Epstein-Barr Virus EBNA-2 gene expression enhances lymphotoxin production by B lymphocytes

Epstein-Barr Virus (EBV) effectively transforms B lymphocytes into long-term cell lines or tumors through the interaction of viral gene products and cellular proteins induced secondary to the virus infection. The latent membrane protein (LMP) gene, the EBV nuclear antigens (EBNAs) 1 and 2, and the origin of replication genes of the virus are the principal viral effectors of transformation. One of the cellular proteins that enhances the growth and proliferation of B cells is lymphotoxin (LT). We have found that Burkitt's lymphoma cells containing a strain of EBV with a deletion in EBNA-2 had lower constitutive and inducible levels of LT compared to LT production in Burkitt's cells with competent EBV or lymphoblastoid cell lines actively producing EBV. Also, the LT production in the latter cell lines was greater than in cells in which the infecting EBV had a deletion in the LMP gene. The relative decrease in LT production associated with deletions in the LMP was less than that found with EBNA-2 deletions. Overall our results indicate that the EBNA-2 gene enhances the capacity of EBV-infected cells to produce LT.