Location: Endemic Poultry Viral Diseases Research
Title: Genome-wide analyses of an avian herpesvirus identify 10 loci associated with tumorigenicity and vaccine escapeAuthor
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ORTIGAS-VASQUEZ, ALEJANDRO - Pennsylvania State University |
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PANDEY, UTSAV - Pennsylvania State University |
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BELL, ANDREW - Pennsylvania State University |
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RENNER, DANIEL - Pennsylvania State University |
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JONES, MATTHEW - Pennsylvania State University |
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Cheng, Hans |
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Dunn, John |
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READ, ANDREW - Pennsylvania State University |
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BONI, MACIEJ - Temple University |
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KENNEDY, DAVID - Pennsylvania State University |
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SZPARA, MORIAH - Pennsylvania State University |
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Submitted to: Science Advances
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 5/28/2026 Publication Date: 7/29/2026 Citation: Ortigas-Vasquez, A., Pandey, U., Bell, A.S., Renner, D.W., Jones, M.J., Cheng, H.H., Dunn, J.R., Read, A.F., Boni, M.F., Kennedy, D.A., Szpara, M.L. 2026. Genome-wide analyses of an avian herpesvirus identify 10 loci associated with tumorigenicity and vaccine escape. Science Advances. Vol 12, Issue 31. https://doi.org/10.1126/sciadv.aee9024. DOI: https://doi.org/10.1126/sciadv.aee9024 Interpretive Summary: Marek's disease is a highly infectious disease of poultry that causes chickens to develop cancer. Correlating virus DNA sequence to the severity of disease is important for diagnosing and preventing disease, as well as understanding and predicting how the virus changes over time. Unlike previous studies that looked at partial sequences, this study evaluated the whole genome sequence of 65 strains of Marek's disease virus (MDV) that were previously characterized for level of disease severity. We found ten specific locations (loci) within the virus sequences that were strongly linked to the virus strength, with one repeating section having the strongest connection. This suggests that various parts of the DNA sequence explain the different ways the virus acts. The findings support virulence as a complex trait in MDV and conclude that several expected and unexpected sequence variants contribute to diversity of disease severity. Technical 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/or 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 the first genome-wide association study in MDV. In total, we identified 10 genome-wide significant loci associated with virulence. Notably, a tandem repeat variant resulting from two alternative versions of a 132-bp repeating motif was found to have the strongest association with virulence. Our findings support prior descriptions of virulence as a complex trait in MDV, while also highlighting the potential contribution of “non-traditional” genomic variants to the phenotypic diversity of herpesviruses. |
