|Suchodolski, Paulette -|
|Izumiya, Yoshihiro -|
|Lupiani, Blanca -|
|Ajithdoss, Dharani -|
|Kung, Hsing-Jien -|
|Reddy, Sanjay -|
Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 5, 2010
Publication Date: April 10, 2010
Citation: Suchodolski, P.F., Izumiya, Y., Lupiani, B., Ajithdoss, D.K., Lee, L.F., Kung, H., Reddy, S.M. 2010. Both Homo and Heterodimers of Marek's Disease Virus Encoded Meq Protein Contribute to Transformation of Lymphocytes in Chickens. Virology. 399(2):312-321. 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) and it produces a protein called Meq thought to be involved in cancer-like disease in chickens. Earlier studies have shown that the Meq protein functions by binding to certain proteins in the chicken host. In this report, we showed that these interactions are essential for causing cancer-like disease in chickens. The data in this manuscript provides the first evidence that Meq interaction with cellular proteins is crucial for disease progression.
Technical Abstract: Marek’s disease virus (MDV) elicits T-cell lymphomas in chickens. The MDV genome encodes an oncoprotein, Meq, with similarity to the Jun/Fos family of proteins. Similar to Jun, the leucine zipper region of Meq allows the formation of homo- and heterodimers. We have previously shown that Meq homodimers are not sufficient to induce transformation in vivo. In this study, we investigated the role of Meq heterodimers in the pathogenicity of MDV by generating a chimeric meq gene, which contains the leucine zipper region of Fos (meqFos). A recombinant virus containing the chimeric meqFos gene in place of parental meq, rMd5-MeqFos, was not capable of transforming lymphocytes in chickens, indicating that heterodimerization of Meq alone is not sufficient for transformation. In addition, the recovery of oncogenic phenotype by a recombinant virus encoding one copy each of MeqGCN (homodimer) and MeqFos (heterodimer) conclusively demonstrates that both homo and heterodimerization are required for oncogenesis.