Placental pericytes and cytomegalovirus infectivity: Implications for HCMV placental pathology and congenital disease

David M. Aronoff, Hernan Correa, Lisa M. Rogers, Ravit Arav-Boger, Donald J. Alcendor

Research output: Contribution to journalArticlepeer-review

Abstract

Problem: Placental pericytes are essential for placental microvascular function, stability, and integrity. Mechanisms of human cytomegalovirus (HCMV) pathogenesis incorporating placental pericytes are unknown. Method of Study: HCMV-infected placental tissue was stained by dual-labeled immunohistochemistry. Primary placental pericytes, cytotrophoblasts, and villous fibroblasts were exposed to HCMV; and infectivity was analyzed by microscopy and immunofluorescence. Cytokine expression was examined by Luminex assay. A HCMV-GFP recombinant virus was used to examine replication kinetics. Results: Immunohistochemistry showed HCMV in trophoblast and the villous core with T-cell and macrophage infiltration. Primary HCMV isolate from a patient (SBCMV)- infected pericytes showed dysregulation of proinflammatory and angiogenic cytokines when compared to control cells. A tri-cell model of the villous floor showed a unique expression profile. Finally, we show pericytes infected in vivo with HCMV in placental tissue from a congenitally infected child. Conclusion: Placental pericytes support HCMV replication, inducing proinflammatory and angiogenic cytokines that likely contribute to viral dissemination, placenta inflammation, and dysregulation of placental angiogenesis.

Original languageEnglish (US)
Article numbere12728
JournalAmerican Journal of Reproductive Immunology
Volume78
Issue number3
DOIs
StatePublished - Sep 2017

Keywords

  • angiogenesis
  • cytokines
  • human cytomegalovirus
  • inflammation
  • virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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