title: The 72-kilodalton IE-1 protein of human cytomegalovirus (HCMV) is a potent inducer of connective tissue growth factor (CTGF) in human dermal fibroblasts.
abstract: Latent human cytomegalovirus (HCMV) infection has been implicated in diseases characterized by tissue remodeling. Because of recent evidence indicating the possibility of a partial HCMV reactivation, the purpose of this study was to examine the role of the HCMV immediate early (IE) genes in the regulation of extracellular matrix (ECM) related host genes. Adenoviral vector expressing IE1 was generated to allow efficient gene delivery into human fibroblasts. IE1 stimulated the prolonged expression of connective tissue growth factor (CTGF) and TIMP1. IE1-dependent stimulation of CTGF was partially mediated by TGF-beta. Moreover, whereas collagenous proteins and collagen type 1 mRNA were only transiently induced by IE1 in the majority of fibroblasts, in selected fibroblast strains IE1 induced persistent ECM upregulation for up to 120 hours. This study suggests that transient or limited HCMV reactivation may play a direct role in abnormal matrix remodeling in GVHD, scleroderma, atherosclerosis and other HCMV-linked diseases.
authors.affiliation: Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA. markiewi@musc.edu
authors.forename: M
authors.initials: M
authors.lastname: Markiewicz
authors.forename: E A
authors.initials: EA
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Rubinchik
authors.forename: J Y
authors.initials: JY
authors.lastname: Dong
authors.forename: M
authors.initials: M
authors.lastname: Trojanowska
authors.forename: E C
authors.initials: EC
authors.lastname: LeRoy
mesh_terms: D018929:Cell Culture Techniques; D055513:Connective Tissue Growth Factor; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology; D020405:Dermis / Q000276:immunology*; D005109:Extracellular Matrix / Q000276:immunology; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: C526317:CCN2 protein, human; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D014764:Viral Proteins; D055513:Connective Tissue Growth Factor