Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys

Abstract The absence of an adequate animal model for studies has limited the understanding of congenital Zika syndrome (CZS) in humans during the outbreak in America. In this study, we used squirrel monkeys (Saimiri collinsi), a neotropical primate (which mimics the stages of human pregnancy), as a...

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Autores principales: Bianca Nascimento de Alcantara, Aline Amaral Imbeloni, Darlene de Brito Simith Durans, Marialva Tereza Ferreira de Araújo, Ermelinda do Rosário Moutinho da Cruz, Carlos Alberto Marques de Carvalho, Maria Helena Rodrigues de Mendonça, Jorge Rodrigues de Sousa, Adriana Freitas Moraes, Arnaldo Jorge Martins Filho, Maria de Lourdes Gomes Lima, Orlando Pereira Amador Neto, Jannifer Oliveira Chiang, Sarah Raphaella Rocha de Azevedo Scalercio, Liliane Almeida Carneiro, Juarez Antônio Simões Quaresma, Pedro Fernando da Costa Vasconcelos, Daniele Barbosa de Almeida Medeiros
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/f2a7830ab3a446f089e345a8515145e1
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spelling oai:doaj.org-article:f2a7830ab3a446f089e345a8515145e12021-12-02T11:39:20ZHistopathological lesions of congenital Zika syndrome in newborn squirrel monkeys10.1038/s41598-021-85571-12045-2322https://doaj.org/article/f2a7830ab3a446f089e345a8515145e12021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85571-1https://doaj.org/toc/2045-2322Abstract The absence of an adequate animal model for studies has limited the understanding of congenital Zika syndrome (CZS) in humans during the outbreak in America. In this study, we used squirrel monkeys (Saimiri collinsi), a neotropical primate (which mimics the stages of human pregnancy), as a model of Zika virus (ZIKV) infection. Seven pregnant female squirrel monkeys were experimentally infected at three different gestational stages, and we were able reproduce a broad range of clinical manifestations of ZIKV lesions observed in newborn humans. Histopathological and immunohistochemical analyses of early-infected newborns (2/4) revealed damage to various areas of the brain and ZIKV antigens in the cytoplasm of neurons and glial cells, indicative of CZS. The changes caused by ZIKV infection were intrauterine developmental delay, ventriculomegaly, simplified brain gyri, vascular impairment and neuroprogenitor cell dysfunction. Our data show that the ZIKV infection outcome in squirrel monkeys is similar to that in humans, indicating that this model can be used to help answer questions about the effect of ZIKV infection on neuroembryonic development and the morphological changes induced by CZS.Bianca Nascimento de AlcantaraAline Amaral ImbeloniDarlene de Brito Simith DuransMarialva Tereza Ferreira de AraújoErmelinda do Rosário Moutinho da CruzCarlos Alberto Marques de CarvalhoMaria Helena Rodrigues de MendonçaJorge Rodrigues de SousaAdriana Freitas MoraesArnaldo Jorge Martins FilhoMaria de Lourdes Gomes LimaOrlando Pereira Amador NetoJannifer Oliveira ChiangSarah Raphaella Rocha de Azevedo ScalercioLiliane Almeida CarneiroJuarez Antônio Simões QuaresmaPedro Fernando da Costa VasconcelosDaniele Barbosa de Almeida MedeirosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Bianca Nascimento de Alcantara
Aline Amaral Imbeloni
Darlene de Brito Simith Durans
Marialva Tereza Ferreira de Araújo
Ermelinda do Rosário Moutinho da Cruz
Carlos Alberto Marques de Carvalho
Maria Helena Rodrigues de Mendonça
Jorge Rodrigues de Sousa
Adriana Freitas Moraes
Arnaldo Jorge Martins Filho
Maria de Lourdes Gomes Lima
Orlando Pereira Amador Neto
Jannifer Oliveira Chiang
Sarah Raphaella Rocha de Azevedo Scalercio
Liliane Almeida Carneiro
Juarez Antônio Simões Quaresma
Pedro Fernando da Costa Vasconcelos
Daniele Barbosa de Almeida Medeiros
Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys
description Abstract The absence of an adequate animal model for studies has limited the understanding of congenital Zika syndrome (CZS) in humans during the outbreak in America. In this study, we used squirrel monkeys (Saimiri collinsi), a neotropical primate (which mimics the stages of human pregnancy), as a model of Zika virus (ZIKV) infection. Seven pregnant female squirrel monkeys were experimentally infected at three different gestational stages, and we were able reproduce a broad range of clinical manifestations of ZIKV lesions observed in newborn humans. Histopathological and immunohistochemical analyses of early-infected newborns (2/4) revealed damage to various areas of the brain and ZIKV antigens in the cytoplasm of neurons and glial cells, indicative of CZS. The changes caused by ZIKV infection were intrauterine developmental delay, ventriculomegaly, simplified brain gyri, vascular impairment and neuroprogenitor cell dysfunction. Our data show that the ZIKV infection outcome in squirrel monkeys is similar to that in humans, indicating that this model can be used to help answer questions about the effect of ZIKV infection on neuroembryonic development and the morphological changes induced by CZS.
format article
author Bianca Nascimento de Alcantara
Aline Amaral Imbeloni
Darlene de Brito Simith Durans
Marialva Tereza Ferreira de Araújo
Ermelinda do Rosário Moutinho da Cruz
Carlos Alberto Marques de Carvalho
Maria Helena Rodrigues de Mendonça
Jorge Rodrigues de Sousa
Adriana Freitas Moraes
Arnaldo Jorge Martins Filho
Maria de Lourdes Gomes Lima
Orlando Pereira Amador Neto
Jannifer Oliveira Chiang
Sarah Raphaella Rocha de Azevedo Scalercio
Liliane Almeida Carneiro
Juarez Antônio Simões Quaresma
Pedro Fernando da Costa Vasconcelos
Daniele Barbosa de Almeida Medeiros
author_facet Bianca Nascimento de Alcantara
Aline Amaral Imbeloni
Darlene de Brito Simith Durans
Marialva Tereza Ferreira de Araújo
Ermelinda do Rosário Moutinho da Cruz
Carlos Alberto Marques de Carvalho
Maria Helena Rodrigues de Mendonça
Jorge Rodrigues de Sousa
Adriana Freitas Moraes
Arnaldo Jorge Martins Filho
Maria de Lourdes Gomes Lima
Orlando Pereira Amador Neto
Jannifer Oliveira Chiang
Sarah Raphaella Rocha de Azevedo Scalercio
Liliane Almeida Carneiro
Juarez Antônio Simões Quaresma
Pedro Fernando da Costa Vasconcelos
Daniele Barbosa de Almeida Medeiros
author_sort Bianca Nascimento de Alcantara
title Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys
title_short Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys
title_full Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys
title_fullStr Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys
title_full_unstemmed Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys
title_sort histopathological lesions of congenital zika syndrome in newborn squirrel monkeys
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/f2a7830ab3a446f089e345a8515145e1
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