| RRC ID |
17620
|
| 著者 |
Markus A, Grigoryan S, Sloutskin A, Yee MB, Zhu H, Yang IH, Thakor NV, Sarid R, Kinchington PR, Goldstein RS.
|
| タイトル |
Varicella-zoster virus (VZV) infection of neurons derived from human embryonic stem cells: direct demonstration of axonal infection, transport of VZV, and productive neuronal infection.
|
| ジャーナル |
J Virol
|
| Abstract |
Study of the human neurotrophic herpesvirus varicella-zoster virus (VZV) and of its ability to infect neurons has been severely limited by strict viral human tropism and limited availability of human neurons for experimentation. Human embryonic stem cells (hESC) can be differentiated to all the cell types of the body including neurons and are therefore a potentially unlimited source of human neurons to study their interactions with human neurotropic viruses. We report here reproducible infection of hESC-derived neurons by cell-associated green fluorescent protein (GFP)-expressing VZV. hESC-derived neurons expressed GFP within 2 days after incubation with mitotically inhibited MeWo cells infected with recombinant VZV expressing GFP as GFP fusions to VZV proteins or under an independent promoter. VZV infection was confirmed by immunostaining for immediate-early and viral capsid proteins. Infection of hESC-derived neurons was productive, resulting in release into the medium of infectious virions that appeared fully assembled when observed by electron microscopy. We also demonstrated, for the first time, VZV infection of axons and retrograde transport from axons to neuronal cell bodies using compartmented microfluidic chambers. The use of hESC-derived human neurons in conjunction with fluorescently tagged VZV shows great promise for the study of VZV neuronal infection and axonal transport and has potential for the establishment of a model for VZV latency in human neurons.
|
| 巻・号 |
85(13)
|
| ページ |
6220-33
|
| 公開日 |
2011-7-1
|
| DOI |
10.1128/JVI.02396-10
|
| PII |
JVI.02396-10
|
| PMID |
21525353
|
| PMC |
PMC3126485
|
| MeSH |
Axonal Transport
Axons / ultrastructure
Axons / virology*
Capsid / metabolism
Capsid / ultrastructure
Cell Differentiation*
Cells, Cultured
Embryonic Stem Cells / cytology*
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Herpesvirus 3, Human / genetics
Herpesvirus 3, Human / pathogenicity*
Herpesvirus 3, Human / physiology
Humans
Microscopy, Electron, Transmission
Neurons / ultrastructure
Neurons / virology*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Viral Proteins / genetics
Viral Proteins / metabolism
Virion / metabolism
Virion / ultrastructure
Virus Release
|
| IF |
4.501
|
| 引用数 |
46
|
|
WOS 分野
|
VIROLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-G2/PA6(RCB1127) |
