title: Human trophoblasts confer resistance to viruses implicated in perinatal infection.
abstract: OBJECTIVE
  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?
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Avraham
authors.initials: A
authors.lastname: Bayer
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Delorme-Axford
authors.affiliation: Georgia State University, Biology Department, Atlanta, GA, 30303, USA.
authors.forename: Christie
authors.initials: C
authors.lastname: Sleigher
authors.affiliation: Georgia State University, Biology Department, Atlanta, GA, 30303, USA.
authors.forename: Teryl K
authors.initials: TK
authors.lastname: Frey
authors.affiliation: Center for Vaccine Research, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Derek W
authors.initials: DW
authors.lastname: Trobaugh
authors.affiliation: Center for Vaccine Research, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Klimstra
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Emert-Sedlak
authors.affiliation: Drug Discovery Institute, Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Smithgall
authors.affiliation: Department of Ophthalmology, and Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kinchington
authors.affiliation: Center for Microbial Interface Biology and Department of Microbial Infection and Immunity, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Vadia
authors.affiliation: Georgia State University, Biology Department, Atlanta, GA, 30303, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Seveau
authors.affiliation: Department of Biological Sciences, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Jon P
authors.initials: JP
authors.lastname: Boyle
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Carolyn B
authors.initials: CB
authors.lastname: Coyne
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA.|Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Yoel
authors.initials: Y
authors.lastname: Sadovsky
mesh_terms: D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D060467:Disease Resistance; D005315:Fetal Diseases / Q000821:virology*; D006801:Humans; D007231:Infant, Newborn; D014327:Trophoblasts / Q000502:physiology*; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D017077:Culture Media, Conditioned
keywords: chromosome 19 microRNA cluster; conditioned medium; microRNA; trophoblasts; viruses
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