Epstein-Barr virus nuclear antigen-1 and myc cooperate in lymphomagenesis

The lymphomagenic action of myc genes in conjunction with Epstein-Barr virus nuclear antigen-I (EBNA-I) have been examined using transgenic mice in several separate tests. Synergy between Myc and EBNA-I in lymphomagenesis was revealed in a cross breed study where co-expression of transgenic myc and EBNA-I led to a tumor latency period reduced significantly in some crosses. In the resulting bitransgenic tumors, expression of the Eμ-myc genes was not affected by EBNA-I expression. MoMLV was utilized as a transposon tag to activate cellular oncogenes by infection of EμEBNA-I mice. Rearrangement at the c-myc locus in B cell tumors from these mice again suggests a cooperative action between myc and EBNA-I. Tumors arising in EμEBNA-I mice typically showed a trisomy of chromosome 15, upon which the c-myc locus resides. Bitransgenic tumors (EBNA-I/c-myc) did not show trisomy 15. This raises the possibility that amplification of c-myc is factorial in the selection of trisomy 15 in these tumors. These data indicate that myc and EBNA-I act cooperatively and are not redundant in lymphomagenesis. Expression of EBNA-I by EBV may provide a selection pressure in addition to translocation of the c-myc locus in the genesis of endemic Burkitt's lymphoma (BL).