title: Posttranslational modification of vesicular stomatitis virus glycoprotein, but not JNK inhibition, is the antiviral mechanism of SP600125.
abstract: Vesicular stomatitis virus (VSV), a negative-sense single-stranded-RNA rhabdovirus, is an extremely promising oncolytic agent for cancer treatment. Since oncolytic virotherapy is moving closer to clinical application, potentially synergistic combinations of oncolytic viruses and molecularly targeted antitumor agents are becoming a meaningful strategy for cancer treatment. Mitogen-activated protein kinase (MAPK) inhibitors have been shown to impair liver cell proliferation and tumor development, suggesting their potential use as therapeutic agents for hepatocellular carcinoma (HCC). In this work, we show that the impairment of MAPK in vitro did not interfere with the oncolytic properties of VSV in HCC cell lines. Moreover, the administration of MAPK inhibitors did not restore the responsiveness of HCC cells to alpha/beta interferon (IFN-α/β). In contrast to previous reports, we show that JNK inhibition by the inhibitor SP600125 is not responsible for VSV attenuation in HCC cells and that this compound acts by causing a posttranslational modification of the viral glycoprotein.
authors.affiliation: Department of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Marozin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Altomonte
authors.forename: Sibylle
authors.initials: S
authors.lastname: Apfel
authors.forename: Phat X
authors.initials: PX
authors.lastname: Dinh
authors.forename: Enrico N
authors.initials: EN
authors.lastname: De Toni
authors.forename: Antonia
authors.initials: A
authors.lastname: Rizzani
authors.forename: Andreas
authors.initials: A
authors.lastname: Nüssler
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.forename: Asit K
authors.initials: AK
authors.lastname: Pattnaik
authors.forename: Oliver
authors.initials: O
authors.lastname: Ebert
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D018116:Vesiculovirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014771:Virion / Q000187:drug effects; D057074:Virus Release / Q000187:drug effects
chemical_list: D000873:Anthracenes; D000998:Antiviral Agents; C028391:G protein, vesicular stomatitis virus; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C432165:pyrazolanthrone