Genome-wide analyses of an avian herpesvirus identify 10 loci associated with tumorigenicity and vaccine escape

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Abstract
Comparative genomic studies of Marek’s disease virus (MDV) conducted in the past two decades have proven powerful for identifying genomic loci driving historical shifts in virulence. However, past efforts were limited to comparing a few strains at a time, lacked access to certain regions of the MDV genome, and were restricted in their ability to characterize viral phenotypes. To address these limitations, we performed whole-genome sequencing on a collection of 65 MDV strains previously characterized using a standardized phenotyping assay. In addition to phylogenetic and recombination analyses, this approach enabled us to perform a genome-wide association study of virulence for this pathogen. In total, we identified 10 genome-wide significant loci associated with virulence, including a tandem repeat variant resulting from two alternative versions of a 132-bp repeating motif. Our findings support prior descriptions of virulence as a complex trait in MDV, and highlight the potential contribution of repeat-based and intergenic variants to the phenotypic diversity of herpesviruses.
Funding Information
  • National Science Foundation (R01GM105244)
  • National Science Foundation (R01GM140459)
  • National Science Foundation (R01GM140459)
  • Pennsylvania Department of Health (CURE funds)

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