The CR4 region of EBNA2 confers viability of Epstein-Barr virus-transformed B cells by CBF1-independent signalling.
The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) gene product is the key regulator of the latent genes of EBV and essential for EBV-mediated transformation of human primary B cells. Viral mutants were constructed carrying a deletion of the EBNA2 conserved region 4 (CR4). Primary resting B cells infected with the DeltaCR4-EBNA2 mutant virus were dramatically impaired for B cell transformation. Lymphoblastoid cell lines (LCLs) established with this mutant EBV revealed a prolonged population doubling time when cells were cultivated at low cell densities, which are not critical for wild-type-infected cells. Low-level spontaneous cell death occurred when the cells were cultivated at suboptimal cell densities. The phenotype of B cells and LCLs infected with the DeltaCR4-EBNA2 mutant virus indicated that the CR4 region of EBNA2 specifically contributes to the viability of the cells rather than affecting cell division rates.
Grabusic
Kristina
K
GSF - National Research Center for Environment and Health, Institute of Clinical Molecular Biology, Marchioninistr. 25, D-81377 Munich, Germany.
Maier
Sabine
S
GSF - National Research Center for Environment and Health, Institute of Clinical Molecular Biology, Marchioninistr. 25, D-81377 Munich, Germany.
Hartmann
Andrea
A
GSF - National Research Center for Environment and Health, Institute of Clinical Molecular Biology, Marchioninistr. 25, D-81377 Munich, Germany.
Mantik
Anja
A
GSF - National Research Center for Environment and Health, Institute of Clinical Molecular Biology, Marchioninistr. 25, D-81377 Munich, Germany.
Hammerschmidt
Wolfgang
W
Department of Gene Vectors, Marchioninistr. 25, D-81377 Munich, Germany.
Kempkes
Bettina
B
GSF - National Research Center for Environment and Health, Institute of Clinical Molecular Biology, Marchioninistr. 25, D-81377 Munich, Germany.
D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology; D002470:Cell Survival; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D017124:Conserved Sequence / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D017353:Gene Deletion; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism*; D015398:Signal Transduction
D019309:Epstein-Barr Virus Nuclear Antigens; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497570:RBPJ protein, human