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Differential gene expression patterns of EBV infected EBNA-3A positive and negative human B lymphocytes.
PLoS Pathog. 5:e1000506 (2009)
The genome of Epstein-Barr virus (EBV) encodes 86 proteins, but only a limited set is expressed in EBV-growth transformed B cells, termed lymphoblastoid cell lines (LCLs). These cells proliferate via the concerted action of EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), some of which are rate limiting to establish a stable homeostasis of growth promoting and anti-apoptotic activities. We show here that EBV mutants, which lack the EBNA-3A gene, are impaired but can still initiate cell cycle entry and proliferation of primary human B cells in contrast to an EBNA-2 deficient mutant virus. Surprisingly, and in contrast to previous reports, these viral mutants are attenuated in growth transformation assays but give rise to permanently growing EBNA-3A negative B cell lines which exhibit reduced proliferation rates and elevated levels of apoptosis. Expression profiles of EBNA-3A deficient LCLs are characterized by 129 down-regulated and 167 up-regulated genes, which are significantly enriched for genes involved in apoptotic processes or cell cycle progression like the tumor suppressor gene p16/INK4A, or might contribute to essential steps of the viral life cycle in the infected host. In addition, EBNA-3A cellular target genes remarkably overlap with previously identified targets of EBNA-2. This study comprises the first genome wide expression profiles of EBNA-3A target genes generated within the complex network of viral proteins of the growth transformed B cell and permits a more detailed understanding of EBNA-3A's function and contribution to viral pathogenesis.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
EPSTEIN-BARR-VIRUS; NUCLEAR ANTIGEN 3C; LYMPHOBLASTOID CELL-LINE; RBP-J-KAPPA; BURKITTS-LYMPHOMA; TARGET GENES; PROTEIN; PROMOTER; EBNA3A; GROWTH
ISSN (print) / ISBN
1553-7366
e-ISSN
1553-7374
Journal
PLoS Pathogens
Quellenangaben
Volume: 5,
Issue: 7,
Article Number: e1000506
Publisher
Public Library of Science (PLoS)
Non-patent literature
Publications
Reviewing status
Peer reviewed