ZIKV Teratogenesis: Clinical Findings in Humans, Mechanisms and Experimental Models

Fabiele B Russo,Fernando R Tocantins,Patricia C B Beltrão-Braga,Giovanna V Souza,Carmen M Toledo

doi:10.3389/fviro.2021.775361

Fabiele B Russo, Fernando R Tocantins + Show 3 more

Open Access

https://doi.org/10.3389/fviro.2021.775361

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Abstract

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) from the Flaviviridae family, first isolated from the Rhesus monkey in 1947 in Uganda. ZIKV is transmitted by mosquito bites, but vertical and sexual transmissions have also been reported. ZIKV infection during pregnancy causes malformation in the developing fetus, especially central nervous system (CNS) damages, with a noticed microcephaly, making ZIKV be recognized as a teratogenic agent and the responsible for congenital Zika syndrome (CZS). However, it is still a short time since CZS was first reported. Consequently, ZIKV pathogenesis is not entirely elucidated, especially considering that affected children are still under neurodevelopment. Here, we will explore the current knowledge about ZIKV teratogenesis focusing on neurological clinical findings in humans, mechanisms, and experimental models used to understand ZIKV pathophysiology.

Highlights

Zika virus (ZIKV) infection is asymptomatic in most cases, the common signs and symptoms are fever, rash, arthralgia, and conjunctival hyperemia [1]
After the outbreak in Brazil, many studies have associated ZIKV with neurological diseases in newborns whose mothers contracted the virus during pregnancy
In microscopic examinations of a fetal brain infected with ZIKV, apoptotic neurons were observed, mainly post-migratory neurons with intermediate differentiation [10]

Summary

Introduction

ZIKV infection is asymptomatic in most cases, the common signs and symptoms are fever, rash, arthralgia, and conjunctival hyperemia [1]. Calcifications and destructive lesions were found, supporting changes in Abbreviations: ATP, adenosine triphosphate; AXL, AXL receptor tyrosine kinase; BAX, Bcl-2-associated protein X; CNS, central nervous system; CSF, cerebrospinal fluid; CZS, congenital Zika syndrome; CNCCs, cranial neural crest cells; CHME3, human microglia cell line; ER, endoplasmic reticulum; ERAD, ER-associated degradation; hESCs, human embryonic stem cells; iPSC, induced pluripotent stem cell; IRF3, Interferon Regulatory Factor 3; LIF, leukemia inhibitory factor; NFκB, nuclear factor kappa B; NPCs, neural progenitor cells; SHANK2, SH3 and multiple ankyrin repeat domains 2; SNARE, soluble NSF attachment receptor; TORCH, toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus, and Herpes; TLR3, toll-like receptor 3; WHO, World Health Organization; VAMP2, Vesicle-Associated Membrane Protein 2; VEGF, vascular endothelial growth factor; UPR, unfolded protein response; ZIKV, Zika virus.

Results

Conclusion