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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 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.

SUBMITTER: de Alcantara BN

PROVIDER: S-EPMC7971060 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys.

de Alcantara Bianca Nascimento BN Imbeloni Aline Amaral AA de Brito Simith Durans Darlene D de Araújo Marialva Tereza Ferreira MTF do Rosário Moutinho da Cruz Ermelinda E de Carvalho Carlos Alberto Marques CAM de Mendonça Maria Helena Rodrigues MHR de Sousa Jorge Rodrigues JR Moraes Adriana Freitas AF Filho Arnaldo Jorge Martins AJM de Lourdes Gomes Lima Maria M Neto Orlando Pereira Amador OPA Chiang Jannifer Oliveira JO de Azevedo Scalercio Sarah Raphaella Rocha SRR Carneiro Liliane Almeida LA Quaresma Juarez Antônio Simões JAS da Costa Vasconcelos Pedro Fernando PF de Almeida Medeiros Daniele Barbosa DB

Scientific reports 20210317 1

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 manifestati ...[more]

PMID: 33731800

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Project description:BackgroundChildren with in utero Zika virus (ZIKV) exposure without congenital Zika syndrome (CZS) are at risk for abnormal neurodevelopment. Preschool-age outcomes for children with antenatal ZIKV exposure have not yet been established.MethodsChildren with in utero ZIKV exposure and non-exposed controls had neurodevelopmental evaluations at age 3-5 years in Sabanalarga, Colombia. Cases did not have CZS and were previously evaluated prenatally through age 18 months. Controls were born before ZIKV arrival to Colombia. Neurodevelopmental assessments included Pediatric Evaluation of Disability Inventory (PEDI-CAT), Behavior Rating Inventory of Executive Function (BRIEF-P), Bracken School Readiness Assessment (BSRA), and Movement Assessment Battery for Children (MABC). Family demographics and child medical history were recorded.ResultsFifty-five ZIKV-exposed children were evaluated at mean age 3.6 years and 70 controls were evaluated at 5.2 years. Family demographics were similar between groups. BRIEF-P t-scores were higher for cases than controls in shift and flexibility domains. Cases had lower PEDI-CAT mobility t-scores compared to controls. There was no difference in MABC between groups. In 11% of cases and 1% of controls, parents reported child mood problems.ConclusionsChildren with in utero ZIKV exposure without CZS may demonstrate emerging differences in executive function, mood, and adaptive mobility that require continued evaluation.ImpactPreschool neurodevelopmental outcome in children with in utero Zika virus exposure is not yet known, since the Zika virus epidemic occurred in 2015-2017 and these children are only now entering school age. This study finds that Colombian children with in utero Zika virus exposure without congenital Zika syndrome are overall developing well but may have emerging differences in executive function, behavior and mood, and adaptive mobility compared to children without in utero Zika virus exposure. Children with in utero Zika virus exposure require continued multi-domain longitudinal neurodevelopmental evaluation through school age.

Dataset Information

Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys.

Publications

Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys.

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