title: Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection.
abstract: During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZIKV may bypass the placenta to reach the fetus. This led us to investigate ZIKV infection of primary human trophoblasts (PHTs), which are the barrier cells of the placenta. We discovered that PHT cells from full-term placentas are refractory to ZIKV infection. In addition, medium from uninfected PHT cells protects non-placental cells from ZIKV infection. PHT cells constitutively release the type III interferon (IFN) IFNλ1, which functions in both a paracrine and autocrine manner to protect trophoblast and non-trophoblast cells from ZIKV infection. Our data suggest that for ZIKV to access the fetal compartment, it must evade restriction by trophoblast-derived IFNλ1 and other trophoblast-specific antiviral factors and/or use alternative strategies to cross the placental barrier.
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Obstetrics, Gynecology, and Reproductive Science, 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: Nicholas J
authors.initials: NJ
authors.lastname: Lennemann
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Obstetrics, Gynecology, and Reproductive Science, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Yingshi
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Bramley
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Morosky
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Fundação Osvaldo Cruz - FIOCRUZ, Recife, Pernambuco 50670-420, Brazil.
authors.forename: Ernesto Torres De Azeved
authors.initials: ET
authors.lastname: Marques
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Cherry
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Obstetrics, Gynecology, and Reproductive Science, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: ysadovsky@mwri.magee.edu.
authors.forename: Yoel
authors.initials: Y
authors.lastname: Sadovsky
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Obstetrics, Gynecology, and Reproductive Science, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: coynec2@pitt.edu.
authors.forename: Carolyn B
authors.initials: CB
authors.lastname: Coyne
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005260:Female; D005315:Fetal Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007372:Interferons / Q000096:biosynthesis* / Q000276:immunology* / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008831:Microcephaly / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D010920:Placenta / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014709:Vero Cells; D000071244:Zika Virus / Q000187:drug effects / Q000276:immunology; D000071243:Zika Virus Infection / Q000276:immunology / Q000517:prevention & control*; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: IFNλ; Zika virus; placenta; trophoblasts; type III interferon; virus