Dados do Trabalho

Título

Zika Virus: a study on the effects of the antibodies in murine microglial cell lineage

Introdução

Zika virus (ZIKV) infection in pregnant women is associated with severe damage to the central nervous system of the fetus, such as the Congenital Zika Syndrome. Due to its transplacental transmission, ZIKV produces irreversible lesions in the fetus, by inducing neuroinflammation, microglial activation and secretion of neurotoxic factors, that can compromise brain development. Despite of the limited understanding about its pathophysiology, it is known that the fetus presents insufficient humoral immune response, and its protection may be provided by maternal antibodies. This protection, however, is still controversial and there is evidence suggesting harmful effects instead.

Objetivo

In this context, it is necessary to elucidate the neuropathogenic effects of ZIKV and the neuroimmune mechanisms involved in this pathology. The present work aim to evaluate the role of the ZIKV+IgG+ complex in murine microglia cells (BV2), in order to investigate its influence on the viability of these cells, as well as their involvement in oxidative stress and mitochondrial membrane potential.

Método

For this purpose, BV2 were exposed for 24 or 72 hours, to ZIKV, ZIKA-IgG+ antibody or ZIKV+IgG+ complex. Effects of exposure to treatments were evaluated by the cell viability assay (MTT). Oxidative stress was assessed by oxidation of DCFHDA and mitochondrial membrane potential was measured using the JC-1 fluorescence assay. Gene expression of ZIKV and STX1-A, which is involved in inflammation, was evaluated by RT-PCR.

Resultados

It was observed that ZIKV-IgG+ antibodies, alone and the ZIKV+IgG+ complex, are cytotoxic to microglia, impairing the viability of these cells, altering mitochondrial membrane potential and inducing ROS production, especially in long-term exposure. Hence, the activation and the interference in the production of a neurotoxic environment by these antibodies may be a result of oxidative stress and a negative intervention in the mitochondrial membrane potential. Regarding the gene expression, a reduction of STX1-A relative expression was observed in the groups exposed by ZIKV in the 24h exposure. No modifications and an increase of STX1-A expression were detected in the antibodies group in the 24h and 72h exposures, respectively.

Conclusão

In conclusion, ZIKV-IgG+ antibodies are harmful to microglia and these mechanisms may be related to the potential for ZIKV neuroinflammation, and, consequently, to the severe long-term damage in the central nervous system.

Palavras-chave

Zika virus; Microglia; Cell viability; Oxidative stress; Mitochondrial homeostasis.

Área

Neurociência básica