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Title: In vitro characterization of the Meq proteins of Marek's disease virus vaccine strain CV1988

Author
item AJITHDOSS, DHARANI - TEXAS A&M UNIVERSITY
item REDDY, SANJAY - Texas A&M University
item SUCHODOLSKI, PAULETTE - Texas A&M University
item Lee, Lucy
item KUNG, HSING-JIEN - UC DAVIS CANCER CENTER
item LUPIANI, BLANCA - TEXAS A&M UNIVERSITY

Submitted to: Virus Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/13/2009
Publication Date: 6/1/2009
Citation: Ajithdoss, D.K., Reddy, S.M., Suchodolski, P.F., Lee, L.F., Kung, H.J., Lupiani, B. 2009. In Vitro Characterization of the Meq Proteins of Marek's Disease Virus Vaccine Strain CV1988. Virus Research. 142(1-2):57-67.

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); the virus produces a protein called Meq thought to be involved in induction of MD. Earlier studies have shown that the Meq protein of a virulent strain of MDV is essential for causing the disease. The data in this manuscript provides the first evidence that Meq proteins from MDV vaccine strain named CVI988 are generally weak cancer inducers; the data explained the non-cancer causing properties of strain CVI988 of MDV in chickens. This information is essential to develop more effective vaccines against MD.

Technical Abstract: Gallid herpesvirus 2 (GaHV-2), commonly known as Marek’s disease virus serotype-1 (MDV-1), causes T cell lymphoma in chickens. Vaccines prepared from the CVI988/Rispens MDV-1 strain currently offers the best protection. Although, CVI988 is non-oncogenic, it codes for at least two forms of the MDV oncoprotein Meq, and these proteins (CVI-Meq and CVI-L Meq) have not previously been characterized. Here, we report that both CVI-Meq proteins, like the Meq protein of Md5 (a very virulent oncogenic strain) were capable of transforming Rat-2 and NIH3T3 cells. CVI-Meq proteins activated the meq promoter only in the presence of chicken c-Jun (CK-Jun) whereas Md5-Meq activated the same promoter irrespective of CK-Jun co-expression. However, Meq proteins of both Md5 and CVI988 bound the meq promoter in a ChIP assay regardless of whether CK-Jun was co-expressed or not. Domain swapping experiment indicated that both DNA binding and transactivation domains of Md5 Meq are essential for its full transactivation function. Further, site-directed mutagenesis of the Md5-Meq protein showed that amino acid residues at positions 71 and 320 are necessary for increasing transcription from its own promoter. All three Meq proteins activated the MDV gB, MMP-3 and Bcl-2 promoters and suppressed transcription from the MDV pp38/pp14 bidirectional promoter. Collectively, our data suggest that CVI-Meq proteins are generally weak transactivators, what might contribute to non-oncogenic phenotype of CVI988 virus in chickens.