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RNA-seq analysis of host and viral gene expression highlights interaction between Varicella Zoster virus and Keratinocyte differentiation

Title: RNA-seq analysis of host and viral gene expression highlights interaction between Varicella Zoster virus and Keratinocyte differentiation
Authors: Jones, M
Dry, IR
Frampton, D
Singh, M
Kanda, RK
Yee, MB
Kellam, P
Hollinshead, M
Kinchington, PR
O'Toole, EA
Breuer, J
Item Type: Journal Article
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.
Issue Date: 30-Jan-2014
Date of Acceptance: 9-Dec-2013
URI: http://hdl.handle.net/10044/1/69472
DOI: https://dx.doi.org/10.1371/journal.ppat.1003896
ISSN: 1553-7366
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS Pathogens
Volume: 10
Issue: 1
Copyright Statement: © 2014 Jones et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
CELL-CELL CONTACT
SCID-HU MOUSE
HUMAN SKIN
IN-VITRO
GLYCOPROTEIN-C
NETHERTON-SYNDROME
EPIDERMAL-CELLS
STEM-CELLS
T-CELLS
PROTEIN
Cell Differentiation
Chickenpox
Female
Gene Expression Regulation, Viral
Herpesvirus 3, Human
Humans
Keratinocytes
Male
RNA, Viral
Sequence Analysis, RNA
Viral Proteins
Virus Replication
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Article Number: e1003896
Online Publication Date: 2014-01-30
Appears in Collections:Department of Medicine



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