title: The vesicular stomatitis virus matrix protein inhibits glycoprotein 130-dependent STAT activation.
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.
authors.affiliation: Institut für Biochemie and Interdisziplinäres Zentrum für Klinische Forschung Biomat., Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Terstegen
authors.forename: P
authors.initials: P
authors.lastname: Gatsios
authors.forename: S
authors.initials: S
authors.lastname: Ludwig
authors.forename: S
authors.initials: S
authors.lastname: Pleschka
authors.forename: W
authors.initials: W
authors.lastname: Jahnen-Dechent
authors.forename: P C
authors.initials: PC
authors.lastname: Heinrich
authors.forename: L
authors.initials: L
authors.lastname: Graeve
mesh_terms: 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*
chemical_list: 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