Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys

Bianca Nascimento De Alcantara,Pedro Fernando Da Costa Vasconcelos,Jorge Rodrigues De Sousa,Sarah Raphaella Rocha De Azevedo Scalercio,Aline Amaral Imbeloni,Arnaldo Jorge Martins Filho,Jannifer Oliveira Chiang,Ermelinda Do Rosário Moutinho Da Cruz,Orlando Pereira Amador Neto,Liliane Almeida Carneiro,Carlos Alberto Marques De Carvalho,Adriana Freitas Moraes,Maria Helena Rodrigues De Mendonça,Juarez Antônio Simões Quaresma,Maria De Lourdes Gomes Lima,Daniele Barbosa De Almeida Medeiros,Marialva Tereza Ferreira De Araújo,Darlene De Brito Simith Durans

doi:10.1038/s41598-021-85571-1

Bianca Nascimento De Alcantara, Pedro Fernando Da Costa Vasconcelos + Show 16 more

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https://doi.org/10.1038/s41598-021-85571-1

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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.

Highlights

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
We investigated the possibility that the Asian strain of Zika virus (ZIKV) circulating in Brazil could cause CZS-type injuries in newborn squirrel monkeys (Saimiri collinsi) whose mothers were infected at different stages of
Macroscopic (Fig. 2) and microscopic (Fig. 3) changes in the central nervous system (CNS) were observed in the offspring of females infected at different gestational periods and compared with those in the CNS of the newborns in the negative control group (G4) (Fig. 2A), as well as with the information available on the lesions described in humans newborns

Summary

Introduction

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. We used squirrel monkeys (Saimiri collinsi), a neotropical primate (which mimics the stages of human pregnancy), as a model of Zika virus (ZIKV) infection. ZIKV was first isolated in Uganda in 1947, and since the virus has been detected in Africa and later in Asia, causing outbreaks of a dengue-like febrile illness[2]. In 2016, at the beginning of the outbreak, histopathological descriptions associated with congenital Zika syndrome (CZS) in humans were scarce due to ethical issues, which limited histopathological studies[8,10,11,12]. Neotropical primates belonging to the Saimiri genus have been used as a model for many infectious diseases, especially in studies on viral e ncephalitis[20,21,22]

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