B-lymphoma induction by reticuloendotheliosis virus: characterization of a mutated chicken syncytial virus provirus involved in c-myc activation

Nondefective reticuloendotheliosis virus induces chicken bursal lymphoma in a manner similar to that of avian leukosis virus. The provirus integrates in the c-myc locus and uses a promoter insertion mechanism to activate c-myc expression. We cloned a provirus involved in c-myc activation from a B lymphoma. Detailed structural characterization of this clone, including sequence determination, revealed proviral insertion at 512 base pairs preceding the second c-myc exon. The provirus has a deletion of 80% of the viral genes but retains two intact long terminal repeats (LTRs). A segment of the viral env sequence is present in an inverted orientation. Elevated expression of c-myc, apparently directed by the 3' LTR, was detected. However, despite the presence of an intact 5' LTR, no viral transcripts were detected. Thus, the internal proviral rearrangement can affect 5' LTR transcription or stability of the message or both. This finding is in consonance with the view that proviral deletion plays an important role in the induction of bursal lymphomas by nonacute retroviruses.