![]() ![]() Ī number of studies have confirmed that ZIKV selectively infects the NSCs in the fetus. Nevertheless, in some cases it can lead to neurological complications or other adverse reactions, including Guillain–Barré syndrome (GBS). In adult patients, ZIKV infection is usually asymptomatic, with only a low percentage of patients (<20%) reporting mild fever, rash, and joint pain for about 7 days. Despite enormous efforts, the complex mechanisms underlying ZIKV-induced microcephaly and other congenital anomalies in humans have yet to be fully elucidated. Similarly, ZIKV inoculation of rhesus monkeys early in gestation caused alterations of microglial cells and the thinning of the cortical plate in the fetus 3 weeks later. Intraperitoneal administration of ZIKV in pregnant mice led to radial glial cell death in the fetal cerebral cortex area. The causal link between ZIKV infection and neurodevelopment disruption is also supported by animal studies. The most vulnerable time for ZIKV infection is between the first and second trimester of gestation, during which ZIKV impairs neurogenesis by reducing the NSC/NPS pool. Following viral entry into cells, ZIKV disrupts growth and development, causing brain abnormalities. Several additional studies have shown the remarkable tropism of different ZIKV strains for NSCs/NPCs, astrocytes, oligodendrocyte precursor cells, and microglial cells. Indeed, ZIKV proteins and RNA were detected in the amniotic fluids, placental tissues, and brain tissues of fetuses with microcephaly. At that time, ZIKV attracted great attention, due principally to its ability to cross the placental barrier, infect the fetus, and cause severe neurodevelopmental disruptions, including microcephaly. In 2016, an outbreak of ZIKV occurred in the Americas, several Pacific islands, and Southeast Asia, and was followed by the WHO’s declaration of a public health emergency. The transmission occurs through the bite of different species of Aedes mosquitoes. The ZIKV icosahedral capsid contains a positive-sense, single-stranded RNA genome that spans about 10.7 kb. As a member of the Flaviviridae family, ZIKV was first isolated from a rhesus monkey in the Zika forest in Uganda, in 1947. On a quest to find better treatments for GBM, Zika virus (ZIKV) has emerged as a potential anti-tumor therapy. In addition to GSCs, tumor-associated fibroblasts, macrophages/monocytes, and endothelial cells also drive intra-tumor heterogeneity and contribute to drug resistance. Though considerable controversy remains as to which specific cellular mechanisms drive GBM, there is consensus that the GSC population sustains the long-term clonal maintenance of the tumor, and that the divergence of emerging subclones from a common ancestral clone contributes to tumor evolution and recurrence. These cells have been characterized by several groups, and were named glioblastoma stem cells (GSCs), owing to some similarities with normal neural stem/progenitor cells (NSCs/NSPs), including an intrinsic resistance to radiotherapy and chemotherapy treatments. Multipotent, self-renewing, and apoptosis-resistant cells were identified in GBMs about 18 years ago. GBM resistance is attributed mainly to high levels of cellular heterogeneity and tumor plasticity. Current treatments, such as chemotherapy and radiotherapy, are ineffective in the majority of patients, who ultimately will suffer multiple relapses. Glioblastoma (GBM), or grade IV glioma, according to the World Health Organization (WHO) classification, is the most malignant tumor occurring in the human central nervous system (CNS), with a median overall survival rate in the United States of about 8 months. Tumors are one of the leading causes of death worldwide. While preliminary data support ZIKV tropism toward GSCs, a more accurate study of ZIKV mechanisms of action is fundamental in order to launch ZIKV-based clinical trials for GBM patients. This finding has led various groups to evaluate ZIKV’s effects against glioblastoma stem cells (GSCs), supposedly responsible for GBM onset, progression, and therapy resistance. ZIKV is an arbovirus of the Flaviviridae family, and its infection during development has been associated with central nervous system (CNS) malformations, including microcephaly, through the targeting of neural stem/progenitor cells (NSCs/NPCs). ![]() The recent discovery that Zika virus (ZIKV) has an oncolytic action against GBM has brought hope for the development of new therapeutic approaches. In the majority of cases, the tumor recurs within 32–36 weeks of initial treatment. At present, no chemotherapy or radiotherapy regimen is associated with a positive long-term outcome. Glioblastoma (GBM) is the most aggressive among the neurological tumors. ![]()
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