The vesicular stomatitis virus matrix protein inhibits glycoprotein 130-dependent STAT activation.
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.
Terstegen
L
L
Institut für Biochemie and Interdisziplinäres Zentrum für Klinische Forschung Biomat., Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
Gatsios
P
P
Ludwig
S
S
Pleschka
S
S
Jahnen-Dechent
W
W
Heinrich
P C
PC
Graeve
L
L
D015703:Antigens, CD / Q000502:physiology*; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D008562:Membrane Glycoproteins / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D010766:Phosphorylation; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000472:pathogenicity*; D014763:Viral Matrix Proteins / Q000633:toxicity*
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D014763:Viral Matrix Proteins; D050822:Cytokine Receptor gp130; D014443:Tyrosine; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases