Epstein-Barr Virus Lytic Infection Induces Retinoic Acid-responsive Genes through Induction of a Retinol-metabolizing Enzyme, DHRS9

Lytic Epstein-Barr virus (EBV) replication occurs in differentiated, but not undifferentiated, epithelial cells. Retinoic acid (RA) induces epithelial cell differentiation. The conversion of retinol into its active form, retinoic acid, requires retinol dehydrogenase enzymes. Here we show that AGS ga...

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Bibliographic Details
Published in:The Journal of biological chemistry 2007-03, Vol.282 (11), p.8317-8324
Main Authors: Jones, Richard J., Dickerson, Sarah, Bhende, Prassana M., Delecluse, Henri-Jacque, Kenney, Shannon C.
Format: Article
Language:English
Subjects:
3-Hydroxysteroid Dehydrogenases
Alcohol Dehydrogenase - metabolism
Burkitt Lymphoma - metabolism
Burkitt Lymphoma - virology
Capsid - metabolism
Cell Differentiation
Cell Line, Tumor
Cytochrome P-450 Enzyme System - metabolism
Epstein-Barr virus
HeLa Cells
Herpesvirus 4, Human - metabolism
Humans
Immunoglobulin G - metabolism
Keratinocytes - cytology
Keratinocytes - virology
Retinoic Acid 4-Hydroxylase
Tretinoin - metabolism
Virus Activation
Virus Latency
Virus Replication
Vitamin A - metabolism
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Summary:Lytic Epstein-Barr virus (EBV) replication occurs in differentiated, but not undifferentiated, epithelial cells. Retinoic acid (RA) induces epithelial cell differentiation. The conversion of retinol into its active form, retinoic acid, requires retinol dehydrogenase enzymes. Here we show that AGS gastric carcinoma cells containing the lytic form of EBV infection have enhanced expression of a gene (DHRS9) encoding an enzyme that mediates conversion of retinol into RA. DHRS9 expression is also increased following induction of lytic viral infection in EBV-positive Burkitt lymphoma cells. We demonstrate that the EBV immediate-early protein, BZLF1, activates the DHRS9 promoter through a direct DNA binding mechanism. Furthermore, BZLF1 expression in AGS cells is sufficient to activate DHRS9 gene expression and increases the ability of retinol to induce the RA-responsive gene, CYP26A1. Production of RA during the lytic form of EBV infection may enhance viral replication by promoting keratinocyte differentiation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M608667200