Retrograde axonal transport of VZV: Kinetic studies in hESC-derived neurons

Sergei Grigoryan, Paul R. Kinchington, In Hong Yang, Anca Selariu, Hua Zhu, Michael Yee, Ronald S. Goldstein

Research output: Contribution to journalArticlepeer-review

Abstract

Retrograde axonal transport of the neurotropic alphaherpesvirus Varicella zoster virus (VZV) from vesicles at the skin results in sensory neuron infection and establishment of latency. Reactivation from latency leads to painful herpes zoster. The lack of a suitable animal model of these processes for the highly human-restricted VZV has resulted in a dearth of knowledge regarding the axonal transport of VZV. We recently demonstrated VZV infection of distal axons, leading to subsequent capsid transport to the neuronal somata, and replication and release of infectious virus using a new model based on neurons derived from human embryonic stem cells (hESC). In the present study, we perform a kinetic analysis of the retrograde transport of green fluorescent protein-tagged ORF23 in VZV capsids using hESC-derived neurons compartmentalized microfluidic chambers and time-lapse video microscopy. The motion of the VZV was discontinuous, showing net retrograde movement with numerous short pauses and reversals in direction. Velocities measured were higher 1 h after infection than 6 h after infection, while run lengths were similar at both time points. The hESC-derived neuron model was also used to show that reduced neuronal spread by a VZV loss-of-function mutant for ORF7 is not due to the prevention of axonal infection and transport of the virus to the neuronal somata. hESC-derived neurons are, therefore, a powerful model for studying axonal transport of VZV and molecular characteristics of neuronal infection.

Original languageEnglish (US)
Pages (from-to)462-470
Number of pages9
JournalJournal of neurovirology
Volume18
Issue number6
DOIs
StatePublished - Dec 2012

Keywords

  • Alphaherpesvirus
  • Axonal transport
  • Human embryonic stem cells
  • Varicella zoster virus

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

Fingerprint

Dive into the research topics of 'Retrograde axonal transport of VZV: Kinetic studies in hESC-derived neurons'. Together they form a unique fingerprint.

Cite this