Activation of Peroxisome Proliferator-Activated Receptor Gamma by Human Cytomegalovirus for De Novo Replication Impairs Migration and Invasiveness of Cytotrophoblasts from Early Placentas
- 15 March 2010
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 84 (6), 2946-2954
- https://doi.org/10.1128/jvi.01779-09
Abstract
Human cytomegalovirus (HCMV) contributes to pathogenic processes in immunosuppressed individuals, in fetuses, and in neonates. In the present report, by using reporter gene activation assays and confocal microscopy in the presence of a specific antagonist, we show for the first time that HCMV infection induces peroxisome proliferator-activated receptor gamma (PPARγ) transcriptional activity in infected cells. We demonstrate that the PPARγ antagonist dramatically impairs virus production and that the major immediate-early promoter contains PPAR response elements able to bind PPARγ, as assessed by electrophoretic mobility shift and chromatin immunoprecipitation assays. Due to the key role of PPARγ in placentation and its specific trophoblast expression within the human placenta, we then provided evidence that by activating PPARγ human cytomegalovirus dramatically impaired early human trophoblast migration and invasiveness, as assessed by using well-established in vitro models of invasive trophoblast, i.e., primary cultures of extravillous cytotrophoblasts (EVCT) isolated from first-trimester placentas and the EVCT-derived cell line HIPEC. Our data provide new clues to explain how early infection during pregnancy could impair implantation and placentation and therefore embryonic development.Keywords
This publication has 29 references indexed in Scilit:
- Autorepression of the Human Cytomegalovirus Major Immediate-Early Promoter/Enhancer at Late Times of Infection Is Mediated by the Recruitment of Chromatin Remodeling Enzymes by IE86Journal of Virology, 2006
- Peroxisome Proliferator-Activated Receptor Subtype- and Cell-Type-Specific Activation of Genomic Target Genes upon Adenoviral Transgene DeliveryMolecular and Cellular Biology, 2006
- Combinatorial roles of nuclear receptors in inflammation and immunityNature Reviews Immunology, 2005
- Promoter usage and alternative splicingCurrent Opinion in Cell Biology, 2005
- A Cyclooxygenase-2 Homologue Encoded by Rhesus Cytomegalovirus Is a Determinant for Endothelial Cell TropismJournal of Virology, 2004
- Human Cytomegalovirus Carries a Cell-Derived Phospholipase A2 Required for InfectivityJournal of Virology, 2004
- The human semaphorin 6B gene is down regulated by PPARsGenomics, 2004
- Human Cytomegalovirus Interleukin-10 Downregulates Metalloproteinase Activity and Impairs Endothelial Cell Migration and Placental Cytotrophoblast Invasiveness In VitroJournal of Virology, 2004
- Peroxisome Proliferator-Activated Receptors: Nuclear Control of MetabolismEndocrine Reviews, 1999
- Human cytomegalovirus stimulates arachidonic acid metabolism through pathways that are affected by inhibitors of phospholipase A2 and protein kinase CBiochemical and Biophysical Research Communications, 1990