title: Varicella zoster virus infection of malignant glioma cell cultures: a new candidate for oncolytic virotherapy?
abstract: BACKGROUND
  Glioblastoma multiforme is a highly aggressive tumor with a median survival of 14 months despite all standard therapies. Focusing on alternative treatment strategies, we evaluated the oncolytic potential of varicella zoster virus (VZV) in malignant glioma cell cultures.
  
  
  METHODS
  Replication of wildtype and mutant VZV was comparatively analyzed in glioma cell lines (U87, U251 and U373) and in primary malignant glioma cells (n=10) in vitro by infectious foci assay, immunofluorescence microscopy and western blot analysis. Additionally, the tumor-targeting potential of VZV-infected human mesenchymal stem cells was evaluated.
  
  
  RESULTS
  VZV replicated efficiently in all the glioma cells studied here followed by rapid oncolysis in vitro. The attenuated vaccine VZV mutant rOKA/ORF63rev[T171] exhibited most efficient replication. Human mesenchymal stem cells were found suitable for targeting VZV to sites of tumor growth.
  
  
  CONCLUSIONS
  VZV exhibits an intrinsic oncolytic potential in malignant glioma cell cultures and might be a novel candidate for virotherapy in glioblastoma multiforme.
authors.affiliation: Department of Neurosurgery, Hospital of the University of Munich, Grosshadern, Munich, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Leske
authors.forename: Rudolf
authors.initials: R
authors.lastname: Haase
authors.forename: Florian
authors.initials: F
authors.lastname: Restle
authors.forename: Christian
authors.initials: C
authors.lastname: Schichor
authors.forename: Valerie
authors.initials: V
authors.lastname: Albrecht
authors.forename: Maria G
authors.initials: MG
authors.lastname: Vizoso Pinto
authors.forename: Joerg C
authors.initials: JC
authors.lastname: Tonn
authors.forename: Armin
authors.initials: A
authors.lastname: Baiker
authors.forename: Niklas
authors.initials: N
authors.lastname: Thon
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy / Q000821:virology*; D045744:Cell Line, Tumor; D005910:Glioma / Q000473:pathology / Q000628:therapy / Q000821:virology*; D014645:Herpesvirus 3, Human / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D050130:Oncolytic Virotherapy; D014779:Virus Replication