Respiratory syncytial virus persistence in the lungs correlates with airway hyperreactivity in the mouse model.

Respiratory syncytial virus persistence in the lungs correlates with airway hyperreactivity in the mouse model.
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DOI:
10.1086/592714
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发表时间:
2008-11-15
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Mejias A
Mejias A
中科院分区:
其他
文献类型:
--
作者:
Estripeaut D;Torres JP;Somers CS;Tagliabue C;Khokhar S;Bhoj VG;Grube SM;Wozniakowski A;Gomez AM;Ramilo O;Jafri HS;Mejias A

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先前在小鼠中的研究表明,呼吸道合胞病毒(RSV)感染与RSV RNA持续存在相关。本研究旨在描述RSV RNA持续存在的意义及其与RSV诱导的慢性气道疾病的关系。用活RSV、UV光处理的RSV、热灭活的RSV或培养基接种小鼠。在接种后第1、5和42天采集支气管-肺泡灌洗液样本和肺标本,以评估肺部炎症,肺白细胞介素(IL)-4,IL-5,IL-15和干扰素(IFN)-γ的mRNA表达;通过培养和实时聚合酶链反应(PCR)评估RSV载量,并与肺功能相关。在感染的急性期,如培养和PCR所示,接种活RSV的小鼠的RSV载量显著较高。在第42天,仅在接种活的或UV光处理的RSV的小鼠中仍可检测到RSV RNA。在接种活RSV的小鼠中,肺炎症、IFN-γ:IL-4 mRNA表达比率、气道阻塞(AO)和气道高反应性(AHR)显著增加。第5天的AO和第42天的AHR与肺样品中的RSV RNA拷贝数显著相关。活RSV感染诱导的急性和慢性气道疾病与主要Th-1免疫应答和RSV RNA持续存在相关,与肺功能异常显著相关。
Previous studies in mice showed that respiratory syncytial virus (RSV) infection was associated with RSV RNA persistence. This study was designed to characterize the significance of RSV RNA persistence and its relation to RSV-induced chronic airway disease. Mice were inoculated with live RSV, UV light–treated RSV, heat-inactivated RSV, or medium. Bronchoal-veolar lavage fluid samples were obtained and lung specimens were harvested on days 1, 5, and 42 after inoculation to assess lung inflammation, lung mRNA expression of interleukin (IL)–4, IL-5, IL-15, and interferon (IFN)–γ; RSV loads were assessed by culture and real-time polymerase chain reaction (PCR) and correlated with pulmonary function. During the acute phase of infection, RSV loads as indicated by culture and PCR were significantly higher in mice inoculated with live RSV. On day 42, RSV RNA remained detectable only in mice inoculated with live or UV light–treated RSV. Lung inflammation, IFN-γ:IL-4 mRNA expression ratios, airway obstruction (AO), and airway hyperreactivity (AHR) were significantly increased in mice inoculated with live RSV. AO on day 5 and AHR on day 42 were significantly correlated with RSV RNA copy number in lung samples. Infection with live RSV induced acute and chronic airway disease that was associated with a predominantly Th-1 immune response and RSV RNA persistence that significantly correlated with pulmonary function abnormalities.
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