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item Spatz, Stephen

Submitted to: American Veterinary Medical Association Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/21/2006
Publication Date: 7/14/2006
Citation: Spatz, S.J., Nair, V. 2006. Polymorphisms in the genomes of oncogenic and attenuated pathotypes of marek's disease virus serotype 1. American Veterinary Medical Association, July 20-22, 2006, Honolulu, HI. 2006 CDROM.

Interpretive Summary:

Technical Abstract: The complete DNA sequence of a bacterial artificial chromosome (BAC) clone of Marek’s disease virus serotype 1 (MDV-1) vaccine strain CVI988 was determined. The genome consists of 178,311 base pairs, with an overall G/C content of 44%, and represents the largest among the MDV strains sequenced so far. The sequence indicates that the overall gene organization of CVI988-BAC is identical to that of the virulent strains GA, Md5 and Md11. In examining open reading frames (ORFs) capable of encoding proteins with greater than 50 amino acids (aa) in the four sequenced strains of MDV, nine ORFs differ between avirulent and virulent pathotypes. A 177-base pair insertion was identified in the CVI988 gene encoding the oncogenic protein Meq, which is in agreement with research indicating that the Meq loci contribute to virulence. The overlapping ORFs, ORF 77.5 and ORF 77, encoding RLORF 6 and 23 kD protein, respectively also contained 177-bp insertions. Three ORFs are predicted to encode truncated proteins. One, designated 49.1, overlaps the gene encoding the large tegument protein UL36 (ORF 49) and encodes a severely truncated protein of 34 aa. The others truncated open reading frames, ORF5.5/ORF75.91 and ORF3/78, located in the repeat region of the CVI988 genomes and therefore diploid, encode a previously unidentified ORF of 52 a. a, and a truncated version of vIL8, respectively. Subtle genetic changes were identified in two ORFs (ORF 49 and ORF62) encoding essential tegument proteins UL36 and UL49, respectively. The large tegument protein (UL36) of CVI988 contains a stretch of amino acid residues dissimilar to those in other MDV homologues. The gene encoding the phosphoprotein UL49 of CVI988 contains a small deletion in a domain containing Threonine and Serine residues. Only one diploid ORF (ORF6.2/ORF75.6), present in the genomes of the three virulent pathotypes, is absent in the CVI988 genome. The significance of these genetic changes will require subsequent investigation. The CVI988-BAC sequence contains 14 copies of the previously characterized 132-bp repeat element found in the long repeat region. This and the fact that low passage avirulent strains of CVI988 contain only four copies of the 132-bp repeat element supports data indicating that expansion of the 132 bp repeat region, which accompanies attenuation, is not sufficient for attenuation.