Submitted to: Proceedings of the National Academy of Sciences
Publication Type: Peer reviewed journal
Publication Acceptance Date: 7/1/2004
Publication Date: 8/10/2004
Citation: Lupiani, B.M., Lee, L.F., Cui, X., Gimeno, I.M., Anderson, A., Morgan, R.W., Silva, R.F., Witter, R.L., Kung, H., Reddy, S. 2004. Marek's disease virus-encoded Meq gene is involved in transformation of lymphocytes but is dispensable for replication. Proceedings of the National Academy of Sciences. 101(32):11815-11820. Interpretive Summary: Marek's disease (MD), a virus-induced cancer-like disease in chickens, is considered a major disease problem in commercial poultry. Vaccination has dramatically reduced the incidence of the disease, but very little is known about the basic mechanisms involved in the induction of disease. The objective of this research was to molecularly characterize Marek's disease virus (MDV) so that successful programs to control the disease can be developed. We have discovered a unique gene (genetic building block) termed MEQ which has been thought to be involved in induction of cancer in chicken for over a decade. This paper is the first to define MEQ as a cancer causing gene and is indispensable for tumor induction. This important information will undoubtedly help industry with a possible vaccine for better control of the disease. It also helps scientists in academia better understand the function of this viral gene.
Technical Abstract: Marek's disease virus (MDV) causes an acute lymphoproliferative disease in chickens resulting in T-cell lymphomas in visceral organs and major nerves tracks. Earlier studies have determined that the repeat regions of oncogenic serotype 1 MDV encode a basic leucine zipper (bZIP) protein, Meq, which structurally resembles the Jun/Fos family of transcriptional activators. In addition, Meq is consistently expressed in MDV induced tumor cells and has been suggested as the MDV associated oncogene. To study the function of Meq, we have generated a Meq null mutant virus by deleting both copies of the meq gene from the genome of a very virulent strain of MDV. Growth curves in cultured fibroblasts indicated that Meq is dispensable for in vitro virus replication. In vivo replication in lymphoid organs and feather follicular epithelium was also not impaired suggesting that Meq is dispensable for lytic infection in chickens. Reactivation of the Meq null mutant virus from peripheral blood lymphocytes was reduced suggesting that Meq is involved in latency. Pathogenesis experiments showed that the Meq null mutant virus was fully attenuated in chickens since none of the infected chickens developed Marek's disease associated lymphomas, suggesting that Meq is involved in lymphocyte transform. A revertant virus, which restored the expression of the meq gene, showed properties similar to that of the parental virus, confirming that Meq is involved in transformation but not in lytic replication in chickens.