Quiescent JCV in human neural progenitor cells is activated during lineage differentiation to astrocytes

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NINDS	VIROL-5

Authors

• M.W. Ferenczy
• L.J. Marshall
• E.O. Major

Abstract

JC Virus (JCV), the etiological agent of the human brain demyelinating disease progressive multifocal leukoencephalopathy, can non-productively infect multipotential human neural progenitor cells. Upon serum-induced differentiation of infected progenitor cells to astrocytes, JCV commenced early gene expression, followed by DNA replication and late gene expression. Measuring changes in gene expression during the course of astrocyte differentiation provides insight into factors required in the transcription and replication of JCV. We have used Affymetrix microarrays to determine the expression of over 25,000 genes at multiple times during astrocyte differentiation from neural progenitor cells. RNA for the astrocyte markers glial fibrillary acidic protein (GFAP), secreted protein, acidic and rich in cysteines-like 1 (SPARC-L1), and the astrocyte specific glutamate transporter SLC1A2 were upregulated within 24 hours of differentiation and remained upregulated. During astrocyte differentiation, the transcription factors nuclear factor I-A (NFI-A) was downregulated, and NFI-X was upregulated, as previously shown, demonstrating the reproducibility of the differentiation. These changes coincide with increasing JCV susceptibility during differentiation, adding further evidence to the observation that NFI-A represses JCV, while NFI-X enhances infection. This model of JCV infection followed by astrocyte differentiation may lead to the identification of a number of proteins that are important for JCV pathogenesis.

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