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

Autor:	Alippe Y; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Wang L; Department of Pathology and Immunology and Center for Genome Sciences, Lab and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA., Coskun R; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine , St. Louis, MO, USA., Muraro SP; Campinas State University, Laboratory of Emerging Viruses , Campinas, Brazil., Zhao FR; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Elam-Noll M; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., White JM; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine , St. Louis, MO, USA., Vota DM; Universidad de Buenos Aires-CONICET, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales , Buenos Aires, Argentina., Hauk VC; Universidad de Buenos Aires-CONICET, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales , Buenos Aires, Argentina., Gordon JI; Department of Pathology and Immunology and Center for Genome Sciences, Lab and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine , St. Louis, MO, USA.; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine , St. Louis, MO, USA., Handley SA; Department of Pathology and Immunology and Center for Genome Sciences, Lab and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA., Diamond MS; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.; Department of Pathology and Immunology and Center for Genome Sciences, Lab and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA.; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.; Andrew M. and Jane M. Bursky the Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine , St. Louis, MO, USA.; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine , St. Louis, MO, USA.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2024 Sep 02; Vol. 221 (9). Date of Electronic Publication: 2024 Jul 23.
DOI:	10.1084/jem.20240694
Abstrakt:	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.)
Databáze:	MEDLINE
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