Cell cycle progression or translation control is not essential for vesicular stomatitis virus oncolysis of hepatocellular carcinoma

Sabrina Marozin, Enrico N. de Toni, Antonia Rizzani, Jennifer Altomonte, Alexandra Junger, Günter Schneider, Wolfgang E. Thasler, Nobuyuki Kato, Roland M. Schmid, Oliver Ebert

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The intrinsic oncolytic specificity of vesicular stomatitis virus (VSV) is currently being exploited to develop alternative therapeutic strategies for hepatocellular carcinoma (HCC). Identifying key regulators in diverse transduction pathways that define VSV oncolysis in cancer cells represents a fundamental prerequisite to engineering more effective oncolytic viral vectors and adjusting combination therapies. After having identified defects in the signalling cascade of type I interferon induction, responsible for attenuated antiviral responses in human HCC cell lines, we have now investigated the role of cell proliferation and translation initiation. Cell cycle progression and translation initiation factors eIF4E and eIF2Bε have been recently identified as key regulators of VSV permissiveness in T-lymphocytes and immortalized mouse embryonic fibroblasts, respectively. Here, we show that in HCC, decrease of cell proliferation by cell cycle inhibitors or siRNA-mediated reduction of G(1) cyclin-dependent kinase activities (CDK4) or cyclin D1 protein expression, do not significantly alter viral growth. Additionally, we demonstrate that translation initiation factors eIF4E and eIF2Bε are negligible in sustaining VSV replication in HCC. Taken together, these results indicate that cellular proliferation and the initiation phase of cellular protein synthesis are not essential for successful VSV oncolysis of HCC. Moreover, our observations indicate the importance of cell-type specificity for VSV oncolysis, an important aspect to be considered in virotherapy applications in the future.

Original languageEnglish
Article numbere10988
JournalPLoS One
Volume5
Issue number6
DOIs
Publication statusPublished - 2010

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Vesiculovirus
Vesicular Stomatitis
hepatoma
Viruses
translation (genetics)
Hepatocellular Carcinoma
cell cycle
Cell Cycle
Cells
cell proliferation
Peptide Initiation Factors
Cell Proliferation
Cell proliferation
protein synthesis
Permissiveness
CDC2 Protein Kinase
Interferon Type I
D1 protein
therapeutics
T-cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Marozin, S., de Toni, E. N., Rizzani, A., Altomonte, J., Junger, A., Schneider, G., ... Ebert, O. (2010). Cell cycle progression or translation control is not essential for vesicular stomatitis virus oncolysis of hepatocellular carcinoma. PLoS One, 5(6), [e10988]. https://doi.org/10.1371/journal.pone.0010988

Cell cycle progression or translation control is not essential for vesicular stomatitis virus oncolysis of hepatocellular carcinoma. / Marozin, Sabrina; de Toni, Enrico N.; Rizzani, Antonia; Altomonte, Jennifer; Junger, Alexandra; Schneider, Günter; Thasler, Wolfgang E.; Kato, Nobuyuki; Schmid, Roland M.; Ebert, Oliver.

In: PLoS One, Vol. 5, No. 6, e10988, 2010.

Research output: Contribution to journalArticle

Marozin, S, de Toni, EN, Rizzani, A, Altomonte, J, Junger, A, Schneider, G, Thasler, WE, Kato, N, Schmid, RM & Ebert, O 2010, 'Cell cycle progression or translation control is not essential for vesicular stomatitis virus oncolysis of hepatocellular carcinoma', PLoS One, vol. 5, no. 6, e10988. https://doi.org/10.1371/journal.pone.0010988
Marozin, Sabrina ; de Toni, Enrico N. ; Rizzani, Antonia ; Altomonte, Jennifer ; Junger, Alexandra ; Schneider, Günter ; Thasler, Wolfgang E. ; Kato, Nobuyuki ; Schmid, Roland M. ; Ebert, Oliver. / Cell cycle progression or translation control is not essential for vesicular stomatitis virus oncolysis of hepatocellular carcinoma. In: PLoS One. 2010 ; Vol. 5, No. 6.
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