Interleukin-27 is antiviral against Zika virus at the maternal-fetal interface

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Abstract
Congenital viral infections can have severe consequences for pregnancy and fetal outcomes. Remarkably, the fetal-derived placenta serves as a robust barrier to infection through meticulous regulation by immune effectors and cytokines. Yet, the regulatory roles of many cytokines remain undefined at the maternal-fetal interface, including Interleukin-27 (IL-27). Here, we show that trophoblast organoids derived from human placentas constitutively express both IL-27 and its receptor, and restrict Zika virus infection through IL-27 signaling. Through bulk RNA-sequencing of trophoblast organoids in the absence and presence of IL-27 signaling, we demonstrate IL-27-mediated upregulation of antiviral genes. Finally, we show that IL-27 signaling is critical to restricting placental viral burdens and protecting against pathologic fetal outcomes during murine congenital Zika virus infection. In this work, we demonstrate a novel role for IL-27 in the placenta and establish IL-27 as an innate antiviral defense at the maternal-fetal interface during congenital viral infection.
Funding Information
  • U.S. Department of Health & Human Services | National Institutes of Health (1R01AI180138-01)
  • Pew Charitable Trusts (Biomedical Scholars Program)
  • Penn | Perelman School of Medicine, University of Pennsylvania (Linda Pechenik Montague Investigator Award)

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