Abstract
Clinical or laboratory evidence of varicella-zoster virus (VZV) infection has been consistently associated with lower glioma risk in case–control studies, suggesting a protective effect of VZV against glioma. We formulated the following explanatory hypotheses: reactivated VZV preferentially infects and kills gliomas compared to normal parenchyma; and VZV-specific cytotoxic T lymphocytes (CTL) cross-react with gliomas. We established an ex vivo model of VZV infection, which showed that glioma cell lines and primary astrocytes were equally permissive to VZV infection and had similar 15% average decrease in viability upon infection. In co-cultures, the relative growth of glioma cells and astrocytes was not affected by the VZV infection. However, VZV stimulated, but not mock stimulated, peripheral blood mononuclear cells from VZV-seropositive individuals recognized and killed HLA class I-matched glioma cells (mean±SE decrease in viability of 26 ± 12%, p = 0.04), but not matched astrocytes. VZV infection of the glioma cells did not affect the T cell-mediated killing. Taken together, these data suggest that ex vivo VZV infection has similar direct effects on glioma cells and astrocytes. The protective effect of prior VZV infection against the incidence of glioma may be mediated by CTL that recognizes epitopes shared by VZV and glioma cells.
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Acknowledgments
The authors thank Karen Helm for technical support and Drs. Ken Tyler, Margaret Wrensch, Joe Wiemels, John Wincke, and Myron Levin for critical review of the manuscript. This work was supported by P30 CA046934 grant to the University of Colorado Cancer Center and by a subcontract to R01CA52689 (PI Margaret Wrensch). The contents are the sole responsibility of the authors.
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Canniff, J., Donson, A.M., Foreman, N.K. et al. Cytotoxicity of glioblastoma cells mediated ex vivo by varicella-zoster virus-specific T cells. J. Neurovirol. 17, 448–454 (2011). https://doi.org/10.1007/s13365-011-0048-z
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DOI: https://doi.org/10.1007/s13365-011-0048-z