Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua.
Yael AlippeLeran WangReyan CoskunStefanie Primon MuraroFang R ZhaoMichelle Elam-NollJ Michael WhiteDaiana M VotaVanesa C HaukJeffrey I GordonScott A HandleyMichael S. DiamondPublished in: The Journal of experimental medicine (2024)
The contribution of placental immune responses to congenital Zika virus (ZIKV) syndrome remains poorly understood. Here, we leveraged a mouse model of ZIKV infection to identify mechanisms of innate immune restriction exclusively in the fetal compartment of the placenta. ZIKV principally infected mononuclear trophoblasts in the junctional zone, which was limited by mitochondrial antiviral-signaling protein (MAVS) and type I interferon (IFN) signaling mechanisms. Single nuclear RNA sequencing revealed MAVS-dependent expression of IFN-stimulated genes (ISGs) in spongiotrophoblasts but not in other placental cells that use alternate pathways to induce ISGs. ZIKV infection of Ifnar1-/- or Mavs-/- placentas was associated with greater infection of the adjacent immunocompetent decidua, and heterozygous Mavs+/- or Ifnar1+/- dams carrying immunodeficient fetuses sustained greater maternal viremia and tissue infection than dams carrying wild-type fetuses. Thus, MAVS-IFN signaling in the fetus restricts ZIKV infection in junctional zone trophoblasts, which modulates dissemination and outcome for both the fetus and the pregnant mother.
Keyphrases
- zika virus
- immune response
- dengue virus
- dendritic cells
- mouse model
- aedes aegypti
- pregnant women
- poor prognosis
- physical activity
- body mass index
- single cell
- transcription factor
- toll like receptor
- epithelial mesenchymal transition
- long non coding rna
- peripheral blood
- wild type
- dna methylation
- genome wide
- cell death
- cell cycle arrest