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01-12-2012

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

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

Published in: Journal of NeuroVirology | Issue 6/2012

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.

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Title: Retrograde axonal transport of VZV: kinetic studies in hESC-derived neurons
Authors: Sergei Grigoryan
Paul R. Kinchington
In Hong Yang
Anca Selariu
Hua Zhu
Michael Yee
Ronald S. Goldstein
Publication date: 01-12-2012
Publisher: Springer US
Published in: Journal of NeuroVirology / Issue 6/2012
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-012-0124-z

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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