092050304
发表时间: 1983-01-01
期刊: ANATOMICAL RECORD
影响因子: --
作者:
MARIASSY, AT;PLOPPER, CG
通讯作者: PLOPPER, CG