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Human trophoblasts confer resistance to viruses implicated in perinatal infection.

Authors
  • Bayer, Avraham1
  • Delorme-Axford, Elizabeth2
  • Sleigher, Christie3
  • Frey, Teryl K3
  • Trobaugh, Derek W4
  • Klimstra, William B4
  • Emert-Sedlak, Lori A2
  • Smithgall, Thomas E5
  • Kinchington, Paul R6
  • Vadia, Stephen7
  • Seveau, Stephanie3
  • Boyle, Jon P8
  • Coyne, Carolyn B2
  • Sadovsky, Yoel1, 2
  • 1 Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • 2 Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
  • 3 Georgia State University, Biology Department, Atlanta, GA, 30303, USA. , (Georgia)
  • 4 Center for Vaccine Research, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • 5 Drug Discovery Institute, Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
  • 6 Department of Ophthalmology, and Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
  • 7 Center for Microbial Interface Biology and Department of Microbial Infection and Immunity, Ohio State University, Columbus, OH 43210, USA.
  • 8 Department of Biological Sciences, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Type
Published Article
Journal
American journal of obstetrics and gynecology
Publication Date
Jan 01, 2015
Volume
212
Issue
1
Identifiers
DOI: 10.1016/j.ajog.2014.07.060
PMID: 25108145
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Primary human trophoblasts were previously shown to be resistant to viral infection, and able to confer this resistance to nontrophoblast cells. Can trophoblasts protect nontrophoblastic cells from infection by viruses or other intracellular pathogens that are implicated in perinatal infection? Isolated primary term human trophoblasts were cultured for 48-72 hours. Diverse nonplacental human cell lines (U2OS, human foreskin fibroblast, TZM-bl, MeWo, and Caco-2) were preexposed to either trophoblast conditioned medium, nonconditioned medium, or miR-517-3p for 24 hours. Cells were infected with several viral and nonviral pathogens known to be associated with perinatal infections. Cellular infection was defined and quantified by plaque assays, luciferase assays, microscopy, and/or colonization assays. Differences in infection were assessed by Student t test or analysis of variance with Bonferroni correction. Infection by rubella and other togaviruses, human immunodeficiency virus-1, and varicella zoster was attenuated in cells preexposed to trophoblast-conditioned medium (P < .05), and a partial effect by the chromosome 19 microRNA miR-517-3p on specific pathogens. The conditioned medium had no effect on infection by Toxoplasma gondii or Listeria monocytogenes. Our findings indicate that medium conditioned by primary human trophoblasts attenuates viral infection in nontrophoblastic cells. Our data point to a trophoblast-specific antiviral effect that may be exploited therapeutically. Copyright © 2015 Elsevier Inc. All rights reserved.

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