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Science. 2017 Jul 7;357(6346):83-88. doi: 10.1126/science.aam9243. Epub 2017 Jun 1.

Neurodevelopmental protein Musashi-1 interacts with the Zika genome and promotes viral replication.

Author information

1
Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.
2
Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
3
Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
4
Department of Medicine, University of Cambridge, Hills Road, Cambridge CB2 2QQ, UK.
5
Faculty of Biological Sciences, Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
6
Department of Human Genetics, Radboud University Medical Centre, Nijmegen, Netherlands.
7
Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK.
8
Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK. fanni.gergely@cruk.cam.ac.uk.

Abstract

A recent outbreak of Zika virus in Brazil has led to a simultaneous increase in reports of neonatal microcephaly. Zika targets cerebral neural precursors, a cell population essential for cortical development, but the cause of this neurotropism remains obscure. Here we report that the neural RNA-binding protein Musashi-1 (MSI1) interacts with the Zika genome and enables viral replication. Zika infection disrupts the binding of MSI1 to its endogenous targets, thereby deregulating expression of factors implicated in neural stem cell function. We further show that MSI1 is highly expressed in neural progenitors of the human embryonic brain and is mutated in individuals with autosomal recessive primary microcephaly. Selective MSI1 expression in neural precursors could therefore explain the exceptional vulnerability of these cells to Zika infection.

PMID:
28572454
PMCID:
PMC5798584
DOI:
10.1126/science.aam9243
[Indexed for MEDLINE]
Free PMC Article

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