Reactive Oxygen Species (ROS) Are Not a Key Determinant for Zika Virus-Induced Apoptosis in SH-SY5Y Neuroblastoma Cells.

Leila Rodrigues De Mendonça-Vieira,Nágela Ghabdan Zanluqui,Elisa De Almeida Neves Azevedo,Armando Menezes-Neto,Jean Pierre Schatzmann Peron,Conceição Elidianne Aníbal-Silva,Rafael Freitas De Oliveira Franca

doi:10.3390/v13112111

Leila Rodrigues De Mendonça-Vieira, Nágela Ghabdan Zanluqui + Show 5 more

Open Access

https://doi.org/10.3390/v13112111

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Journal: Viruses	Publication Date: Oct 20, 2021
Citations: 9	License type: CC BY 4.0

Affiliation: Fundação Oswaldo Cruz, Universidade de São Paulo

Abstract

Introduction: ZIKV is a highly neurotropic virus that can cause the death of infected neuroprogenitor cells through mitochondrial damage and intrinsic apoptotic signaling. In this context, the role of reactive oxygen species (ROS) in neuronal cell death caused by ZIKV still remains elusive. Objective: We aimed at evaluating the role of these cellular components in the death of human undifferentiated neuroblastoma cell line infected with ZIKV. Results: ZIKV infection resulted in the extensive death of SH-SY5Y cells with the upregulation of several genes involved in survival and apoptotic responses as well as the colocalization of mitochondrial staining with ZIKV Envelope (E) protein. Notably, levels of intracellular reactive oxygen species (ROS) were not altered during ZIKV infection in undifferentiated SH-SY5Y cells, and consistent with these results, the treatment of infected cells with the widely studied ROS scavenger N-acetylcysteine (NAC) did not prevent cell death in these cells. Conclusion: Altogether, our results suggest that excessive ROS production is not the main trigger of SH-SY5Y cells death in ZIKV infection.

Highlights

The emergence of Zika Virus (ZIKV) in Latin America was followed by a major economic and social impact, mainly for pregnant women and for the families of children affected by Congenital Zika Syndrome [1]
Mock- and ZIKV-infected (MOI 5) SH-SY5Y cells (1 × 105 ) grown in 0.13 mm round glass slides were processed at 2 dpi for mitochondrial staining using a MitotrackerTM Deep
We demonstrate that a contemporary South American strain of ZIKV is able to infect human undifferentiated SH-SY5Y cells, resulting in extensive cell death, mainly through the engagement of intrinsic apoptosis, further corroborating previous evidence [10]

Summary

Introduction

The emergence of Zika Virus (ZIKV) in Latin America was followed by a major economic and social impact, mainly for pregnant women and for the families of children affected by Congenital Zika Syndrome [1]. As a highly neurotropic virus, ZIKV is able to infect the neural progenitor cells of unborn children and interferes with several key cellular processes, such as cell cycle [2], neuronal differentiation [3], and neuronal migration [4]. The loss of these important cellular functions induces premature neuronal death in the forming. A previous report showed that the mitochondrial damage and activation of intrinsic apoptotic pathways are triggered by ZIKV infection in neuroprogenitor cells [2]

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