Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain

Abstract

Scientific research on human neural stem cells and cerebral organoids has confirmed the congenital neurotropic and neurodestructive nature of the Zika virus. However, the extent to which prenatal ZIKV infection is associated with more subtle brain alterations, such as epigenetic changes, remains ill defined. Here, we address the question of whether ZIKV infection induces DNA methylation changes with the potential to cause brain disorders later in life.

Use of induced pluripotent stem cells (iPSCs) and cerebral organoids in modeling the congenital infection and neuropathogenesis induced by Zika virus

“…According to the authors, ZIKV could directly trigger the neuropsychiatric and cognitive disease. The results also reinforced the concern that asymptomatic prenatal ZIKV infections could have long‐term effects on neurodevelopment, justifying further rigorous study to identify infected individuals and mechanisms of disease induction …”

“…The authors demonstrated that interferon‐γ efficiently prevented this viral transfer . Findings of another study carried out during the same year predicted that many of the babies with ZIKV infection having anatomic brain abnormalities since birth may have changes in their DNA methylome that could ultimately affect the expression of key genes resulting in a spectrum of neuropsychiatric disorders . According to the authors, ZIKV could directly trigger the neuropsychiatric and cognitive disease.…”

“…26 Findings of another study carried out during the same year predicted that many of the babies with ZIKV infection having anatomic brain abnormalities since birth may have changes in their DNA methylome that could ultimately affect the expression of key genes resulting in a spectrum of neuropsychiatric disorders. 27 According to the authors, ZIKV could directly trigger the neuropsychiatric and cognitive disease. The results also reinforced the concern that asymptomatic prenatal ZIKV infections could have long-term effects on neurodevelopment, justifying further rigorous study to identify infected individuals and mechanisms of disease induction.…”

“…The results also reinforced the concern that asymptomatic prenatal ZIKV infections could have long-term effects on neurodevelopment, justifying further rigorous study to identify infected individuals and mechanisms of disease induction. 27 A vast majority of the published studies were performed on human cells or mice. Two elaborate studies, one by Nowakowski et al, which involved the use of a mouse, ferret, and human 32 the mechanisms of ZIKV pathogenicity and its effects on brain development.…”

Zika virus: Molecular responses and tissue tropism in the mammalian host

“…They reported that ZIKV strains from America and Asia localized initially in deep apical progenitor cells before infecting the cells on the surface of the brain organoid . Brain organoid cultures further revealed that the DNA methylation pattern was altered in neural progenitors and astrocytes, which may subsequently result in brain disorders such as mental retardation and schizophrenia . Infants who do not manifest neurological aberrations at birth may develop psychiatric disorders, neurologic and motor impairments, epilepsy, cognitive anomalies, and long‐term neurodevelopment sequelae, in later years.…”