Epstein-Barr Virus B Cell Growth Transformation: The Nuclear Events.

Epstein-Barr virus (EBV) is the first human DNA tumor virus identified from African Burkitt's lymphoma cells. EBV causes ~200,000 various cancers world-wide each year. EBV-associated cancers express latent EBV proteins, EBV nuclear antigens (EBNAs), and latent membrane proteins (LMPs). EBNA1 tethers EBV episomes to the chromosome during mitosis to ensure episomes are divided evenly between daughter cells. EBNA2 is the major EBV latency transcription activator. It activates the expression of other EBNAs and LMPs. It also activates MYC through enhancers 400-500 kb upstream to provide proliferation signals. EBNALP co-activates with EBNA2. EBNA3A/C represses CDKN2A to prevent senescence. LMP1 activates NF-κB to prevent apoptosis. The coordinated activity of EBV proteins in the nucleus allows efficient transformation of primary resting B lymphocytes into immortalized lymphoblastoid cell lines in vitro.