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Placental pericytes and cytomegalovirus infectivity: Implications for HCMV placental pathology and congenital disease. Am J Reprod Immunol 2017 Sep;78(3)

Date

07/26/2017

Pubmed ID

28741727

Pubmed Central ID

PMC5561471

DOI

10.1111/aji.12728

Scopus ID

2-s2.0-85026411248 (requires institutional sign-in at Scopus site)   17 Citations

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.

Author List

Aronoff DM, Correa H, Rogers LM, Arav-Boger R, Alcendor DJ

Author

Ravit Boger MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cells, Cultured
Chorionic Villi
Coculture Techniques
Cytokines
Cytomegalovirus
Cytomegalovirus Infections
Female
Fibroblasts
Humans
Immunohistochemistry
Pericytes
Placenta
Pregnancy
Trophoblasts
Virus Replication