Homodimerization of Marek's disease virus encoded Meq protein is not sufficient for transformation of lymphocytes in chicken

Authors: SUCHODOLSKI, PAULETTE - Texas A&M University; IZUMIYA, YOSHIHIRO - Davis Cancer Research Center; LUPIANI, BLANCA - Texas A&M University; AJITHDOSS, DHARANI - Texas A&M University; GILAD, OREN - Davis Cancer Research Center; Lee, Lucy; KUNG, HSING - Davis Cancer Research Center; REDDY, SANJAY - Texas A&M University

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/21/2008
Publication Date: 1/15/2009
Citation: Suchodolski, P., Izumiya, Y., Lupiani, B., Ajithdoss, D.K., Gilad, O., Lee, L.F., Kung, H-J, Reddy, S.M. 2009. Homodimerization of Marek's Disease Virus-Encoded Meq Protein Is Not Sufficient for Transformation of Lymphocytes in Chickens. Journal of Virology. 83(2):859-869.

Interpretive Summary: Marek's disease (MD), a virus-induced cancer-like disease of chickens, is a major disease problem in commercial poultry. This disease is caused by a virus called Marek’s disease virus (MDV) that produces a protein called Meq thought to be involved in induction of cancer. Earlier studies have shown that the Meq protein functions by binding to certain proteins in the chicken. In this report, we showed that these interactions are essential for causing MD in chickens. The data in this manuscript provides the first evidence that Meq interaction with cellular host proteins is crucial for disease progression.

Technical Abstract: Marek’s disease virus (MDV), the etiologic agent of Marek’s disease, is a potent oncogenic herpesvirus. MDV is highly contagious and elicits a rapid onset of malignant T-cell lymphomas in chickens within several weeks after infection. MDV codes for an oncoprotein, Meq, which shares resemblance with the Jun/Fos family of b-ZIP transcription factors and similar to Jun, the leucine zipper region of Meq allows the formation of homo and heterodimers. Earlier studies indicate that Meq homo and heterodimers have different DNA binding affinities and transcriptional activity and, therefore, may differentially mediate transcription regulation of viral and cellular genes. In order to study the role of Meq homodimers in the pathogenicity of MDV, a chimeric meq gene, containing the leucine zipper region of the yeast transcription factor GCN4 (meqGCN), which allows b-ZIP proteins to only form homodimers, was generated. A recombinant virus (rMd5-MeqGCN) containing the chimeric meqGCN gene in place of parental meq was generated using overlapping cosmid clones of Md5, a very virulent MDV. The rMd5-MeqGCN virus replicated in vitro, in cultured fibroblasts, and in vivo, but was unable to transform T-cells in infected chickens. This data provides the first in vivo evidence that Meq homodimers are not sufficient for MDV induced transformation.