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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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Autores principales: Angelova, Magdalena, Zwezdaryk, Kevin, Ferris, MaryBeth, Shan, Bin, Morris, Cindy A., Sullivan, Deborah E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469659/
https://www.ncbi.nlm.nih.gov/pubmed/23071438
http://dx.doi.org/10.1371/journal.ppat.1002959
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author Angelova, Magdalena
Zwezdaryk, Kevin
Ferris, MaryBeth
Shan, Bin
Morris, Cindy A.
Sullivan, Deborah E.
author_facet Angelova, Magdalena
Zwezdaryk, Kevin
Ferris, MaryBeth
Shan, Bin
Morris, Cindy A.
Sullivan, Deborah E.
author_sort Angelova, Magdalena
collection PubMed
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.
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spelling pubmed-34696592012-10-15 Human Cytomegalovirus Infection Dysregulates the Canonical Wnt/β-catenin Signaling Pathway Angelova, Magdalena Zwezdaryk, Kevin Ferris, MaryBeth Shan, Bin Morris, Cindy A. Sullivan, Deborah E. PLoS Pathog Research Article 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. Public Library of Science 2012-10-11 /pmc/articles/PMC3469659/ /pubmed/23071438 http://dx.doi.org/10.1371/journal.ppat.1002959 Text en © 2012 Angelova et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Angelova, Magdalena
Zwezdaryk, Kevin
Ferris, MaryBeth
Shan, Bin
Morris, Cindy A.
Sullivan, Deborah E.
Human Cytomegalovirus Infection Dysregulates the Canonical Wnt/β-catenin Signaling Pathway
title 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_short Human Cytomegalovirus Infection Dysregulates the Canonical Wnt/β-catenin Signaling Pathway
title_sort human cytomegalovirus infection dysregulates the canonical wnt/β-catenin signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469659/
https://www.ncbi.nlm.nih.gov/pubmed/23071438
http://dx.doi.org/10.1371/journal.ppat.1002959
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