Vesicular stomatitis virus induces apoptosis in the Wong-Kilbourne derivative of the Chang conjunctival cell line

Éva Gallyas, György Seprényi, Eniko Sonkoly, Yvette Mándi, Lajos Kemény, Klára Megyeri

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Abstract

Background: Virotherapy represents a novel therapeutic modality for the treatment of malignant diseases. Vesicular stomatitis virus (VSV) has been shown to exert antitumor effect in several tumor types. Since the potential oncolytic activity of VSV has not yet been evaluated in epithelial tumors of the conjunctiva, we set out to investigate the susceptibility of the immortalized Wong-Kilbourne derivative of the Chang conjunctival cell line (WK) to VSV and analyze the role of apoptosis in VSV-mediated induction of cell death. Methods: WK cells were infected with VSV at various multiplicities and maintained for different periods of time. VSV-infected cells were analyzed by inverted microscopy for the development of cytopathic effects (CPE). Virus replication was measured by indirect immunofluorescence assay, Western blot analysis and plaque titration. The apoptotic response of the infected cells was quantitated by ELISA detecting the enrichment of nucleosomes in the cytoplasm. Western blot analysis was used to determine the levels of Bcl-2 and Bax proteins. Results: The WK cell line was highly permissive to VSV replication and was highly susceptible for the CPE of this virus. VSV infection elicited the apoptotic death of WK cells. Mock-infected cells exhibited endogenous expression of Bcl-2 and p21 Bax proteins. VSV infection caused a significant decrease in the expression level of Bcl-2. Moreover, in parallel with a slight decrease in the level of p21 Bax, p18 Bax protein accumulated in VSV-infected WK cells. Conclusions: VSV is a powerful inducer of apoptosis in immortalized WK cells. The VSV-mediated alterations in the expressions of Bcl-2 and Bax proteins may play important roles in the apoptotic responses of infected cells and may also sensitize to other apoptotic stimuli. This virus may possess oncolytic activity in epithelial tumors of the conjunctiva.

Original languageEnglish
Pages (from-to)717-724
Number of pages8
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume244
Issue number6
DOIs
Publication statusPublished - Jun 1 2006

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Keywords

  • Apoptosis
  • Bax
  • Bcl-2
  • Vesicular stomatitis virus
  • WK conjunctival cell line

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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