Respiratory syncytial virus infection activates STAT signaling in human epithelial cells

Acute respiratory syncytial virus (RSV) infection causes airway inflammation and exacerbates asthma, but the mechanism of inflammation is poorly understood. The role of the STAT-signaling pathway in RSV infection in epithelial cells was examined in this study. DNA microarray analyses of RSV-infected...

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Bibliographic Details
Published in:	Biochemical and biophysical research communications Vol. 306; no. 2; pp. 616 - 622
Main Authors:	Kong, Xiaoyuan, San Juan, Homero, Kumar, Mukesh, Behera, Aruna K, Mohapatra, Alexander, Hellermann, Gary R, Mane, Srikant, Lockey, Richard F, Mohapatra, Shyam S
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 27-06-2003
Subjects:	Active Transport, Cell Nucleus Cell Line DNA - metabolism Electrophoresis, Polyacrylamide Gel Epithelial Cells - metabolism Gene expression Genes, Reporter Heparin - metabolism Heparin Lyase - metabolism Humans Immunoblotting Immunohistochemistry Interferon-Stimulated Gene Factor 3 Interleukin-6 - metabolism Microarray Microscopy, Fluorescence Models, Genetic Oligonucleotide Array Sequence Analysis Phosphorylation Promoter Regions, Genetic Respiratory syncytial virus Respiratory Syncytial Virus Infections - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Signal Transduction STAT Transcription factors Transcription Factors - metabolism Transcription, Genetic Transfection Tumor Cells, Cultured Signal transduction STAT Transcription factors Respiratory syncytial virus Microarray Gene expression
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Summary:	Acute respiratory syncytial virus (RSV) infection causes airway inflammation and exacerbates asthma, but the mechanism of inflammation is poorly understood. The role of the STAT-signaling pathway in RSV infection in epithelial cells was examined in this study. DNA microarray analyses of RSV-infected human alveolar type II (A549) epithelial cells identified several genes whose expression was altered from −5.5 to +56.4-fold. Four of the highly expressed genes contained STAT-binding elements. In A549 and normal human bronchial epithelial cells (NHBE), RSV induced phosphorylation and nuclear translocation of STAT-1α that was abrogated when RSV attachment was blocked. Treatment with a JAK-2 inhibitor or transfection with dominant-negative STAT-1α blocked STAT-1α activation and RSV infection. RSV also activated STAT-3 and IL-6 specific antibodies blocked this activation. Thus, activation of the STAT-1α and STAT-3 pathways play a role in RSV infection.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0006-291X 1090-2104
DOI:	10.1016/S0006-291X(03)01008-8