RRC ID 43366
Author Uetani K, Hiroi M, Meguro T, Ogawa H, Kamisako T, Ohmori Y, Erzurum SC.
Title Influenza A virus abrogates IFN-gamma response in respiratory epithelial cells by disruption of the Jak/Stat pathway.
Journal Eur J Immunol
Abstract The innate immunity to viral infections induces a potent antiviral response mediated by interferons (IFN). Although IFN-gamma is detected during the acute stages of illness in the upper respiratory tract secretions and in the serum of influenza A virus-infected individuals, control of influenza A virus is not dependent upon IFN-gamma as evidenced by studies using anti-IFN-gamma Ab and IFN-gamma(-/-) mice. Thus, we hypothesized that IFN-gamma is not critical in host survival because influenza A virus has mechanisms to evade the antiviral activity of IFN-gamma. To test this, A549 cells, an epithelial cell line derived from lung adenocarcinoma, were infected with influenza virus strain A/Aichi/2/68 (H3N2) (Aichi) and/or stimulated with IFN-gamma to detect IFN-gamma-stimulated MHC class II expression. Influenza A virus infection inhibited IFN-gamma-induced up-regulation of HLA-DRalpha mRNA and the IFN-gamma induction of class II transactivator (CIITA), an obligate mediator of MHC class II expression. Nuclear translocation of Stat1alpha upon IFN-gamma stimulation was significantly inhibited in influenza A virus-infected cells and this was associated with a decrease in Tyr701 and Ser727 phosphorylation of Stat1alpha. Thus, influenza A virus subverts antiviral host defense mediated by IFN-gamma through effects on the intracellular signaling pathways.
Volume 38(6)
Pages 1559-73
Published 2008-6-1
DOI 10.1002/eji.200737045
PMID 18493979
MeSH Blotting, Western Cell Line, Tumor Epithelial Cells / drug effects Epithelial Cells / metabolism Epithelial Cells / virology* GTP-Binding Proteins / genetics Gene Expression / drug effects HLA-DR Antigens / genetics Humans Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics Influenza A virus / immunology* Intercellular Adhesion Molecule-1 / genetics Interferon Regulatory Factor-1 / genetics Interferon-Stimulated Gene Factor 3 / metabolism Interferon-alpha / pharmacology Interferon-gamma / pharmacology* Janus Kinase 1 / genetics Janus Kinase 1 / metabolism* Microscopy, Confocal Models, Biological NF-kappa B / metabolism Nuclear Proteins / genetics Nuclear Proteins / metabolism Phosphorylation / drug effects Receptors, Interferon / genetics Receptors, Interferon / metabolism Respiratory Mucosa / pathology Reverse Transcriptase Polymerase Chain Reaction STAT1 Transcription Factor / metabolism* Signal Transduction / drug effects* Trans-Activators / genetics Trans-Activators / metabolism
IF 4.695
Times Cited 32
Human and Animal Cells