Abstract
Zika virus (ZIKV) infection during pregnancy in humans results in intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we found that fetus-derived type I interferon (IFN-I) signaling can enhance anti-ZIKV responses and provide clinical benefits to the fetus. Because IFN-λ shares signaling cascades and antiviral functions with IFN-I, we investigated the in vivo effects of IFN-λ in ZIKV-infected pregnant mice. IFN-λ administration during mid-pregnancy reduced ZIKV burden in maternal and fetal organs and alleviated placental injuries and fetal demise. In addition, prophylactic and therapeutic treatment of IFN-λ1 in a human trophoblast line, as well as in primary human amniotic epithelial cells, greatly reduced the ZIKV burden. Our data highlight IFN-λ1 as a potential therapeutic useful for women at risk for congenital Zika disease. Chen et al. find that fetus-derived IFN-I signaling contributes to anti-ZIKV responses. IFN-λ administration during mid-pregnancy promotes host defense and reduces disease severity. IFN-λ1 treatment upregulates MX1 expression and establishes an antiviral state, leading to reduced ZIKV replication or elimination.
Original language | English (US) |
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Pages (from-to) | 1588-1599 |
Number of pages | 12 |
Journal | Cell Reports |
Volume | 21 |
Issue number | 6 |
DOIs | |
State | Published - Nov 7 2017 |
Keywords
- Zika virus
- animal model
- antiviral
- congenital infection
- gestational stage
- human pregnancy
- interferon-λ
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology