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Microenvironment Regulation of Zika Virus Susceptibility in Human Brain Development and Malignant Glioma

Grant number: 223011/Z/21/Z

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Key facts

  • Disease

    Zika virus disease, Congenital infection caused by Zika virus

  • Start & end year

    2023
    2027

  • Known Financial Commitments (USD)

    $1,065,619.32

  • Funder

    Wellcome Trust

  • Principal Investigator

    Dr. Harry JCJ Bulstrode

  • Research Location

    United Kingdom

  • Lead Research Institution

    University of Cambridge

  • Research Priority Alignment

    N/A

  • Research Category

    Pathogen: natural history, transmission and diagnostics

  • Research Subcategory

    Pathogen morphology, shedding & natural history

  • Special Interest Tags

    N/A

  • Study Type

    Non-Clinical

  • Clinical Trial Details

    N/A

  • Broad Policy Alignment

    Pending

  • Age Group

    Not Applicable

  • Vulnerable Population

    Not applicable

  • Occupations of Interest

    Not applicable

Abstract

Neural stem cells (NSCs) in the developing embryo brain share transcription programs with glioma stem cells (GSCs) in malignant brain tumours, and both are susceptible to Zika Virus infection. In the developing brain this can result in microcephaly, whereas in brain tumours it could offer insights relevant to oncolytic virus development. However GSC and NSC susceptibility to Zika and other viruses depends on the microenvironment. In particular, microglia progenitors migrating into the embryo brain from the yolk sac are believed to bring virus with them, whereas my preliminary data suggests that mature tumour-associated microglia instead drive a virus resistance phenotype in GSCs. This project seeks to establish the mechanistic basis for the microenvironment regulation of virus susceptibility in normal and malignant progenitors, and to suggest therapeutic strategies for modulation of these.