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

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.