Meq: An MDV-Specific bZIP Transactivator with Transforming Properties

Abstract

The principal cause of chicken T-lymphomas and their accompanying demyelinating disease is infection with Marek’s disease virus (MDV) (Calnek et al. 1997), a herpesvirus. Mareks disease can be prevented by vaccination with an antigenically related nonpathogenic herpesvirus, HVT (turkey herpesvirus). MDV is among the most potent oncogenic herpesviruses, and induces tumors as early as 4 weeks post-inoculation. As such, the virus is likely to encode a direct-acting oncogene or transforming gene. To search for a possible candidate(s), early studies focused on genes expressed in tumor cells or transformed cells. In general, in these cells where there is no virus production, the transcriptional activities are confined to the repeat regions only, which, based on BamHI digestion map, span the BamH, -I2, -Q2, -L, and -A fragments (Ross 1999). Within this region, most of the open reading frames are short and their existence as proteins not conclusively resolved. The exceptions are pp38, ICP4, and Meq, for which the protein products have been clearly identified.It should be noted that most of these studies were carried out using the entire population of tumor cells and cell lines; it is not clear whether all these proteins are expressed in the same or different cell populations. This is an important issue, as in any given latent state, there is usually a fraction of cells, spontaneously releasing viruses, which may contribute to the detection of some lytic gene products. In surveying through the literature, Meq, the focus of this chapter, emerges as one that is most consistently expressed in all tumors and transformed cell lines, both at the transcript and at the protein level. Meq has a structure resembling nuclear oncogenes and, as will be described in detail below, shared properties, characteristic of oncogenes.