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

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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.

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Acknowledgements

We thank Gyöngyi Ábrahám for expert technical assistance. This study was supported by grants ETT/398/2003 from the Hungarian Ministry of Health, Social and Family Affairs and OTKA/T043144 from the Hungarian Scientific Research Fund. Klára Megyeri is a recipient of a grant from the Bolyai Foundation.

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Authors and Affiliations

  1. Department of Ophthalmology, University of Szeged, Korányi fasor 10–11, 6720, Szeged, Hungary

    Éva Gallyas

  2. Department of Medical Biology, University of Szeged, Somogyi Béla u. 4, 6720, Szeged, Hungary

    György Seprényi

  3. Department of Dermatology and Allergology, University of Szeged, Korányi fasor 6, 6720, Szeged, Hungary

    Eniko Sonkoly & Lajos Kemény

  4. Department of Medical Microbiology and Immunobiology, University of Szeged, Dóm tér 10, 6720, Szeged, Hungary

    Yvette Mándi & Klára Megyeri

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  1. Éva Gallyas
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  2. György Seprényi
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  4. Yvette Mándi
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Correspondence to Klára Megyeri.

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Gallyas, É., Seprényi, G., Sonkoly, E. et al. Vesicular stomatitis virus induces apoptosis in the Wong–Kilbourne derivative of the Chang conjunctival cell line. Graefe's Arch Clin Exp Ophthalmo 244, 717–724 (2006). https://doi.org/10.1007/s00417-005-0162-9

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  • DOI: https://doi.org/10.1007/s00417-005-0162-9

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