Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

An In Vitro Model of Latency and Reactivation of Varicella Zoster Virus in Human Stem Cell-Derived Neurons

Markus, A and Lebenthal-Loinger, I and Yang, IH and Kinchington, PR and Goldstein, RS (2015) An In Vitro Model of Latency and Reactivation of Varicella Zoster Virus in Human Stem Cell-Derived Neurons. PLoS Pathogens, 11 (6). ISSN 1553-7366

[img]
Preview
PDF
Published Version
Available under License : See the attached license file.

Download (3MB)
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

Abstract

© 2015 Markus et al. Varicella zoster virus (VZV) latency in sensory and autonomic neurons has remained enigmatic and difficult to study, and experimental reactivation has not yet been achieved. We have previously shown that human embryonic stem cell (hESC)-derived neurons are permissive to a productive and spreading VZV infection. We now demonstrate that hESC-derived neurons can also host a persistent non-productive infection lasting for weeks which can subsequently be reactivated by multiple experimental stimuli. Quiescent infections were established by exposing neurons to low titer cell-free VZV either by using acyclovir or by infection of axons in compartmented microfluidic chambers without acyclovir. VZV DNA and low levels of viral transcription were detectable by qPCR for up to seven weeks. Quiescently-infected human neuronal cultures were induced to undergo renewed viral gene and protein expression by growth factor removal or by inhibition of PI3-Kinase activity. Strikingly, incubation of cultures induced to reactivate at a lower temperature (34°C) resulted in enhanced VZV reactivation, resulting in spreading, productive infections. Comparison of VZV genome transcription in quiescently-infected to productively-infected neurons using RNASeq revealed preferential transcription from specific genome regions, especially the duplicated regions. These experiments establish a powerful new system for modeling the VZV latent state, and reveal a potential role for temperature in VZV reactivation and disease.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Markus, A
Lebenthal-Loinger, I
Yang, IH
Kinchington, PRkinch@pitt.eduKINCH
Goldstein, RS
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorKalejta, Robert F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 January 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS Pathogens
Volume: 11
Number: 6
DOI or Unique Handle: 10.1371/journal.ppat.1004885
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
School of Medicine > Ophthalmology
Refereed: Yes
ISSN: 1553-7366
Date Deposited: 25 Jul 2016 17:13
Last Modified: 26 Jan 2019 10:55
URI: http://d-scholarship.pitt.edu/id/eprint/28575

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com


Actions (login required)

View Item View Item