2 GENE FAMILIES OF MAREKS-DISEASE VIRUS (MDV) WITH A POTENTIAL ROLE IN TUMOR-INDUCTION IN CHICKEN (REVIEW)

Marek's disease virus (MDV) is one of the most oncogenic herpesviruses and the only cancer virus that has a successful vaccine. Based on the short-latency and polyclonal nature of the tumors, it is likely that MDV encodes its own oncogenes. Recent studies have provided insights into possible MDV genes involved in oncogenesis. We describe the characterization of two gene families encoded by the BamHI-H and I-2 fragments. The BamHI-H and I-2 fragments, located contiguously in the IR(L) region, are unique to oncogenic (serotype) MDV and consistently expressed in MDV-transformed tumors and T-cell lines. The structural alteration of the BamHI-H fragment, specifically the expansion of a 132 bp repeat, has been correlated with the attenuation of the oncogenicity of MDV. Several open-reading frames, some resulting from alternative splicing, can be identified. One of the open-reading frames, BHa, encodes a 7 Kd polypeptide. BHa shares limited homology with a T-cell lymphoma oncogene TLM and stimulates extended growth of chicken embryo fibroblasts, when transfected into the cell. The other gene implicated in latency or oncogenesis is Meg whose coding sequences span portion of the BamHI-I-2 and the Q(2) fragment. Meq has an interesting structure, resembling a chimera between Jun/Fos oncoproteins and WT-1 tumor suppressor protein. It contains a bZIP (basic leucine zipper) domain and a long proline-rich domain. The proline domain has trans-activating function, whereas the bZIP domain allows Meq to dimerize with a variety of transcriptional factors and expands the enhancer repertoire it acts on. As neoplastic transformation usually requires the complementation of multiple oncogenes, BHa and Meq could be two of the proteins participating in this process.