Transcriptional interaction between retroviral long terminal repeats (LTRs): mechanism of 5' LTR suppression and 3' LTR promoter activation of c-myc in avian B-cell lymphomas

Abstract

Chicken syncytial viruses induce bursal lymphomas by integrating into the c-myc locus and activating myc expression by 3' long terminal repeat (LTR) promoter insertion. In contrast to wild-type proviruses, in which transcription initiates predominantly in the 5'LTR, these myc-associated proviruses exhibit a predominance of transcription from the 3' LTR and little transcription from the 5' LTR. Most of these proviruses contain deletions within the 5' end of their genome that spare the 5' LTR. We report the identification of a 0.3-kb viral leader sequence that modulates 5' and 3' LTR transcriptional activities. In the presence of this sequence, transcription from the 5' LTR predominates, but in its absence, the 3' LTR promoter becomes activated, resulting in a high level of myc expression. This viral sequence does not behave like a classical enhancer; it activates transcription only when located downstream from the promoter and in the sense orientation. In this regard, it resembles the recently described human immunodeficiency virus RNA enhancer. This study suggests that retroviruses contain internal sequences which directionally activate the 5' LTR promoter to facilitate transcription of the viral genome and that deletion of these sequences is one step in the activation of the 3' LTR of myc-associated proviruses in avian bursal lymphomas.