Submitted to: Archives of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 23, 2007
Publication Date: June 8, 2007
Citation: Spatz, S.J., Silva, R.F. 2007. Sequence determination of variable regions within the genomes of Gallid herpesvirus-2 pathotypes. Archives of Virology. Available: http://www.springerlink.com/content/ku4064776312w861/. Interpretive Summary: The laboratories of Drs. Stephen J. Spatz (SEPRL) and Robert F. Silva (ADOL) have initiated a comparative genomics program to investigate genetic changes that exist in all 5 pathotypes of Gallid herpesvirus type 2 (GaHV-2). By determining the DNA sequences of various regions within the genomes of 13 strains we have discovered two genes that are likely involved in the severity of the disease as well as areas in the DNA that control the life cycle of the virus. This information will contribute to our understanding of the disease process of this virus and aid in our quest to develop new GaHV-2 vaccines.
Technical Abstract: Comparative genomic studies of attenuated and virulent strains of Gallid herpesvirus-2 (GaHV-2) have identified 6 regions of sequence variability. These regions include the open reading frames (ORFs) encoding UL36 and UL49 and regions devoid of large ORFs (132 bp repeats, a-like sequences and the junctions flanking the unique short region). Our data indicates that the carboxyl terminus of UL36 contains regions of heterogeneity that are unique to CVI988-derived attenuated strains. A deletion of the TKSERT domain and a glycine245 polymorphism in the UL49 proteins was also identified in these derivatives. Phylogenetic analyses of both UL36 and UL49 sequences indicate CVI988-derived strains partition differently than other attenuated strains (RM-1 and R2/23) indicating additional mutations contribute to attenuation. In very virulent and very virulent plus strains a single nucleotide polymorphism (SNP) was identified within the 132 bp tandem repeats. Within the junctions flanking the unique short region, these strains also contain deletions in sequences that are predicted to bind the transcription factor NF kappaB. In some attenuated strains, deletions were also identified in the latency associated transcript (LAT) promoters and adjacent regions encoding microRNAs. These results indicated that virulence is likely multi-factorial with contributions from both multiple genes and cis-acting sites.