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2017-04-04
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TYPE III INTERFERONS PRODUCED BY HUMAN PLACENTAL TROPHOBLASTS CONFER PROTECTION AGAINST ZIKA VIRUS INFECTION
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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) IFNl1, 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 IFNl1 and other trophoblast-specific
antiviral factors and/or use alternative strategies to cross the placental barrier.
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