1. Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua.
- Author
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Alippe Y, Wang L, Coskun R, Muraro SP, Zhao FR, Elam-Noll M, White JM, Vota DM, Hauk VC, Gordon JI, Handley SA, and Diamond MS
- Subjects
- Female, Animals, Pregnancy, Mice, Mice, Inbred C57BL, Mice, Knockout, Immunity, Innate, Pregnancy Complications, Infectious immunology, Pregnancy Complications, Infectious virology, Disease Models, Animal, Interferon Type I metabolism, Interferon Type I immunology, Signal Transduction immunology, Adaptor Proteins, Signal Transducing metabolism, Adaptor Proteins, Signal Transducing genetics, Placenta immunology, Placenta virology, Placenta metabolism, Zika Virus Infection immunology, Zika Virus Infection virology, Zika Virus immunology, Zika Virus physiology, Decidua immunology, Decidua virology, Decidua metabolism, Fetus immunology, Fetus virology, Trophoblasts immunology, Trophoblasts virology, Trophoblasts metabolism, Receptor, Interferon alpha-beta genetics, Receptor, Interferon alpha-beta metabolism
- Abstract
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., (© 2024 Alippe et al.)
- Published
- 2024
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