Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon Action

Jinling Chen, Yuejin Liang, Panpan Yi, Lanman Xu, Hal K. Hawkins, Shannan L. Rossi, Lynn Soong, Jiyang Cai, Ramkumar Menon, Jiaren Sun

Research output: Contribution to journalArticle

42 Scopus citations

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 languageEnglish (US)
Pages (from-to)1588-1599
Number of pages12
JournalCell Reports
Volume21
Issue number6
DOIs
StatePublished - Nov 7 2017

Keywords

  • Zika virus
  • animal model
  • antiviral
  • congenital infection
  • gestational stage
  • human pregnancy
  • interferon-λ

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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