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Title: Marek’s disease virus genomics

item Spatz, Stephen

Submitted to: International Marek's Disease Symposium Abstracts and Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 3/21/2008
Publication Date: 7/6/2008
Citation: Spatz, S.J. 2008. Marek’s disease virus genomics. International Marek's Disease Symposium Abstracts and Proceedings. 1(1):14.

Interpretive Summary:

Technical Abstract: Marek’s disease virus (MDV) is one of the most oncogenic herpesviruses known and induces a rapid onset T-cell lymphoma and demyelinating disease in chickens. It represents the first of three neoplastic diseases (including hepatocellular carcinoma: hepatitis B virus; and cervical carcinoma: human papilloma virus) for which an effective vaccine has been developed. The virus, gallid herpesvirus-2, is classified as a member of the genus Mardivirus in the Alphaherpesvirinae subfamily of Herpesviridae. The antigenically related Mardiviruses, meleagrid herpesvirus (MeHV-1) and non-oncogenic gallid herpesvirus 3 (GaHV-3) along with attenuated strains of GaHV-2 have been used since the early 1970s to control this disease. Despite nearly 40 years of vaccine development little is known of the genetic determinants responsible for attenuation. In order to gain a better perspective on the true variability of MDV strains and to catalogue the location and nature of the differences, 6 new complete genomes of varying virulence were sequenced and compared with those previously released in GenBank. Comparative genomics revealed that while the 178 kilobase genome of MDV is relatively stable genetically, it does possess some degree of variability. Most of the variability clusters outside the unique long (UL) and unique short (US) regions in three reiteration regions, the 60 base pair repeats and telomeric sequences within the a-like sequence and the 132 bp repeats within the repeat long (RL) region. Variable intragenic and intergenic homopolymers were found throughout the MDV genomes. The highest number (34) was present within the RL regions. Analysis of single nucleotide polymorphisms and gross mutations among attenuated strains (e.g. CVI988 and CU-2) and non-attenuated strains has identified 5 genes (Meq, RLORF4, RLORF12, vIL8 and vLip) likely to play a role in virulence. Relative to the vaccine strain CVI988, 109 and 99 non-synonymous substitutions were found in the open reading frames (ORFs) of virulent strains Md11 and Md5, respectively. Only 24 substitutions were common to both Md11 and Md5. In comparing the mildly virulent strain CU-2 to CVI988, a total of 15 single nucleotide polymorphisms (SNPs) common to both CU-2 and CVI988, and not occurring in virulent strains, were identified. It is largely suspected that SNPs shared with CVI988, along with mutations in five genes are responsible for attenuation.