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Cell Host Microbe. 2016 May 11;19(5):705-12. doi: 10.1016/j.chom.2016.03.008. Epub 2016 Apr 5.

Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection.

Author information

1
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.
2
Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
3
Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Fundação Osvaldo Cruz - FIOCRUZ, Recife, Pernambuco 50670-420, Brazil.
4
Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
5
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.
6
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.

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.

KEYWORDS:

IFNλ; Zika virus; placenta; trophoblasts; type III interferon; virus

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PMID:
27066743
PMCID:
PMC4866896
DOI:
10.1016/j.chom.2016.03.008
[Indexed for MEDLINE]
Free PMC Article

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