Role of the Leucine Zipper of Marek's Disease Virus Oncoprotein Meq in Pathogenesis
| dc.contributor.advisor | Reddy, Sanjay M. | |
| dc.contributor.committeeMember | Lupiani, Blanca | |
| dc.contributor.committeeMember | Collisson, Ellen | |
| dc.contributor.committeeMember | Porter, Weston | |
| dc.contributor.committeeMember | Tian, Yanan | |
| dc.creator | Suchodolski, Paulette F. | |
| dc.date.accessioned | 2010-07-15T00:13:05Z | |
| dc.date.accessioned | 2010-07-23T21:44:27Z | |
| dc.date.available | 2010-07-15T00:13:05Z | |
| dc.date.available | 2010-07-23T21:44:27Z | |
| dc.date.created | 2009-05 | |
| dc.date.issued | 2010-07-14 | |
| dc.date.submitted | May 2009 | |
| dc.description.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. The MDV genome encodes an oncoprotein, Meq, which shares resemblance with the Jun/Fos family of bZIP transcription factors. Similar to c-Jun, the leucine zipper region of Meq allows the formation of homo- and heterodimers. Meq homo- and heterodimers have different DNA binding affinities and transcriptional activity; therefore, they may differentially regulate transcription of viral and cellular genes. Previous in vitro data has suggested that Meq homodimers may be involved in regulating viral latency/reactivation, while Meq/c-Jun heterodimers are involved in transformation. Therefore, this research investigates the role of Meq homodimers and Meq-Jun heterodimers in the pathogenicity of MDV, by generating chimeric meq genes, which contain the leucine zipper region of the yeast transcription factor GCN4 (meqGCN) or leucine zipper region of c-Fos (meqFos). Thus producing Meq proteins that exclusively homodimerize (MeqGCN) or heterodimerize with Jun family members (MeqFos). Recombinant viruses (rMd5-MeqGCN and rMd5- MeqFos) containing the chimeric genes meqGCN or meqFos, respectively, in place of parental meq were generated with overlapping cosmid clones of Md5, a very virulent MDV strain. The chimeric genes were evaluated in vitro and retained DNA binding and transactivation/repressive functions, however, selected cells expressing MeqGCN and MeqFos had reduced colony formation in soft agar. Both the rMd5-MeqGCN and rMd5- MeqFos viruses replicated in vitro and in vivo, but rMd5-MeqGCN was unable to transform T-cells in infected chickens, while rMd5-MeqFos induced preneoplastic nerve lesions in 50% of infected birds. However, a third virus rMd5-MeqFos/GCN, which contains one copy of each meqGCN and meqFos, induced preneoplastic nerve lesions in 60% of infected chickens and neoplastic lesions in 20% of infected chickens. These data provide the first in vivo evidence that both Meq homodimers and heterodimers are necessary for MDV induced transformation. | en |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/1969.1/ETD-TAMU-2009-05-614 | |
| dc.language.iso | eng | |
| dc.subject | Marek's | en |
| dc.subject | Herpesvirus | en |
| dc.subject | transformation | en |
| dc.subject | oncogene | en |
| dc.title | Role of the Leucine Zipper of Marek's Disease Virus Oncoprotein Meq in Pathogenesis | en |
| dc.type | Book | en |
| dc.type | Thesis | en |
| dc.type.genre | Electronic Dissertation | en |
| dc.type.material | text | en |
| thesis.degree.department | Veterinary Pathobiology | en |
| thesis.degree.discipline | Veterinary Microbiology | en |
| thesis.degree.grantor | Texas A&M University | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |