Posttranslational modification of vesicular stomatitis virus glycoprotein, but not JNK inhibition, is the antiviral mechanism of SP600125

Sabrina Marozin, Jennifer Altomonte, Sibylle Apfel, Phat X. Dinh, Enrico N. De Toni, Antonia Rizzani, Andreas Nüssler, Nobuyuki Kato, Roland M. Schmid, Asit K Pattnaik, Oliver Ebert

Research output: Contribution to journalArticle

4 Citations (Scopus)

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. Mitogenactivated 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/ß). 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.

Original languageEnglish (US)
Pages (from-to)4844-4855
Number of pages12
JournalJournal of virology
Volume86
Issue number9
DOIs
StatePublished - May 1 2012

Fingerprint

Vesiculovirus
Vesicular Stomatitis
post-translational modification
hepatoma
Post Translational Protein Processing
mitogen-activated protein kinase
Antiviral Agents
glycoproteins
Hepatocellular Carcinoma
Glycoproteins
protein kinases
Viruses
Protein Kinase Inhibitors
neoplasms
Oncolytic Virotherapy
Rhabdoviridae
Oncolytic Viruses
interferon-beta
Neoplasms
antineoplastic agents

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Posttranslational modification of vesicular stomatitis virus glycoprotein, but not JNK inhibition, is the antiviral mechanism of SP600125. / Marozin, Sabrina; Altomonte, Jennifer; Apfel, Sibylle; Dinh, Phat X.; De Toni, Enrico N.; Rizzani, Antonia; Nüssler, Andreas; Kato, Nobuyuki; Schmid, Roland M.; Pattnaik, Asit K; Ebert, Oliver.

In: Journal of virology, Vol. 86, No. 9, 01.05.2012, p. 4844-4855.

Research output: Contribution to journalArticle

Marozin, S, Altomonte, J, Apfel, S, Dinh, PX, De Toni, EN, Rizzani, A, Nüssler, A, Kato, N, Schmid, RM, Pattnaik, AK & Ebert, O 2012, 'Posttranslational modification of vesicular stomatitis virus glycoprotein, but not JNK inhibition, is the antiviral mechanism of SP600125', Journal of virology, vol. 86, no. 9, pp. 4844-4855. https://doi.org/10.1128/JVI.06649-11
Marozin, Sabrina ; Altomonte, Jennifer ; Apfel, Sibylle ; Dinh, Phat X. ; De Toni, Enrico N. ; Rizzani, Antonia ; Nüssler, Andreas ; Kato, Nobuyuki ; Schmid, Roland M. ; Pattnaik, Asit K ; Ebert, Oliver. / Posttranslational modification of vesicular stomatitis virus glycoprotein, but not JNK inhibition, is the antiviral mechanism of SP600125. In: Journal of virology. 2012 ; Vol. 86, No. 9. pp. 4844-4855.
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