The role of glial cells in Zika virus‐induced neurodegeneration

Abstract

Zika virus (ZIKV) is a strongly neurotropic flavivirus whose infection has been associated with microcephaly in neonates. However, clinical and experimental evidence indicate that ZIKV also affects the adult nervous system. In this regard, in vitro and in vivo studies have shown the ability of ZIKV to infect glial cells. In the central nervous system (CNS), glial cells are represented by astrocytes, microglia, and oligodendrocytes. In contrast, the peripheral nervous system (PNS) constitutes a highly heterogeneous group of cells (Schwann cells, satellite glial cells, and enteric glial cells) spread through the body. These cells are critical in both physiological and pathological conditions; as such, ZIKV-induced glial dysfunctions can be associated with the development and progression of neurological complications, including those related to the adult and aging brain. This review will address the effects of ZIKV infection on CNS and PNS glial cells, focusing on cellular and molecular mechanisms, including changes in the inflammatory response, oxidative stress, mitochondrial dysfunction, Ca 2+ and glutamate homeostasis, neural metabolism, and neuron-glia communication. Of note, preventive and therapeutic strategies that focus on glial cells may emerge to delay and/or prevent the development of ZIKV-induced neurodegeneration and its consequences.André Quincozes-Santos and Larissa Daniele Bobermin contributed equally to this work.

Pathophysiology and mechanisms of hearing impairment related to neonatal infection diseases

“…In vitro findings have also demonstrated that ZIKV can interfere with all stages of neurogenesis (Vouga and Baud, 2016). The alterations caused by ZIKV in the cells of the nervous system are not restricted only to neurons but can also affect glial cells, as was recently discussed in the literature (Quincozes-Santos et al, 2023).…”

Zika virus E protein modulates functions of human brain microvascular endothelial cells and astrocytes: implications on blood-brain barrier properties

“…The attained neurotropic nature of ZIKV makes it capable to infect almost all types of brain cells−microglia, neural progenitor cells and astrocytes; resulting in severe consequences during fetal brain development ( Bhagat et al, 2018 , 2022 ; Quincozes-Santos et al, 2023 ). The associated neurological complications due to vertical transmission (from infected pregnant women to fetus) mainly involves miscarriages, impaired fetal growth or fetuses born with congenital Zika syndrome (CZS) ( van der Linden et al, 2016 ).…”

Kunjin Virus, Zika Virus, and Yellow Fever Virus Infections Have Distinct Effects on the Coding Transcriptome and Proteome of Brain-Derived U87 Cells

“…More specifically, NRG1 has been shown to be expressed in the early stages of brain development [ 33 ], and it would be interesting to investigate the effect of its repression with respect to ZIKV-induced microcephaly [ 34 ]. In addition, since decreased levels of BDNF have been observed in several neurodegenerative diseases [ 32 ], and ZIKV is potentially associated with the development and/or progression of neurodegenerative diseases [ 35 ], it would be interesting to study the role of BDNF repression in this context. Two other attractive candidates for further studies are the genes DLX5 and ATOH8, which are also repressed in ZIKV-infected cells.…”