title: Respiratory syncytial virus infection activates STAT signaling in human epithelial cells.
abstract: 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-1alpha that was abrogated when RSV attachment was blocked. Treatment with a JAK-2 inhibitor or transfection with dominant-negative STAT-1alpha blocked STAT-1alpha activation and RSV infection. RSV also activated STAT-3 and IL-6 specific antibodies blocked this activation. Thus, activation of the STAT-1alpha and STAT-3 pathways play a role in RSV infection.
authors.affiliation: Division of Allergy and Immunology, The Joy McCann Culverhouse Airway Disease Center, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL 33612, USA.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Kong
authors.forename: Homero
authors.initials: H
authors.lastname: San Juan
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.forename: Aruna K
authors.initials: AK
authors.lastname: Behera
authors.forename: Alexander
authors.initials: A
authors.lastname: Mohapatra
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hellermann
authors.forename: Srikant
authors.initials: S
authors.lastname: Mane
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lockey
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Mohapatra
mesh_terms: D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000378:metabolism*; D017930:Genes, Reporter; D006493:Heparin / Q000378:metabolism; D019763:Heparin Lyase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D050832:Interferon-Stimulated Gene Factor 3; D015850:Interleukin-6 / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D050832:Interferon-Stimulated Gene Factor 3; D015850:Interleukin-6; D012333:RNA, Messenger; D014157:Transcription Factors; C079868:gamma interferon activation factor; D006493:Heparin; D004247:DNA; D019763:Heparin Lyase