RESPIRATORY SYNCYTIAL VIRUS-REPLICATION IN HUMAN LUNG EPITHELIAL-CELLS - INHIBITION BY TUMOR-NECROSIS-FACTOR-ALPHA AND INTERFERON-BETA
RESPIRATORY SYNCYTIAL VIRUS-REPLICATION IN HUMAN LUNG EPITHELIAL-CELLS - INHIBITION BY TUMOR-NECROSIS-FACTOR-ALPHA AND INTERFERON-BETA
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DOI：
10.1164/ajrccm.152.4.7551395
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发表时间：
1995-10-01
影响因子：
24.7
通讯作者：
PANUSKA, JR
中科院分区：
文献类型：
--
作者：
MEROLLA, R;REBERT, NA;PANUSKA, JR
呼吸道合胞病毒（RSV）是引起儿童严重肺部疾病的主要病原体。RSV最初在呼吸道中有效复制，但在正常儿童感染后7至21天无法检测到，这表明尚未确定的内在细胞机制可能限制病毒复制。为了提供一个体外模型来检验限制RSV复制的机制，将三种人肺上皮细胞系暴露于RSV体外，病毒复制以剂量和时间依赖的方式进行，尽管效率低于高度允许的CV-1细胞系（猴肾上皮细胞）。肿瘤坏死因子α (TNF α)和/或干扰素β (IFN β)以剂量和时间依赖的方式显著抑制RSV复制。TNF α联合IFN β基本上终止了RSV在A549上皮细胞中的复制。TNF α和/或IFN β不会引起细胞膜损伤、细胞裂解或抑制细胞蛋白合成。rsv感染的人肺泡巨噬细胞产生TNF α，在共培养中不能有效感染肺上皮细胞。综上所述，这些研究表明内源性TNF α与外源性IFN β结合可以限制RSV在肺上皮中的复制。
Respiratory syncytial virus (RSV) is the major pathogen causing severe lung disease in children. RSV initially replicates efficiently in the respiratory tract but becomes undetectable by 7 to 21 d after infection in normal children, suggesting that intrinsic cellular mechanisms, as yet undefined, may restrict virus replication. To provide an in vitro model to examine mechanisms that restrict RSV replication, three human lung epithelial cell lines were exposed to RSV in vitro and virus replication proceeded in a dose- and time-dependent manner, although less efficiently than the highly permissive CV-1 cell line (monkey kidney epithelial cell). Tumor necrosis factor alpha (TNF alpha) and/or interferon beta (IFN beta) markedly inhibited RSV replication in a dose- and time-dependent manner. TNF alpha combined with IFN beta essentially aborted RSV replication in A549 epithelial cells. TNF alpha and/or IFN beta did not induce cell membrane damage, cause cell lysis, or inhibit cellular protein synthesis. RSV-infected human alveolar macrophages, which produce TNF alpha, failed to productively infect lung epithelial cells in co-culture. Together these studies suggest that endogenous TNF alpha coupled with exogenous IFN beta could restrict RSV replication in lung epithelium.