Transcriptional regulation of ALV bursal lymphomagenesis

Avian leukosis virus (ALV) induces bursal lymphoma in chickens after rare integration of proviral long terminal repeat (LTR) sequences next to the c-myc proto-oncogene. Labile LTR-binding proteins are essential for c-myc hyperexpression, since LTR-enhanced transcription, as well as the activity of the LTR-binding proteins, is specifically decreased following protein synthesis inhibition. This lability is restricted to hematopoetic cells of ALV-susceptible chicken strains, suggesting that the labile proteins play an important role in susceptibility to lymphomagenesis. Five proteins that interact with the ALV LTR enhancer were identified from bursal lymphoma cells: two proteins are stable (b and c), while three proteins (a1, a3, and b*) are labile in pre-B cell types. Two cDNAs (a1/EBP and a3/EBP) encoding leucine zipper proteins that bind to the ALV LTR enhancer were cloned using a lambda gt11 cDNA expression library made from bursal lymphoma cells. We are presently studying the roles of a1/EBP and a3/EBP in labile regulation of LTR-enhanced c-myc transcription and susceptibility to bursal lymphomagenesis.