Molecular analysis of the glycoprotein C-negative phenotype of attenuated Marek's disease virus

Serial passage of oncogenic serotype 1 Marek's Disease virus (MDV) in cultured avian cells results in attenuation of viral oncogenicity and pathogenicity. Coincident with attenuation, expression of MDV glycoprotein C (gC) is significantly reduced. Regulation of MDV gC may have important implications for virus-host interactions and have important consequences in the process of viral attenuation. To investigate the mechanism by which MDV gC expression is reduced during attenuation of the very virulent serotype 1 MDV strain Md11, protein levels, gene structure, steady-state RNA levels, and transcription rates of MDV gC from oncogenic and attenuated isolates of Md11 were determined. Comparison of these data with similar studies on MDV proteins whose expression is not altered during attenuation indicates that reduced expression of MDV gC is directly related to reduction in transcription rate of the MDV gC gene in attenuated Md11. Reduced transcription rates and lack of any gross structural alterations in the attenuated MDV gC gene suggest that MDV regulatory protein(s) which interact with the MDV gC promoter are altered during attenuation of MDV strain Md11. This conclusion is supported by DNA sequence data which indicate that the promoters of oncogenic and attenuated Md11 gC genes are identical.