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 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.
Kong
Xiaoyuan
X
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.
San Juan
Homero
H
Kumar
Mukesh
M
Behera
Aruna K
AK
Mohapatra
Alexander
A
Hellermann
Gary R
GR
Mane
Srikant
S
Lockey
Richard F
RF
Mohapatra
Shyam S
SS
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
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