This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Petherbridge, L. Articles by Nair, V. Search for Related Content PubMed PubMed Citation Articles by Petherbridge, L. Articles by Nair, V.

Replication-Competent Bacterial Artificial Chromosomes of Marek's Disease Virus: Novel Tools for Generation of Molecularly Defined Herpesvirus Vaccines

Viral Oncogenesis Group, Institute for Animal Health, Compton, Berkshire, RG20 7NN, United Kingdom,¹ Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853,² and Federal Research Center for Virus Diseases of Animals, D-17493 Greifswald-Insel Riems, Germany³

Received 5 February 2003/ Accepted 30 May 2003

Marek's disease (MD), a highly infectious disease caused by an oncogenic herpesvirus, is one of the few herpesvirus diseases against which live attenuated vaccines are used as the main strategy for control. We have constructed bacterial artificial chromosomes (BACs) of the CVI988 (Rispens) strain of the virus, the most widely used and effective vaccine against MD. Viruses derived from the BAC clones were stable after in vitro and in vivo passages and showed characteristics and growth kinetics similar to those of the parental virus. Molecular analysis of the individual BAC clones showed differences in the structure of the meq gene, indicating that the commercial vaccine contains virus populations with distinct genomic structures. We also demonstrate that, contrary to the published data, the sequence of the L-meq of the BAC clone did not show any frameshift. Virus stocks derived from one of the BAC clones (clone 10) induced 100 percent protection against infection by the virulent strain RB1B, indicating that BAC-derived viruses could be used with efficacies similar to those of the parental CVI988 vaccines. As a DNA vaccine, this BAC clone was also able to induce protection in 6 of 20 birds. Isolation of CVI988 virus from all of these six birds suggested that immunity against challenge was probably dependent on the reconstitution of the virus in vivo and that such viruses are also as immunogenic as the in vitro-grown BAC-derived or parental vaccine viruses. Although the reasons for the induction of protection only in a proportion of birds (33.3%) that received the DNA vaccine are not clear, this is most likely to be related to the suboptimal method of DNA delivery. The construction of the CVI988 BAC is a major step towards understanding the superior immunogenic features of CVI988 and provides the opportunity to exploit the power of BAC technology for generation of novel molecularly defined vaccines.

This article has been cited by other articles:

• Jarosinski, K. W., Margulis, N. G., Kamil, J. P., Spatz, S. J., Nair, V. K., Osterrieder, N. (2007). Horizontal Transmission of Marek's Disease Virus Requires US2, the UL13 Protein Kinase, and gC. J. Virol. 81: 10575-10587 [Abstract] [Full Text]  
• Spatz, S. J., Petherbridge, L., Zhao, Y., Nair, V. (2007). Comparative full-length sequence analysis of oncogenic and vaccine (Rispens) strains of Marek's disease virus. J. Gen. Virol. 88: 1080-1096 [Abstract] [Full Text]  
• Baigent, S. J., Petherbridge, L. J., Smith, L. P., Zhao, Y., Chesters, P. M., Nair, V. K. (2006). Herpesvirus of turkey reconstituted from bacterial artificial chromosome clones induces protection against Marek's disease.. J. Gen. Virol. 87: 769-776 [Abstract] [Full Text]  
• Gillet, L., Daix, V., Donofrio, G., Wagner, M., Koszinowski, U. H., China, B., Ackermann, M., Markine-Goriaynoff, N., Vanderplasschen, A. (2005). Development of bovine herpesvirus 4 as an expression vector using bacterial artificial chromosome cloning. J. Gen. Virol. 86: 907-917 [Abstract] [Full Text]  
• Petherbridge, L., Brown, A. C., Baigent, S. J., Howes, K., Sacco, M. A., Osterrieder, N., Nair, V. K. (2004). Oncogenicity of Virulent Marek's Disease Virus Cloned as Bacterial Artificial Chromosomes. J. Virol. 78: 13376-13380 [Abstract] [Full Text]