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Title: Comparative sequence analysis of a highly oncogenic but horizontal spread-defective clone of Marek's disease virus

item Spatz, Stephen

Submitted to: Virus Genes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/18/2007
Publication Date: 8/25/2007
Citation: Spatz, S.J., Zhao, Y., Petherbridge, L., Smith, L., Baigent, S., Nair, V. 2007. Comparative sequence analysis of a highly oncogenic but horizontal spread-defective clone of Marek's disease virus. Virus Genes. 35:753-766.

Interpretive Summary: The laboratory of Stephen Spatz and collaboration with Venugopal Nair from the Institute for Animal Health, Compton, UK has determined the DNA sequence of the RB1B strain of Marek's virus. This strain is particularly interesting due to its biological properties. It is highly oncogenic but unable to spread from infected bird to other susceptible bird. In comparison to other shedding competent viruses, the RB1B strain has mutations affecting cell signalling and receptor binding. This is of value in understanding the mechanisms involved in shedding which will allow scientists the ability to design next generation vaccines.

Technical Abstract: Marek’s disease virus (MDV) is a cell-associated alphaherpesvirus that induces rapid-onset T-cell lymphomas in poultry. MDV isolates vary greatly in pathogenicity. While some of the strains such as CVI988 are non-pathogenic and are used as vaccines, others such as RB1B are highly oncogenic. Comparison of the genome sequences of phenotypically different strains could help to identify molecular determinants of pathogenicity. We have previously reported the construction of a bacterial artificial chromosome (BAC) clone of RB1B. MDV reconstituted from RB1B-BAC DNA showed similar in vitro and in vivo replication kinetics and were equally oncogenic as the parent wild type virus. However, the BAC-derived MDV was unable to spread horizontally to sentinel birds although viral DNA could be detected in their feather follicles. Complete nucleotide sequence of this horizontal spread-negative virus was determined and comparisons with the sequence of transmission-competent Md5 strain demonstrated frameshift mutations in the ICP0-like protein RLORF1, protein kinase (UL13) and glycoproteins C (UL44) and D (US6) as well as six novel MDV ORFs. Of particular interest were the mutations within the UL13 protein kinase and glycoprotein C genes in light of research indicating essential roles for these two proteins in skin infectivity of the related cell-associated varicella-zoster virus.