Human Cytomegalovirus Infection Dysregulates the Canonical Wnt/β-catenin Signaling Pathway

PLoS Pathogens

Bin Shan¹  Magdalena Angelova²  MaryBeth Ferris²  Deborah E. Sullivan²  Kevin Zwezdaryk²  Cindy A. Morris² 

[1] Department of Medicine, Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America;Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America

关键词: Wnt signaling cascade;    Human cytomegalovirus;    Cytomegalovirus infection;    Proteasomes;    Cyclins;    Opportunistic infections;    Cell differentiation;    Signal inhibition;   

DOI  :  10.1371/journal.ppat.1002959

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY