Zika virus induces astrocyte differentiation in neural stem cells

Lossia, Olivia V.; Conway, Michael J.; Tree, Maya O.; Williams, R. J. P.; Goldthorpe, Stacy C.; Srinageshwar, Bhairavi; Rossignol, Julien

doi:10.1007/s13365-017-0589-x

Cited by 23 publications

(23 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, numerous biological studies have now associated ZIKV infection with microcephaly and prenatal lethality in animal models [ 7 , 8 , 9 , 10 , 11 , 12 ]. These and other studies of ZIKV infection in the developing brain of murine models demonstrate the deleterious effects of infection upon neuronal and glia populations [ 7 , 10 , 13 , 14 , 15 , 16 , 17 , 18 ]. In particular, it is now clear that ZIKV infects embryonic neural progenitor cells, resulting in apoptosis and microcephaly [ 10 , 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 62%

A Fluorescent Cell-Based System for Imaging Zika Virus Infection in Real-Time

McFadden

Mitchell-Dick

Vazquez

et al. 2018

Viruses

View full text Add to dashboard Cite

Zika virus (ZIKV) is a re-emerging flavivirus that is transmitted to humans through the bite of an infected mosquito or through sexual contact with an infected partner. ZIKV infection during pregnancy has been associated with numerous fetal abnormalities, including prenatal lethality and microcephaly. However, until recent outbreaks in the Americas, ZIKV has been relatively understudied, and therefore the biology and pathogenesis of ZIKV infection remain incompletely understood. Better methods to study ZIKV infection in live cells could enhance our understanding of the biology of ZIKV and the mechanisms by which ZIKV contributes to fetal abnormalities. To this end, we developed a fluorescent cell-based reporter system allowing for live imaging of ZIKV-infected cells. This system utilizes the protease activity of the ZIKV non-structural proteins 2B and 3 (NS2B-NS3) to specifically mark virus-infected cells. Here, we demonstrate the utility of this fluorescent reporter for identifying cells infected by ZIKV strains of two lineages. Further, we use this system to determine that apoptosis is induced in cells directly infected with ZIKV in a cell-autonomous manner. Ultimately, approaches that can directly track ZIKV-infected cells at the single cell-level have the potential to yield new insights into the host-pathogen interactions that regulate ZIKV infection and pathogenesis.

show abstract

Section: Introductionmentioning

confidence: 62%

A Fluorescent Cell-Based System for Imaging Zika Virus Infection in Real-Time

McFadden

Mitchell-Dick

Vazquez

et al. 2018

Viruses

View full text Add to dashboard Cite

show abstract

“…In addition to affecting genes involved in the cell cycle, ZIKV infection has been shown to significantly downregulate expression of genes associated with neural stem cells, neuronal cell types, and oligodendrocytes. As well as this downregulation, infection has been shown to upregulate certain genes, for example those associated with astrocyte differentiation as well as antiviral genes such as Toll-Like Receptor 3 (TLR3), Viperin and CCL2 [75]. This data suggests that, during infection, ZIKV targets several neural cell types, while also inducing differentiation of astrocytes and promoting TLR3 in order to initiate cellular disorder.…”

Section: Initial Infectionmentioning

confidence: 99%

“…Some studies have reported that the early cellular targets of the virus appear to be astrocytes [75,113]. Astrocytes are some of the first responders to viral infections.…”

Section: Initial Cellular Targetsmentioning

confidence: 99%

The journey of Zika to the developing brain

et al. 2020

View full text Add to dashboard Cite

Zika virus is a mosquito-borne Flavivirus originally isolated from humans in 1952. Following its re-emergence in Brazil in 2015, an increase in the number of babies born with microcephaly to infected mothers was observed. Microcephaly is a neurodevelopmental disorder, characterised phenotypically by a smaller than average head size, and is usually developed in utero. The 2015 outbreak in the Americas led to the World Health Organisation declaring Zika a Public Health Emergency of International Concern. Since then, much research into the effects of Zika has been carried out. Studies have investigated the structure of the virus, its effects on and evasion of the immune response, cellular entry including target receptors, its transmission from infected mother to foetus and its cellular targets. This review discusses current knowledge and novel research into these areas, in hope of developing a further understanding of how exposure of pregnant women to the Zika virus can lead to impaired brain development of their foetus. Although no longer considered an epidemic in the Americas, the mechanism by which Zika acts is still not comprehensively and wholly understood, and this understanding will be crucial in developing effective vaccines and treatments.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

show abstract

“…A recent study on ZIKV showed that human NPCs (hNPCs) show higher levels of infection (up to 90% higher) than three other viruses . In addition, ZIKV infection causes cytopathic effect without affecting cell viability, decreasing the amount of proteins secreted in mice neural stem cell (NSC) supernatants . This suggests that flavivirus infection may cause the depletion of neural precursors and/or the differentiation of NPCs, leading to neurological sequelae.…”

Section: Nervous System Target Cells Infected By Flavivirusesmentioning

confidence: 99%

Research advancements in the neurological presentation of flaviviruses

Chen

Zhang

et al. 2018

Reviews in Medical Virology

View full text Add to dashboard Cite

Summary Owing to the large‐scale epidemic of Zika virus disease and its association with microcephaly, properties that allow flaviviruses to cause nervous system diseases are an important area of investigation. At present, although potential pathogenic mechanisms of flaviviruses in the nervous system have been examined, they have not been completely elucidated. In this paper, we review the possible mechanisms of blood‐brain barrier penetration, the pathological effects on neurons, and the association between virus mutations and neurotoxicity. A hypothesis on neurotoxicity caused by the Zika virus is presented. Clarifying the mechanisms of virulence of flaviviruses will be helpful in finding better antiviral drugs and optimizing the treatment of symptoms.

show abstract

Zika virus induces astrocyte differentiation in neural stem cells

Cited by 23 publications

References 23 publications

A Fluorescent Cell-Based System for Imaging Zika Virus Infection in Real-Time

A Fluorescent Cell-Based System for Imaging Zika Virus Infection in Real-Time

The journey of Zika to the developing brain

Research advancements in the neurological presentation of flaviviruses

Contact Info

Product

Resources

About