Differential Gene Expression Patterns of EBV Infected EBNA-3A Positive and Negative Human B Lymphocytes

PLoS Pathogens

Sabine Petermann¹  Sabine Maier¹  Marie L. Hertle¹  Claudia Popp¹  Roland Lang²  Bettina Kempkes³  Jörg Mages³  Elisabeth Kremmer⁴ 

[1] Department of Gene Vectors, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany;Institute of Clinical Microbiology, Immunology and Hygiene, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany;Institute of Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany;Institute of Molecular Immunology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany

关键词: B cells;    Apoptosis;    Cell cycle;    cell division;    Gene regulation;    Reverse transcriptase-polymerase chain reaction;    Gene expression;    Cell cultures;    Fibroblasts;   

DOI  :  10.1371/journal.ppat.1000506

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY