Lineage pathway of human brain progenitor cells identified by JC virus susceptibility.
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.
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Conrad A
CA
Messam
Jean
J
Hou
Richard M
RM
Gronostajski
Eugene O
EO
Major
D001921:Brain / Q000473:pathology* / Q000821:virology*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral; D004198:Disease Susceptibility; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007577:JC Virus / Q000235:genetics / Q000302:isolation & purification*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000235:genetics / Q000473:pathology* / Q000821:virology*; D010957:Plasmids / Q000235:genetics; D027601:Polyomavirus Infections / Q000235:genetics / Q000821:virology*; D015347:RNA Probes / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000473:pathology* / Q000821:virology*; D014162:Transfection / Q000379:methods; D014412:Tumor Virus Infections / Q000235:genetics / Q000821:virology*; D014771:Virion / Q000235:genetics
D017931:DNA Primers; D004279:DNA, Viral; D015347:RNA Probes