Human cytomegalovirus infection dysregulates the canonical Wnt/β-catenin signaling pathway.
Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus that currently infects a large percentage of the world population. Although usually asymptomatic in healthy individuals, HCMV infection during pregnancy may cause spontaneous abortions, premature delivery, or permanent neurological disabilitie...
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2012-01-01
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doaj-2e1538893811447fa3dabf5fe4f22ac92020-11-25T00:34:39ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-01810e100295910.1371/journal.ppat.1002959Human cytomegalovirus infection dysregulates the canonical Wnt/β-catenin signaling pathway.Magdalena AngelovaKevin ZwezdarykMaryBeth FerrisBin ShanCindy A MorrisDeborah E SullivanHuman Cytomegalovirus (HCMV) is a ubiquitous herpesvirus that currently infects a large percentage of the world population. Although usually asymptomatic in healthy individuals, HCMV infection during pregnancy may cause spontaneous abortions, premature delivery, or permanent neurological disabilities in infants infected in utero. During infection, the virus exerts control over a multitude of host signaling pathways. Wnt/β-catenin signaling, an essential pathway involved in cell cycle control, differentiation, embryonic development, placentation and metastasis, is frequently dysregulated by viruses. How HCMV infection affects this critical pathway is not currently known. In this study, we demonstrate that HCMV dysregulates Wnt/β-catenin signaling in dermal fibroblasts and human placental extravillous trophoblasts. Infection inhibits Wnt-induced transcriptional activity of β-catenin and expression of β-catenin target genes in these cells. HCMV infection leads to β-catenin protein accumulation in a discrete juxtanuclear region. Levels of β-catenin in membrane-associated and cytosolic pools, as well as nuclear β-catenin, are reduced after infection; while transcription of the β-catenin gene is unchanged, suggesting enhanced degradation. Given the critical role of Wnt/β-catenin signaling in cellular processes, these findings represent a novel and important mechanism whereby HCMV disrupts normal cellular function.http://europepmc.org/articles/PMC3469659?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Magdalena Angelova Kevin Zwezdaryk MaryBeth Ferris Bin Shan Cindy A Morris Deborah E Sullivan |
spellingShingle |
Magdalena Angelova Kevin Zwezdaryk MaryBeth Ferris Bin Shan Cindy A Morris Deborah E Sullivan Human cytomegalovirus infection dysregulates the canonical Wnt/β-catenin signaling pathway. PLoS Pathogens |
author_facet |
Magdalena Angelova Kevin Zwezdaryk MaryBeth Ferris Bin Shan Cindy A Morris Deborah E Sullivan |
author_sort |
Magdalena Angelova |
title |
Human cytomegalovirus infection dysregulates the canonical Wnt/β-catenin signaling pathway. |
title_short |
Human cytomegalovirus infection dysregulates the canonical Wnt/β-catenin signaling pathway. |
title_full |
Human cytomegalovirus infection dysregulates the canonical Wnt/β-catenin signaling pathway. |
title_fullStr |
Human cytomegalovirus infection dysregulates the canonical Wnt/β-catenin signaling pathway. |
title_full_unstemmed |
Human cytomegalovirus infection dysregulates the canonical Wnt/β-catenin signaling pathway. |
title_sort |
human cytomegalovirus infection dysregulates the canonical wnt/β-catenin signaling pathway. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2012-01-01 |
description |
Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus that currently infects a large percentage of the world population. Although usually asymptomatic in healthy individuals, HCMV infection during pregnancy may cause spontaneous abortions, premature delivery, or permanent neurological disabilities in infants infected in utero. During infection, the virus exerts control over a multitude of host signaling pathways. Wnt/β-catenin signaling, an essential pathway involved in cell cycle control, differentiation, embryonic development, placentation and metastasis, is frequently dysregulated by viruses. How HCMV infection affects this critical pathway is not currently known. In this study, we demonstrate that HCMV dysregulates Wnt/β-catenin signaling in dermal fibroblasts and human placental extravillous trophoblasts. Infection inhibits Wnt-induced transcriptional activity of β-catenin and expression of β-catenin target genes in these cells. HCMV infection leads to β-catenin protein accumulation in a discrete juxtanuclear region. Levels of β-catenin in membrane-associated and cytosolic pools, as well as nuclear β-catenin, are reduced after infection; while transcription of the β-catenin gene is unchanged, suggesting enhanced degradation. Given the critical role of Wnt/β-catenin signaling in cellular processes, these findings represent a novel and important mechanism whereby HCMV disrupts normal cellular function. |
url |
http://europepmc.org/articles/PMC3469659?pdf=render |
work_keys_str_mv |
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