Vaccination and Host Marek's Disease-Resistance Genotype Significantly Reduce Oncogenic &lt;b&gt;&lt;i&gt;Gallid alphaherpesvirus 2&lt;/i&gt;&lt;/b&gt; Telomere Integration in Host Birds

McPherson, Marla C.; Cheng, Hans H.; Smith, Justin M.; Delany, Mary E.

doi:10.1159/000495174

Cited by 4 publications

(5 citation statements)

References 60 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The telomere-integrated only phenotype indicates a host cell that is primed for or has undergone MDV-induced oncogenic transformation. In this and prior studies, most mitotically-dividing cells within neoplastic tissues had the MDV telomere-integrated only phenotype [7,62], further supporting the link between this integrated-MDV phenotype and infected T cell transformation. The complete absence of the MDV chromosome-associated only phenotype, characterized by MDV DNA episomes tightly associated with host chromosomes, within the neoplastic splenic and gonad tissues was notable and suggests that there were little to no dividing cells with lytically replicating MDV within these neoplastic tissue samples.…”

Section: Gonad Lymphomassupporting

confidence: 78%

“…We observed three of four previously described MDV phenotypes [7,8,31,62] in the samples: specifically, the MDV null phenotype (no virus), the MDV chromosomeassociated/telomere-integrated phenotype and the telomere-integrated-only MDV phenotype (Figure 2a). The MDV chromosome-associated-only phenotype was not observed in either sample type.…”

Section: Data Visualization and Statistical Analysismentioning

confidence: 67%

“…Study part I. Thirty-six samples (15 gonad lymphomas and 21 splenic samples) from 27 birds were evaluated in terms of their MDV cellular phenotypes and MDV-integration profiles within and across host nuclei [7,31,62]. MDV integration profiles indicate MDV integration events into host bird individual macrochromosomes (GGA 1-4, Z and W) as well as into intermediate-sized chromosomes and microchromosomes, together as a single category.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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

Glass

Smith

Cheng

et al. 2021

Genes

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Gonad Lymphomassupporting

confidence: 78%

Section: Data Visualization and Statistical Analysismentioning

confidence: 67%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

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

Glass

Smith

Cheng

et al. 2021

Genes

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thus, the presence/enrichment of these TTA-looped G4 sequences close to the viral genome extremities, their requirement for efficient virus integration [55], and the observation that G4 ligands can interfere with virus integration [54] point to the role played by these sequences in this crucial process that ensures virus maintenance in latently infected human cells. This potential for telomere integration is not exclusive to human herpesviruses, since it has been also described in the oncogenic Marek’s disease alpha-herpesvirus, which infects chicken lymphocytes [56]. This particular virus also carries TTA-looped G4 repeats at the ends of its linear genome, and its pathogenicity partially depends on the efficiency of telomere integration [56].…”

Section: Resultsmentioning

confidence: 99%

“…This potential for telomere integration is not exclusive to human herpesviruses, since it has been also described in the oncogenic Marek’s disease alpha-herpesvirus, which infects chicken lymphocytes [56]. This particular virus also carries TTA-looped G4 repeats at the ends of its linear genome, and its pathogenicity partially depends on the efficiency of telomere integration [56]. Altogether, these observations suggest that the broad presence of viral TTA-looped quadruplex sequences might be functionally and evolutionary related to the telomere biology of the hosts.…”

Section: Resultsmentioning

confidence: 99%

Relationship Between G-Quadruplex Sequence Composition in Viruses and Their Hosts

2019

View full text Add to dashboard Cite

A subset of guanine-rich nucleic acid sequences has the potential to fold into G-quadruplex (G4) secondary structures, which are functionally important for several biological processes, including genome stability and regulation of gene expression. Putative quadruplex sequences (PQSs) G3+N1–7G3+N1–7G3+N1–7G3+ are widely found in eukaryotic and prokaryotic genomes, but the base composition of the N1-7 loops is biased across species. Since the viruses partially hijack their hosts’ cellular machinery for proliferation, we examined the PQS motif size, loop length, and nucleotide compositions of 7370 viral genome assemblies and compared viral and host PQS motifs. We studied seven viral taxa infecting five distant eukaryotic hosts and created a resource providing a comprehensive view of the viral quadruplex motifs. Overall, short-looped PQSs are predominant and with a similar composition across viral taxonomic groups, albeit subtle trends emerge upon classification by hosts. Specifically, there is a higher frequency of pyrimidine loops in viruses infecting animals irrespective of the viruses’ genome type. This observation is confirmed by an in-depth analysis of the Herpesviridae family of viruses, which showed a distinctive accumulation of thermally stable C-looped quadruplexes in viruses infecting high-order vertebrates. The occurrence of viral C-looped G4s, which carry binding sites for host transcription factors, as well as the high prevalence of viral TTA-looped G4s, which are identical to vertebrate telomeric motifs, provide concrete examples of how PQSs may help viruses impinge upon, and benefit from, host functions. More generally, these observations suggest a co-evolution of virus and host PQSs, thus underscoring the potential functional significance of G4s.

show abstract

Tumors of the avian immune system

Nair

2022

Avian Immunology

View full text Add to dashboard Cite

Vaccination and Host Marek's Disease-Resistance Genotype Significantly Reduce Oncogenic <b><i>Gallid alphaherpesvirus 2</i></b> Telomere Integration in Host Birds

Cited by 4 publications

References 60 publications

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

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

Relationship Between G-Quadruplex Sequence Composition in Viruses and Their Hosts

Tumors of the avian immune system

Contact Info

Product

Resources

About