Journal of NeuroVirology

, Volume 19, Issue 1, pp 75–81

Varicella zoster virus infection of highly pure terminally differentiated human neurons

Authors

  • Xiaoli Yu
    • Department of NeurologyUniversity of Colorado Denver School of Medicine
  • Scott Seitz
    • Department of NeurologyUniversity of Colorado Denver School of Medicine
  • Tiffany Pointon
    • Department of NeurologyUniversity of Colorado Denver School of Medicine
  • Jacqueline L. Bowlin
    • Department of NeurologyUniversity of Colorado Denver School of Medicine
  • Randall J. Cohrs
    • Department of NeurologyUniversity of Colorado Denver School of Medicine
  • Stipan Jonjić
    • Department of Histology and EmbryologyUniversity of Rijeka
  • Jürgen Haas
    • Division of Pathway MedicineUniversity of Edinburgh
  • Mary Wellish
    • Department of NeurologyUniversity of Colorado Denver School of Medicine
    • Department of NeurologyUniversity of Colorado Denver School of Medicine
    • Department of MicrobiologyUniversity of Colorado Denver School of Medicine
Article

DOI: 10.1007/s13365-012-0142-x

Cite this article as:
Yu, X., Seitz, S., Pointon, T. et al. J. Neurovirol. (2013) 19: 75. doi:10.1007/s13365-012-0142-x

Abstract

In vitro analyses of varicella zoster virus (VZV) reactivation from latency in human ganglia have been hampered by the inability to isolate virus by explantation or cocultivation techniques. Furthermore, attempts to study interaction of VZV with neurons in experimentally infected ganglion cells in vitro have been impaired by the presence of nonneuronal cells, which become productively infected and destroy the cultures. We have developed an in vitro model of VZV infection in which highly pure (>95 %) terminally differentiated human neurons derived from pluripotent stem cells were infected with VZV. At 2 weeks post-infection, infected neurons appeared healthy compared to VZV-infected human fetal lung fibroblasts (HFLs), which developed a cytopathic effect (CPE) within 1 week. Tissue culture medium from VZV-infected neurons did not produce a CPE in uninfected HFLs and did not contain PCR-amplifiable VZV DNA, but cocultivation of infected neurons with uninfected HFLs did produce a CPE. The nonproductively infected neurons contained multiple regions of the VZV genome, as well as transcripts and proteins corresponding to VZV immediate-early, early, and late genes. No markers of the apoptotic caspase cascade were detected in healthy-appearing VZV-infected neurons. VZV infection of highly pure terminally differentiated human neurons provides a unique in vitro system to study the VZV-neuronal relationship and the potential to investigate mechanisms of VZV reactivation.

Keywords

Varicella zoster virusHuman neuronsNonproductive infection

Copyright information

© Journal of NeuroVirology, Inc. 2012