Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.

Varicella Zoster Virus (VZV), the alphaherpesvirus that causes varicella upon primary infection and Herpes zoster (shingles) following reactivation in latently infected neurons, is known to be fusogenic. It forms polynuclear syncytia in culture, in varicella skin lesions and in infected fetal human...

Full description

Bibliographic Details
Main Authors: Sergei Grigoryan, Michael B Yee, Yair Glick, Doron Gerber, Eldad Kepten, Yuval Garini, In Hong Yang, Paul R Kinchington, Ronald S Goldstein
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4431828?pdf=render
_version_ 1818552856321458176
author Sergei Grigoryan
Michael B Yee
Yair Glick
Doron Gerber
Eldad Kepten
Yuval Garini
In Hong Yang
Paul R Kinchington
Ronald S Goldstein
author_facet Sergei Grigoryan
Michael B Yee
Yair Glick
Doron Gerber
Eldad Kepten
Yuval Garini
In Hong Yang
Paul R Kinchington
Ronald S Goldstein
author_sort Sergei Grigoryan
collection DOAJ
description Varicella Zoster Virus (VZV), the alphaherpesvirus that causes varicella upon primary infection and Herpes zoster (shingles) following reactivation in latently infected neurons, is known to be fusogenic. It forms polynuclear syncytia in culture, in varicella skin lesions and in infected fetal human ganglia xenografted to mice. After axonal infection using VZV expressing green fluorescent protein (GFP) in compartmentalized microfluidic cultures there is diffuse filling of axons with GFP as well as punctate fluorescence corresponding to capsids. Use of viruses with fluorescent fusions to VZV proteins reveals that both proteins encoded by VZV genes and those of the infecting cell are transferred in bulk from infecting non-neuronal cells to axons. Similar transfer of protein to axons was observed following cell associated HSV1 infection. Fluorescence recovery after photobleaching (FRAP) experiments provide evidence that this transfer is by diffusion of proteins from the infecting cells into axons. Time-lapse movies and immunocytochemical experiments in co-cultures demonstrate that non-neuronal cells fuse with neuronal somata and proteins from both cell types are present in the syncytia formed. The fusogenic nature of VZV therefore may enable not only conventional entry of virions and capsids into axonal endings in the skin by classical entry mechanisms, but also by cytoplasmic fusion that permits viral protein transfer to neurons in bulk.
first_indexed 2024-12-12T09:18:33Z
format Article
id doaj.art-f976b34342164c7f8f7c940cc5ab889f
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-12T09:18:33Z
publishDate 2015-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-f976b34342164c7f8f7c940cc5ab889f2022-12-22T00:29:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012608110.1371/journal.pone.0126081Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.Sergei GrigoryanMichael B YeeYair GlickDoron GerberEldad KeptenYuval GariniIn Hong YangPaul R KinchingtonRonald S GoldsteinVaricella Zoster Virus (VZV), the alphaherpesvirus that causes varicella upon primary infection and Herpes zoster (shingles) following reactivation in latently infected neurons, is known to be fusogenic. It forms polynuclear syncytia in culture, in varicella skin lesions and in infected fetal human ganglia xenografted to mice. After axonal infection using VZV expressing green fluorescent protein (GFP) in compartmentalized microfluidic cultures there is diffuse filling of axons with GFP as well as punctate fluorescence corresponding to capsids. Use of viruses with fluorescent fusions to VZV proteins reveals that both proteins encoded by VZV genes and those of the infecting cell are transferred in bulk from infecting non-neuronal cells to axons. Similar transfer of protein to axons was observed following cell associated HSV1 infection. Fluorescence recovery after photobleaching (FRAP) experiments provide evidence that this transfer is by diffusion of proteins from the infecting cells into axons. Time-lapse movies and immunocytochemical experiments in co-cultures demonstrate that non-neuronal cells fuse with neuronal somata and proteins from both cell types are present in the syncytia formed. The fusogenic nature of VZV therefore may enable not only conventional entry of virions and capsids into axonal endings in the skin by classical entry mechanisms, but also by cytoplasmic fusion that permits viral protein transfer to neurons in bulk.http://europepmc.org/articles/PMC4431828?pdf=render
spellingShingle Sergei Grigoryan
Michael B Yee
Yair Glick
Doron Gerber
Eldad Kepten
Yuval Garini
In Hong Yang
Paul R Kinchington
Ronald S Goldstein
Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.
PLoS ONE
title Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.
title_full Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.
title_fullStr Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.
title_full_unstemmed Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.
title_short Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.
title_sort direct transfer of viral and cellular proteins from varicella zoster virus infected non neuronal cells to human axons
url http://europepmc.org/articles/PMC4431828?pdf=render
work_keys_str_mv AT sergeigrigoryan directtransferofviralandcellularproteinsfromvaricellazostervirusinfectednonneuronalcellstohumanaxons
AT michaelbyee directtransferofviralandcellularproteinsfromvaricellazostervirusinfectednonneuronalcellstohumanaxons
AT yairglick directtransferofviralandcellularproteinsfromvaricellazostervirusinfectednonneuronalcellstohumanaxons
AT dorongerber directtransferofviralandcellularproteinsfromvaricellazostervirusinfectednonneuronalcellstohumanaxons
AT eldadkepten directtransferofviralandcellularproteinsfromvaricellazostervirusinfectednonneuronalcellstohumanaxons
AT yuvalgarini directtransferofviralandcellularproteinsfromvaricellazostervirusinfectednonneuronalcellstohumanaxons
AT inhongyang directtransferofviralandcellularproteinsfromvaricellazostervirusinfectednonneuronalcellstohumanaxons
AT paulrkinchington directtransferofviralandcellularproteinsfromvaricellazostervirusinfectednonneuronalcellstohumanaxons
AT ronaldsgoldstein directtransferofviralandcellularproteinsfromvaricellazostervirusinfectednonneuronalcellstohumanaxons