Marek's disease (MD), an oncogenic disease caused by Marek's disease herpesvirus (MDHV), can be prevented by immunization with apathogenic herpesvirus of turkeys (HVT). More disease related questions are being pursued by a USDA Special Grants/Animal Health grant. The long-term objective of this more basic project is to determine the nature, processing and function (at the nucleotide-amino acid sequences and antigenic determinant level) of A antigen; a late virus encoded, abundantly expressed, predominately secreted (but also possibly membrane- associated) glycoprotein antigen found in common between MDHV and HVT. This will be done by determining, computer analyzing and comparing nucleotide sequences, and predicted amino-acid sequences, of the MDHV-A gene, and the recently cloned HVT-A gene. DNA sequencing is now being done with a very small USDA Biotechnology/Molecular Biology grant, but more extensive analysis of the data requires new funding. This data will be studied to detect sequences likely to be involved in glycosylation, the body of the message, antigenic determinants, rapid secretion (a signal peptide) and even possible membrane localization. The N-terminal amino acid sequence will be determined directly for comparison with predicted amino acid sequence will be determined directly for comparison with predicted amino acid sequence data to unequivocally identify the signal peptide. Direct comparison of MDHV-A and HVT-A gene DNA sequences will provide definitive information on the genetic similarly of these immunologically related antigens. This comparison will be extended to glycoproteins encoded by other herpesviruses to determine homologies that may be related to conserved function(s). Antigenic domains of MDHV-A and HVT-A will be mapped with monoclonal antibodies, correlated with computer predicted antigenic determinants, and identified as common or unique. The concept that A-antigen is also a membrane antigen will be explored indirectly by determining if its gene has a membrane anchor sequence. If is does, two forms of MDHV-A mRNA will be sought as a possible explanation for one gene encoding both secreted and membrane versions. Attempts will also be made to demonstrate a membrane version of MDHV-A directly, both for completeness and a basis for future membrane biology experiments. The basic scientific information acquired will facilitate learning more about outstanding features of a unique secreted glycoprotein that may also exist is a membrane form, and may play a role in one or more immune phenomena of this herpesvirus oncogenic disease.
| Chen, X B; Velicer, L F (1991) Multiple bidirectional initiations and terminations of transcription in the Marek's disease virus long repeat regions. J Virol 65:2445-51 |
| Coussens, P M; Wilson, M R; Camp, H et al. (1990) Characterization of the gene encoding herpesvirus of turkeys gp57-65: comparison to Marek's disease virus gp57-65 and herpes simplex virus glycoprotein C. Virus Genes 3:291-307 |
