Identifying the Zika Virus Target Cell in Malignant Glioma

Abstract The Zika Virus epidemic of 2015–2016 was associated with striking failure of forebrain development in infants born to infected mothers, resulting in microcephaly. Studies from numerous labs subsequently confirmed a selective effect of the virus on neural stem cell survival, self-renewal and...

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Published inNeuro-oncology (Charlottesville, Va.) Vol. 21; no. Supplement_4; p. iv2
Main Authors Girdler, Gemma, Gracia, Tannia, Fountain, Daniel, Fajardo Jr, Ted, Finlay, Jack, Hallou, Clément, Pollard, Steve, Sweeney, Trevor, Gergely, Fanni, Rowitch, David, Bulstrode, Harry
Format Journal Article
LanguageEnglish
Published US Oxford University Press 12.10.2019
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Abstract Abstract The Zika Virus epidemic of 2015–2016 was associated with striking failure of forebrain development in infants born to infected mothers, resulting in microcephaly. Studies from numerous labs subsequently confirmed a selective effect of the virus on neural stem cell survival, self-renewal and differentiation. The glioma stem cells which drive glioblastoma and other malignant gliomas depend on neural stem cell transcription programs, so that understanding Zika infection in these cells promises valuable insights into future therapy. We describe here: 1) Study of low passage patient-derived glioblastoma cell lines and normal neural stem cells (CRUK Glioma Cellular Genetics Resource) in adherent culture to address the influence of glioma subtype on infectability 2) Application of genetically modified mCherry reporter Zika Virus strains to address the Zika target cell in glioblastoma. 3) Development of a cerebral organoid model to interrogate the differential effects of the virus on tumour cells and surrounding normal brain. 4) Demonstration of Zika infection on primary patient derived tissue in slice culture format Using these tools we find that Zika targets a common stem cell population across tumour subtypes and neural stem cell controls, and in embryonic and primary tumour explants, and that infection is influenced by activity of cholesterol biosynthesis pathways.
AbstractList The Zika Virus epidemic of 2015–2016 was associated with striking failure of forebrain development in infants born to infected mothers, resulting in microcephaly. Studies from numerous labs subsequently confirmed a selective effect of the virus on neural stem cell survival, self-renewal and differentiation. The glioma stem cells which drive glioblastoma and other malignant gliomas depend on neural stem cell transcription programs, so that understanding Zika infection in these cells promises valuable insights into future therapy. We describe here: 1) Study of low passage patient-derived glioblastoma cell lines and normal neural stem cells (CRUK Glioma Cellular Genetics Resource) in adherent culture to address the influence of glioma subtype on infectability 2) Application of genetically modified mCherry reporter Zika Virus strains to address the Zika target cell in glioblastoma. 3) Development of a cerebral organoid model to interrogate the differential effects of the virus on tumour cells and surrounding normal brain. 4) Demonstration of Zika infection on primary patient derived tissue in slice culture format Using these tools we find that Zika targets a common stem cell population across tumour subtypes and neural stem cell controls, and in embryonic and primary tumour explants, and that infection is influenced by activity of cholesterol biosynthesis pathways.
Abstract The Zika Virus epidemic of 2015–2016 was associated with striking failure of forebrain development in infants born to infected mothers, resulting in microcephaly. Studies from numerous labs subsequently confirmed a selective effect of the virus on neural stem cell survival, self-renewal and differentiation. The glioma stem cells which drive glioblastoma and other malignant gliomas depend on neural stem cell transcription programs, so that understanding Zika infection in these cells promises valuable insights into future therapy. We describe here: 1) Study of low passage patient-derived glioblastoma cell lines and normal neural stem cells (CRUK Glioma Cellular Genetics Resource) in adherent culture to address the influence of glioma subtype on infectability 2) Application of genetically modified mCherry reporter Zika Virus strains to address the Zika target cell in glioblastoma. 3) Development of a cerebral organoid model to interrogate the differential effects of the virus on tumour cells and surrounding normal brain. 4) Demonstration of Zika infection on primary patient derived tissue in slice culture format Using these tools we find that Zika targets a common stem cell population across tumour subtypes and neural stem cell controls, and in embryonic and primary tumour explants, and that infection is influenced by activity of cholesterol biosynthesis pathways.
Author Fajardo Jr, Ted
Finlay, Jack
Girdler, Gemma
Hallou, Clément
Bulstrode, Harry
Sweeney, Trevor
Gracia, Tannia
Pollard, Steve
Fountain, Daniel
Gergely, Fanni
Rowitch, David
AuthorAffiliation 6 Salford Royal NHS Foundation Trust, Dept of Neurosurgery , Salford, United Kingdom
2 Cancer Research UK Cambridge Institute, University of Cambridge , Cambridge, United Kingdom
3 MRC Centre for Regenerative Medicine and Edinburgh Cancer Research Centre , Edinburgh, United Kingdom
5 Wellcome-MRC Stem Cell Institute, Department of Paediatrics, University of Cambridge , Cambridge, United Kingdom
1 Wellcome-MRC Stem Cell Institute, Dept of Clinical Neuroscience, Cambridge University , Cambridge, United Kingdom
4 Division of Virology, Department of Pathology, University of Cambridge , Cambridge, United Kingdom
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– name: 1 Wellcome-MRC Stem Cell Institute, Dept of Clinical Neuroscience, Cambridge University , Cambridge, United Kingdom
– name: 2 Cancer Research UK Cambridge Institute, University of Cambridge , Cambridge, United Kingdom
– name: 4 Division of Virology, Department of Pathology, University of Cambridge , Cambridge, United Kingdom
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Copyright The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2019
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Snippet Abstract The Zika Virus epidemic of 2015–2016 was associated with striking failure of forebrain development in infants born to infected mothers, resulting in...
The Zika Virus epidemic of 2015–2016 was associated with striking failure of forebrain development in infants born to infected mothers, resulting in...
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Title Identifying the Zika Virus Target Cell in Malignant Glioma
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