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Erratum: Chakraborty, P. et al. Macrophages from Susceptible and Resistant Chicken Lines have Different Transcriptomes following Marek’s Disease Virus Infection. Genes 2019, 10, 74
Article

Marek’s Disease Virus Telomeric Integration Profiles of Neoplastic Host Tissues Reveal Unbiased Chromosomal Selection and Loss of Cellular Diversity during Tumorigenesis

1
Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA
2
Department of Animal Science, University of California Davis, Davis, CA 95616, USA
3
Avian Disease and Oncology Laboratory, United States Department of Agriculture, Agricultural Research Service, East Lansing, MI 48823, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Antonio José Piantino Ferreira
Genes 2021, 12(10), 1630; https://doi.org/10.3390/genes12101630
Received: 19 September 2021 / Revised: 14 October 2021 / Accepted: 14 October 2021 / Published: 17 October 2021
(This article belongs to the Special Issue Genomics of Avian Viral Infections)
The avian α-herpesvirus known as Marek’s disease virus (MDV) linearly integrates its genomic DNA into host telomeres during infection. The resulting disease, Marek’s disease (MD), is characterized by virally-induced lymphomas with high mortality. The temporal dynamics of MDV-positive (MDV+) transformed cells and expansion of MD lymphomas remain targets for further understanding. It also remains to be determined whether specific host chromosomal sites of MDV telomere integration confer an advantage to MDV-transformed cells during tumorigenesis. We applied MDV-specific fluorescence in situ hybridization (MDV FISH) to investigate virus-host cytogenomic interactions within and among a total of 37 gonad lymphomas and neoplastic splenic samples in birds infected with virulent MDV. We also determined single-cell, chromosome-specific MDV integration profiles within and among transformed tissue samples, including multiple samples from the same bird. Most mitotically-dividing cells within neoplastic samples had the cytogenomic phenotype of ‘MDV telomere-integrated only’, and tissue-specific, temporal changes in phenotype frequencies were detected. Transformed cell populations composing gonad lymphomas exhibited significantly lower diversity, in terms of heterogeneity of MDV integration profiles, at the latest stages of tumorigenesis (>50 days post-infection (dpi)). We further report high interindividual and lower intraindividual variation in MDV integration profiles of lymphoma cells. There was no evidence of integration hotspots into a specific host chromosome(s). Collectively, our data suggests that very few transformed MDV+ T cell populations present earlier in MDV-induced lymphomas (32–50 dpi), survive, and expand to become the dominant clonal population in more advanced MD lymphomas (51–62 dpi) and establish metastatic lymphomas. View Full-Text
Keywords: herpesvirus; Marek’s disease virus (MDV); viral integration; chicken; avian genomics; FISH; telomere; lymphoma; viral oncogenesis; cytogenomics herpesvirus; Marek’s disease virus (MDV); viral integration; chicken; avian genomics; FISH; telomere; lymphoma; viral oncogenesis; cytogenomics
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MDPI and ACS Style

Glass, M.C.; Smith, J.M.; Cheng, H.H.; Delany, M.E. Marek’s Disease Virus Telomeric Integration Profiles of Neoplastic Host Tissues Reveal Unbiased Chromosomal Selection and Loss of Cellular Diversity during Tumorigenesis. Genes 2021, 12, 1630. https://doi.org/10.3390/genes12101630

AMA Style

Glass MC, Smith JM, Cheng HH, Delany ME. Marek’s Disease Virus Telomeric Integration Profiles of Neoplastic Host Tissues Reveal Unbiased Chromosomal Selection and Loss of Cellular Diversity during Tumorigenesis. Genes. 2021; 12(10):1630. https://doi.org/10.3390/genes12101630

Chicago/Turabian Style

Glass, Marla C., Justin M. Smith, Hans H. Cheng, and Mary E. Delany 2021. "Marek’s Disease Virus Telomeric Integration Profiles of Neoplastic Host Tissues Reveal Unbiased Chromosomal Selection and Loss of Cellular Diversity during Tumorigenesis" Genes 12, no. 10: 1630. https://doi.org/10.3390/genes12101630

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