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 |
4.404
|
Times Cited |
32
|
WOS Category
|
IMMUNOLOGY
|
Resource |
Human and Animal Cells |
MDCK(RCB0995)
A549(RCB0098) |