Lineage pathway of human brain progenitor cells identified by JC virus susceptability

Authors

  • Conrad A. Messam PhD,

    1. Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
    Current affiliation:
    1. Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
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  • Jean Hou BS,

    1. Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Richard M. Gronostajski PhD,

    1. Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY
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  • Eugene O. Major PhD

    Corresponding author
    1. Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
    • Laboratory of Molecular Medicine and Neuroscience, NINDS, NIH, 36 Convent Drive, Building 36, Room 5W21, Bethesda, MD 20892
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  • This article is a US Government work and, as such, is in the public domain in the United States of America.

Abstract

Multipotential human central nervous system progenitor cells, isolated from human fetal brain tissue by selective growth conditions, were cultured as undifferentiated, attached cell layers. Selective differentiation yielded highly purified populations of neurons or astrocytes. This report describes the novel use of this cell culture model to study cell type–specific recognition of a human neurotropic virus, JC virus. Infection by either JC virions or a plasmid encoding the JC genome demonstrated susceptibility in astrocytes and, to a lesser degree, progenitor cells, whereas neurons remained nonpermissive. JC virus susceptibility correlated with significantly higher expression of the NFI-X transcription factor in astrocytes than in neurons. Furthermore, transfection of an NFI-X expression vector into progenitor-derived neuronal cells before infection resulted in viral protein production. These results indicate that susceptibility to JC virus infection occurs at the molecular level and also suggest that differential recognition of the viral promoter sequences can predict lineage pathways of multipotential progenitor cells in the human central nervous system. Ann Neurol 2003

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