Epstein-Barr Virus (EBV) EBNA and LMP proteins and the viral miRNAs cause growth of infected human B lymphocytes, giving cells which resemble some lymphomas observed in immunodeficient patients. Infection of human T lymphocytes may also occur with some strains of EBV. EBV associated cancers in immunocompetent patients involve altered expression or mutation of cell genes in combination with some EBV gene functions. Immune evasion mechanisms play important roles in the normal virus life cycle and in cancers of immunocompetent patients.
The EBV genome can express over 100 gene products. After sequencing the EBV from many normal and cancer cell infections worldwide, we analysed a multiple sequence alignment of 241 EBV genomes. The largest variation is between type 1 and type 2 EBV, mediated by sequence difference in the EBNA2 and EBNA3 regions of the genome. Although type 1 EBV is much more effective at transforming B cells than type 2 EBV, both types can be involved in cancers. The greater ability of type 1 EBV to transform human B lymphocytes is partly due to a weaker interaction of type 1 EBNA2 with the cell BS69 protein. BS69 can obstruct the transcription factor activity of EBNA2. Searching for virus sequence variation that is linked to cancer development has identified a single nucleotide variation which creates an additional NFAT site in the promoter for the EBV BZLF1 virus replication activator. Strains with this variation activate virus replication more strongly and are enriched in EBV associated cancers.