GENETIC DETERMINANT OF RAPID-ONSET B-CELL LYMPHOMA BY AVIAN-LEUKOSIS VIRUS

Infection of 10 day-old chicken embryos with the recombinant avian leu kosis virus (ALV) EU-8 induces a high incidence of rapid-onset B-cell lymphoma by insertional activation of the c-myb gene, LR-9, a related ALV with differences from EU-8 in the gag and pol genes, induces rapid -onset lymphoma at only a low incidence, To localize the viral determi nant(s) responsible for this biologic difference, we constructed and t ested a series of reciprocal chimeras between EU-8 and LR-9 ALVs. The ability to induce rapid-onset lymphoma efficiently was localized to a 925-nucleotide (nt) region of the EU-8 gag gene, Sequence analysis of this region revealed a 42-nt deletion in EU-8 relative to LR-9, as wel l as some single-nucleotide changes. A mutant virus, Delta LR-9, const ructed by deleting these 42 nt from LR-9, also induced rapid-onset lym phoma at a high frequency, confirming the biologic significance of thi s deletion, This deletion removed nt 735 to 776, which lies within a c is-acting RNA element that negatively regulates splicing (NRS), The de letion was shown to cause an increase in splicing efficiency, which ma y lead to increased production of a truncated myb gene product from an ALV-myb readthrough RNA.