Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua

Autores
Alippe, Yael; Wang, Leran; Coskun, Reyan; Muraro, Stéfanie P.; Zhao, Fang R.; Elam Noll, Michelle; White, J. Michael; Vota, Daiana Marina; Hauk, Vanesa Cintia; Gordon, Jeffrey I.; Handley, Scott A.; Diamond, Michael S.
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Alippe, Yael. University of Washington. School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wang, Leran. University of Washington. School of Medicine; Estados Unidos
Fil: Coskun, Reyan. University of Washington. School of Medicine; Estados Unidos
Fil: Muraro, Stéfanie P.. Universidade Estadual de Campinas; Brasil
Fil: Zhao, Fang R.. University of Washington. School of Medicine; Estados Unidos
Fil: Elam Noll, Michelle. University of Washington. School of Medicine; Estados Unidos
Fil: White, J. Michael. University of Washington. School of Medicine; Estados Unidos
Fil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Hauk, Vanesa Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Gordon, Jeffrey I.. University of Washington. School of Medicine; Estados Unidos
Fil: Handley, Scott A.. University of Washington. School of Medicine; Estados Unidos
Fil: Diamond, Michael S.. University of Washington. School of Medicine; Estados Unidos
Materia
ZIKV
PLACENTA
DECIDUA
FETAL GROWTH
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266810
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/266810
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal deciduaAlippe, YaelWang, LeranCoskun, ReyanMuraro, Stéfanie P.Zhao, Fang R.Elam Noll, MichelleWhite, J. MichaelVota, Daiana MarinaHauk, Vanesa CintiaGordon, Jeffrey I.Handley, Scott A.Diamond, Michael S.ZIKVPLACENTADECIDUAFETAL GROWTHhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The 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.Fil: Alippe, Yael. University of Washington. School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wang, Leran. University of Washington. School of Medicine; Estados UnidosFil: Coskun, Reyan. University of Washington. School of Medicine; Estados UnidosFil: Muraro, Stéfanie P.. Universidade Estadual de Campinas; BrasilFil: Zhao, Fang R.. University of Washington. School of Medicine; Estados UnidosFil: Elam Noll, Michelle. University of Washington. School of Medicine; Estados UnidosFil: White, J. Michael. University of Washington. School of Medicine; Estados UnidosFil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Hauk, Vanesa Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Gordon, Jeffrey I.. University of Washington. School of Medicine; Estados UnidosFil: Handley, Scott A.. University of Washington. School of Medicine; Estados UnidosFil: Diamond, Michael S.. University of Washington. School of Medicine; Estados UnidosRockefeller University Press2024-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266810Alippe, Yael; Wang, Leran; Coskun, Reyan; Muraro, Stéfanie P.; Zhao, Fang R.; et al.; Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua; Rockefeller University Press; Journal of Experimental Medicine; 221; 9; 9-2024; 1-260022-1007CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://rupress.org/jem/article/221/9/e20240694/276872/Fetal-MAVS-and-type-I-IFN-signaling-pathwaysinfo:eu-repo/semantics/altIdentifier/doi/10.1084/jem.20240694info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:32:48Zoai:ri.conicet.gov.ar:11336/266810instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:32:48.38CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua
title Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua
spellingShingle Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua
Alippe, Yael
ZIKV
PLACENTA
DECIDUA
FETAL GROWTH
title_short Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua
title_full Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua
title_fullStr Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua
title_full_unstemmed Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua
title_sort Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua
dc.creator.none.fl_str_mv Alippe, Yael
Wang, Leran
Coskun, Reyan
Muraro, Stéfanie P.
Zhao, Fang R.
Elam Noll, Michelle
White, J. Michael
Vota, Daiana Marina
Hauk, Vanesa Cintia
Gordon, Jeffrey I.
Handley, Scott A.
Diamond, Michael S.
author Alippe, Yael
author_facet Alippe, Yael
Wang, Leran
Coskun, Reyan
Muraro, Stéfanie P.
Zhao, Fang R.
Elam Noll, Michelle
White, J. Michael
Vota, Daiana Marina
Hauk, Vanesa Cintia
Gordon, Jeffrey I.
Handley, Scott A.
Diamond, Michael S.
author_role author
author2 Wang, Leran
Coskun, Reyan
Muraro, Stéfanie P.
Zhao, Fang R.
Elam Noll, Michelle
White, J. Michael
Vota, Daiana Marina
Hauk, Vanesa Cintia
Gordon, Jeffrey I.
Handley, Scott A.
Diamond, Michael S.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ZIKV
PLACENTA
DECIDUA
FETAL GROWTH
topic ZIKV
PLACENTA
DECIDUA
FETAL GROWTH
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Alippe, Yael. University of Washington. School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wang, Leran. University of Washington. School of Medicine; Estados Unidos
Fil: Coskun, Reyan. University of Washington. School of Medicine; Estados Unidos
Fil: Muraro, Stéfanie P.. Universidade Estadual de Campinas; Brasil
Fil: Zhao, Fang R.. University of Washington. School of Medicine; Estados Unidos
Fil: Elam Noll, Michelle. University of Washington. School of Medicine; Estados Unidos
Fil: White, J. Michael. University of Washington. School of Medicine; Estados Unidos
Fil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Hauk, Vanesa Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Gordon, Jeffrey I.. University of Washington. School of Medicine; Estados Unidos
Fil: Handley, Scott A.. University of Washington. School of Medicine; Estados Unidos
Fil: Diamond, Michael S.. University of Washington. School of Medicine; Estados Unidos
description 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.
publishDate 2024
dc.date.none.fl_str_mv 2024-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/266810
Alippe, Yael; Wang, Leran; Coskun, Reyan; Muraro, Stéfanie P.; Zhao, Fang R.; et al.; Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua; Rockefeller University Press; Journal of Experimental Medicine; 221; 9; 9-2024; 1-26
0022-1007
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266810
identifier_str_mv Alippe, Yael; Wang, Leran; Coskun, Reyan; Muraro, Stéfanie P.; Zhao, Fang R.; et al.; Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua; Rockefeller University Press; Journal of Experimental Medicine; 221; 9; 9-2024; 1-26
0022-1007
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://rupress.org/jem/article/221/9/e20240694/276872/Fetal-MAVS-and-type-I-IFN-signaling-pathways
info:eu-repo/semantics/altIdentifier/doi/10.1084/jem.20240694
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Rockefeller University Press
publisher.none.fl_str_mv Rockefeller University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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