Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain

ABSTRACT Zika virus (ZIKV) infection during early pregnancy can cause microcephaly and associated defects at birth, but whether it can induce neurologic sequelae that appear later in life remains unclear. Using a model of the developing brain based on embryonic stem cell-derived brain organoids, we...

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Autores principales:	Sylvie Janssens, Michael Schotsaert, Rahul Karnik, Vinod Balasubramaniam, Marion Dejosez, Alexander Meissner, Adolfo García-Sastre, Thomas P. Zwaka
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	DNA methylation Zika virus astrocytes brain disorders microcephaly neurons Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/18b89b62e6234d09b23dad5a2bc95161
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spelling	oai:doaj.org-article:18b89b62e6234d09b23dad5a2bc951612021-12-02T18:39:46ZZika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain10.1128/mSystems.00219-172379-5077https://doaj.org/article/18b89b62e6234d09b23dad5a2bc951612018-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00219-17https://doaj.org/toc/2379-5077ABSTRACT Zika virus (ZIKV) infection during early pregnancy can cause microcephaly and associated defects at birth, but whether it can induce neurologic sequelae that appear later in life remains unclear. Using a model of the developing brain based on embryonic stem cell-derived brain organoids, we studied the impact of ZIKV infection on the DNA methylation pattern across the entire genome in selected neural cell types. The virus unexpectedly alters the DNA methylome of neural progenitors, astrocytes, and differentiated neurons at genes that have been implicated in the pathogenesis of a number of brain disorders, most prominently mental retardation and schizophrenia. Our results suggest that ZIKV infection during fetal development could lead to a spectrum of delayed-onset neuropsychiatric complications. IMPORTANCE Scientific research on human neural stem cells and cerebral organoids has confirmed the congenital neurotropic and neurodestructive nature of the Zika virus. However, the extent to which prenatal ZIKV infection is associated with more subtle brain alterations, such as epigenetic changes, remains ill defined. Here, we address the question of whether ZIKV infection induces DNA methylation changes with the potential to cause brain disorders later in life.Sylvie JanssensMichael SchotsaertRahul KarnikVinod BalasubramaniamMarion DejosezAlexander MeissnerAdolfo García-SastreThomas P. ZwakaAmerican Society for MicrobiologyarticleDNA methylationZika virusastrocytesbrain disordersmicrocephalyneuronsMicrobiologyQR1-502ENmSystems, Vol 3, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNA methylation Zika virus astrocytes brain disorders microcephaly neurons Microbiology QR1-502
spellingShingle	DNA methylation Zika virus astrocytes brain disorders microcephaly neurons Microbiology QR1-502 Sylvie Janssens Michael Schotsaert Rahul Karnik Vinod Balasubramaniam Marion Dejosez Alexander Meissner Adolfo García-Sastre Thomas P. Zwaka Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain
description	ABSTRACT Zika virus (ZIKV) infection during early pregnancy can cause microcephaly and associated defects at birth, but whether it can induce neurologic sequelae that appear later in life remains unclear. Using a model of the developing brain based on embryonic stem cell-derived brain organoids, we studied the impact of ZIKV infection on the DNA methylation pattern across the entire genome in selected neural cell types. The virus unexpectedly alters the DNA methylome of neural progenitors, astrocytes, and differentiated neurons at genes that have been implicated in the pathogenesis of a number of brain disorders, most prominently mental retardation and schizophrenia. Our results suggest that ZIKV infection during fetal development could lead to a spectrum of delayed-onset neuropsychiatric complications. IMPORTANCE Scientific research on human neural stem cells and cerebral organoids has confirmed the congenital neurotropic and neurodestructive nature of the Zika virus. However, the extent to which prenatal ZIKV infection is associated with more subtle brain alterations, such as epigenetic changes, remains ill defined. Here, we address the question of whether ZIKV infection induces DNA methylation changes with the potential to cause brain disorders later in life.
format	article
author	Sylvie Janssens Michael Schotsaert Rahul Karnik Vinod Balasubramaniam Marion Dejosez Alexander Meissner Adolfo García-Sastre Thomas P. Zwaka
author_facet	Sylvie Janssens Michael Schotsaert Rahul Karnik Vinod Balasubramaniam Marion Dejosez Alexander Meissner Adolfo García-Sastre Thomas P. Zwaka
author_sort	Sylvie Janssens
title	Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain
title_short	Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain
title_full	Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain
title_fullStr	Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain
title_full_unstemmed	Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain
title_sort	zika virus alters dna methylation of neural genes in an organoid model of the developing human brain
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/18b89b62e6234d09b23dad5a2bc95161
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Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain

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