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RNA-seq Analysis of Host and Viral Gene Expression Highlights Interaction between Varicella Zoster Virus and Keratinocyte Differentiation

Jones, M and Dry, IR and Frampton, D and Singh, M and Kanda, RK and Yee, MB and Kellam, P and Hollinshead, M and Kinchington, PR and O'Toole, EA and Breuer, J (2014) RNA-seq Analysis of Host and Viral Gene Expression Highlights Interaction between Varicella Zoster Virus and Keratinocyte Differentiation. PLoS Pathogens, 10 (1). ISSN 1553-7366

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Abstract

Varicella zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterized by epidermal skin blistering. Using a calcium-induced keratinocyte differentiation model we investigated the interaction between epidermal differentiation and VZV infection. RNA-seq analysis showed that VZV infection has a profound effect on differentiating keratinocytes, altering the normal process of epidermal gene expression to generate a signature that resembles patterns of gene expression seen in both heritable and acquired skin-blistering disorders. Further investigation by real-time PCR, protein analysis and electron microscopy revealed that VZV specifically reduced expression of specific suprabasal cytokeratins and desmosomal proteins, leading to disruption of epidermal structure and function. These changes were accompanied by an upregulation of kallikreins and serine proteases. Taken together VZV infection promotes blistering and desquamation of the epidermis, both of which are necessary to the viral spread and pathogenesis. At the same time, analysis of the viral transcriptome provided evidence that VZV gene expression was significantly increased following calcium treatment of keratinocytes. Using reporter viruses and immunohistochemistry we confirmed that VZV gene and protein expression in skin is linked with cellular differentiation. These studies highlight the intimate host-pathogen interaction following VZV infection of skin and provide insight into the mechanisms by which VZV remodels the epidermal environment to promote its own replication and spread. © 2014 Jones et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Jones, M
Dry, IR
Frampton, D
Singh, M
Kanda, RK
Yee, MBMBY1@pitt.eduMBY1
Kellam, P
Hollinshead, M
Kinchington, PRkinch@pitt.eduKINCH
O'Toole, EA
Breuer, J
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorEverett, Roger D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 January 2014
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 10
Number: 1
DOI or Unique Handle: 10.1371/journal.ppat.1003896
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
School of Medicine > Ophthalmology
Refereed: Yes
ISSN: 1553-7366
Date Deposited: 01 Jul 2014 16:33
Last Modified: 04 Feb 2019 15:56
URI: http://d-scholarship.pitt.edu/id/eprint/22126

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