Cytotrophoblasts infected with a pathogenic human cytomegalovirus strain dysregulate cell-matrix and cell-cell adhesion molecules: a quantitative analysis.
Studies of intrauterine human cytomegalovirus (CMV) infection have shown suppressed replication in the decidua and placenta of strongly seropositive women. Biopsy specimens often contain CMV virion glycoprotein B and DNA in syncytiotrophoblasts and villus core macrophages without productive infection. Focal replication occurs in placentas of women with low to moderate neutralizing antibody titres. Infected cytotrophoblasts downregulate key adhesion and immune molecules required for invasiveness and maternal immune tolerance and reduce matrix metalloproteinase-9 protein and activity, impairing degradation of the extracellular matrix. Here, we used flow cytometry and quantitative RT-PCR analyses to quantify differentiation molecules expressed in freshly isolated cytotrophoblasts purified from placentas at term and differentiating cells infected in vitro with VR1814, a pathogenic clinical strain. Cell surface proteins including E-cadherin, VE-cadherin, HLA-G, and CMV receptors--epidermal growth factor receptor and integrins beta1 and alphavbeta3--were expressed on purified cells, as were integrins alpha9 and beta6, which were not previously studied. Infected cytotrophoblasts dysregulate the levels of particular cell-matrix and cell-cell adhesion proteins and their transcripts. CMV replication in late gestation placentas with considerable reserves could deplete cytotrophoblast progenitors, thereby impairing syncytiotrophoblast development and increasing the risk of virus transmission to fetal blood vessels.
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Department of Cell and Tissue Biology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0512, USA.
McDonagh
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Kawakatsu
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Pereira
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D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D021982:Cell-Matrix Junctions / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000503:physiopathology*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005434:Flow Cytometry; D017930:Genes, Reporter; D006801:Humans; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011991:Receptors, Virus / Q000502:physiology; D014327:Trophoblasts / Q000821:virology*
D015815:Cell Adhesion Molecules; D011991:Receptors, Virus; D004247:DNA