Abstract |
Infection of cells by vesicular stomatitis virus (VSV) results in the inhibition of host transcription. We show in this study that infection of HeLa cells with VSV leads to a strongly diminished activation of STAT3 and STAT1 by the inflammatory cytokine IL-6. This effect was mimicked by forced expression of a single viral protein, the matrix (M)- protein of VSV, which blocked STAT activation via chimeric receptors containing the cytoplasmic domain of the IL-6 signal transducer gp130. Western blot analysis revealed that VSV M- protein did not inhibit the nuclear translocation of activated STAT3 but did inhibit its tyrosine phosphorylation. Inhibition of STAT activation was not dependent on tyrosine 759 of the IL-6 signal transducer gp130, suggesting that the inhibitory action of VSV M- protein is not mediated by the induction of the suppressor of cytokine signaling 3. VSV M- protein inhibited gene transcription from cotransfected alpha(2)-macroglobulin or antichymotrypsin promoter/ luciferase reporter constructs which contain STAT3-binding sites. However, transcription from a STAT5-dependent construct was not negatively affected. In conclusion, our data suggest that infection by VSV and specifically overexpression of the viral M-protein interferes with an important signaling pathway necessary for triggering antiviral and inflammatory responses.
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Authors | L Terstegen, P Gatsios, S Ludwig, S Pleschka, W Jahnen-Dechent, P C Heinrich, L Graeve |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 167
Issue 9
Pg. 5209-16
(Nov 01 2001)
ISSN: 0022-1767 [Print] United States |
PMID | 11673534
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD
- DNA-Binding Proteins
- IL6ST protein, human
- Interleukin-6
- Membrane Glycoproteins
- STAT3 Transcription Factor
- STAT3 protein, human
- Trans-Activators
- Viral Matrix Proteins
- Cytokine Receptor gp130
- Tyrosine
- JNK Mitogen-Activated Protein Kinases
- MAP Kinase Kinase 4
- Mitogen-Activated Protein Kinase Kinases
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Topics |
- Antigens, CD
(physiology)
- Cytokine Receptor gp130
- DNA-Binding Proteins
(physiology)
- HeLa Cells
- Humans
- Interleukin-6
(pharmacology)
- JNK Mitogen-Activated Protein Kinases
- MAP Kinase Kinase 4
- Membrane Glycoproteins
(physiology)
- Mitogen-Activated Protein Kinase Kinases
(physiology)
- Phosphorylation
- STAT3 Transcription Factor
- Trans-Activators
(physiology)
- Transcription, Genetic
- Tyrosine
(metabolism)
- Vesicular stomatitis Indiana virus
(pathogenicity)
- Viral Matrix Proteins
(toxicity)
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