gms | German Medical Science

59th Annual Meeting of the German Society of Neurosurgery (DGNC)
3rd Joint Meeting with the Italian Neurosurgical Society (SINch)

German Society of Neurosurgery (DGNC)

1 - 4 June 2008, Würzburg

In vitro investigation of Varizella Zoster Virus as an oncolytic virus in glioblastoma therapy

Untersuchung der Eignung des Varizella-Zoster Virus als onkolytisches Virus in der Therapie von Glioblastomen

Meeting Abstract

  • corresponding author N. Thon - Department of Neurosurgery, University Hospital Großhadern, Munich
  • H. Leske - Department of Neurosurgery, University Hospital Großhadern, Munich
  • C. Schichor - Department of Neurosurgery, University Hospital Großhadern, Munich
  • J.-C. Tonn - Department of Neurosurgery, University Hospital Großhadern, Munich
  • R. Goldbrunner - Department of Neurosurgery, University Hospital Großhadern, Munich
  • A. Baiker - Max v. Pettenkofer Institute, Ludwig-Maximilians-University, Munich

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocDI.03.10

The electronic version of this article is the complete one and can be found online at:

Published: May 30, 2008

© 2008 Thon et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Varizella Zoster Virus (VZV) is an oncolytic virus solely replicating by cell-cell fusion processes. Recently, it has been shown that VZV is suitable for tumor therapy in malignant melanomas. Focusing on a future oncolytic therapy for malignant gliomas, aim of the following study was to asses permissive VZV replication in glioma cell lines and primary glioblastoma cell cultures in vitro.

Methods: Three gliomas cell lines (U87, U252, U373) and six primary cell cultures from human glioblastoma specimens have been tested for permissive cellular VZV replication in vitro. An established melanoma in vitro model has been used as positive control, three normal brain cell cultures (NBC) as negative controls. Since bone-morrow derived human mesenchymal stem cells (hMSC) are regarded as potential carriers of oncolytic therapy, three hMSC cultures were included in this study. Infection rates have been qualitatively and quantitatively evaluated by cellular expression of early (e.g. ORF63) and late (e.g. ORF68) viral proteins using immunocytochemistry. Oncolytic potency has been evaluated by cell counting and comparative morphometric culture analysis in simultaneously VZV infected glioma cells, hMSCs and normal brain derived cells in a time dependent protocol.

Results: Except for U87 cell line, permissive VZV replication has been verified in all glioma cell cultures tested including all primary cultures (8/9). Efficient total oncolytic cell death was detected within 6±3 days after VZV infection. Interestingly, plaque formation and syncytial fusion, which are characteristic for melanoma VZV replication, rarely occurred within glioma cell lines. Cell cultures harvested from normal brain specimens also exhibited ORF63/ORF68 expression, however, showed delayed single cell death (16±4 d after VZV infection). Interestingly, besides established VZV infected Melanoma cells permissive VZV replicating hMSC have also been highly suitable for cellular vehicles in glioma cell infection.

Conclusions: Wild-type VZV efficiently replicate within glioma cell cultures causing broad oncolytic cell death in vitro. The underlying mechanisms causing infections devoid of characteristic plaque formation are still unknown. Since hMSC are known to have an intrinsic tumor cell tropism autologous VZV-replicating hMSC could be applicable as cellular vehicles for local oncolytic glioma cell infection. Further investigations have to address sufficient glioma cell selectivity in VZV replication with respect to the normal brain parenchyma.