Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua.
J Exp Med
; 221(9)2024 09 02.
Article
en En
| MEDLINE
| ID: mdl-39042188
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Placenta
/
Trofoblastos
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Transducción de Señal
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Interferón Tipo I
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Decidua
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Proteínas Adaptadoras Transductoras de Señales
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Receptor de Interferón alfa y beta
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Feto
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Virus Zika
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Infección por el Virus Zika
Idioma:
En
Revista:
J Exp Med
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos