Loss of Marek's disease virus tumorigenicity is associated with truncation of RNAs transcribed within BamHI-H

Abstract

The attenuation of Marek's disease virus (MDV) is associated with loss of pathogenicity and tumorigenicity. Previous studies have demonstrated a strong correlation between attenuation and amplification of a specific sequence located within the MDV terminal and internal repeats. We recently reported that the regions containing the amplified sequences, the BamHI D and H fragments, were transcriptionally active. However, differential transcription activity was observed to exist between attenuated and pathogenic MDV strains. Specifically, a major transcript of 1.8 kilobases was found to be produced by pathogenic MDV and not by attenuated MDV. We now report that the disappearance of this transcript is concomitant with the production of a 0.4-kilobase RNA, an RNA resulting from the truncation of the tumorigenicity-related transcript.

Retention of oncogenicity by a Marek's disease virus mutant lacking six unique short region genes

“…Oncogenic MDV strains do not replicate well in cell culture and become attenuated rapidly during serial passage (10). Attenuation is accompanied by alterations in the sequence and expression of the MDV genome (3,4,13,21,41,44), loss of horizontal transmission (10), and a decreased ability to infect lymphocytes in vivo and in vitro (39).…”

“…These approaches have led to the identification of a number of MDV genes and regions having possible significance for transformation. The repeats (terminal and inverted, respectively) flanking the unique long (UL) region of the MDV genome (TR L and IR L ) encode a family of RNAs that become disrupted during attenuation (3,4). This region also contains the meq gene, which encodes a leucine-zipper-containing protein expressed in LBCLs (18).…”

Structural analysis and transcriptional mapping of the Marek's disease virus gene encoding pp38, an antigen associated with transformed cells

“…Several laboratories demonstrated that the amplification of a 132-bp repeat in this region during prolonged passages of MDV correlates with the attenuation of viral oncogenicity (15,25,37). Bradley et al (3,4) further showed that expansion of this region results in the disruption of a 1.8-kb transcript(s) and suggested that this transcript is involved in MDV-induced transformation. Other transcripts that are initiated or terminated near the 132-bp repeat region have also been described (6).…”

“…To further characterize this antigen, we proceeded to identify two Xgtll (gtll) clones (GA8 and RA2), derived from the MDV genome, that react with this monoclonal antibody (9). These two clones map within the BamHI H fragment at a region close to the 1.8-kb transcription unit (3,4,20). We also raised antisera against the recombinant B-galactosidase-MDV fusion proteins of these two clones.…”

“…pp38 is a 290-amino-acid protein, rich in acidic residues, and is translated from an unspliced message. Interestingly, its promoter-enhancer overlaps that of the transformation-related 1.8-kb gene family (3,4,20). The pp38 gene and the 1.8-kb transcript apparently form a divergent transcription unit and are thus likely to be coordinately regulated.…”