scholarly journals Vaccination and Host Marek's Disease-Resistance Genotype Significantly Reduce Oncogenic Gallid alphaherpesvirus 2 Telomere Integration in Host Birds

2018 ◽  
Vol 156 (4) ◽  
pp. 204-214 ◽  
Author(s):  
Marla C. McPherson ◽  
Hans H. Cheng ◽  
Justin M. Smith ◽  
Mary E. Delany
Keyword(s):  
Temporal Dynamics ◽  
Protective Efficacy ◽  
Marek's Disease ◽  
Host Genome ◽  
Marek’S Disease ◽  
Susceptible Genotype ◽  
Host Genotype ◽  
Host Genetics ◽  
Genome Interactions ◽  
Virus Integration

Marek's disease (MD) is an infectious disease characterized by lymphomas and high mortality in susceptible chickens. The causative and ubiquitous alpha-herpesvirus known as MD virus (MDV) integrates into host telomeres during early infection through latency, known to be an important phase for oncogenic transformation. Herein, we sought to determine the influence of vaccination and host genetics on the temporal dynamics of MDV-host genome interactions. We studied integration profiles using 2 MD vaccines that vary in protective efficacy in 2 genetic lines that differ in MD resistance/susceptibility. Virus integration of both oncogenic MDV and vaccine strains was observed in both MD susceptible and resistant birds, however, the lines differed in their dynamic telomere-integration profiles. Notably, the resistant host genotype exhibited a smaller percentage of replicating cells with the virus telomere-integrated only phenotype as compared to the susceptible genotype. Vaccination with Rispens, the most protective MD vaccine, also reduced the establishment of the virus telomere-integrated only phenotype, suggesting a significant role of the phenotype in MD lymphoma development. The effect of Rispens vaccination was most dramatic in the susceptible genotype. These results suggest important connections between vaccinal immunity, MDV telomere integration, virus-induced oncogenesis, and virus-host genome interactions in the context of host genetics and disease susceptibility.

Host genetic resistance to Marek's disease sustains protective efficacy of herpesvirus of turkey in both experimental and commercial lines of chickens

Vaccine ◽  
2014 ◽  
Vol 32 (16) ◽  
pp. 1820-1827 ◽  
Author(s):  
Shuang Chang ◽  
Qingmei Xie ◽  
John R. Dunn ◽  
Catherine W. Ernst ◽  
Jiuzhou Song ◽  
...  
Keyword(s):  
Protective Efficacy ◽  
Genetic Resistance ◽  
Marek's Disease ◽  
Marek’S Disease ◽  
Host Genetic

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

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1630
Author(s):  
Marla C. Glass ◽  
Justin M. Smith ◽  
Hans H. Cheng ◽  
Mary E. Delany
Keyword(s):  
Disease Virus ◽  
Temporal Dynamics ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Transformed Cells ◽  
Cell Populations ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Host Chromosome ◽  
Specific Host

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.

scholarly journals Resistance to Marek's Disease Herpesvirus-induced Lymphoma is Multiphasic and Dependent on Host Genotype

2001 ◽  
Vol 38 (2) ◽  
pp. 129-142 ◽  
Author(s):  
S. C. Burgess ◽  
B. H. Basaran ◽  
T. F. Davison
Keyword(s):  
Rank Order ◽  
Clinical Signs ◽  
Antigen Expression ◽  
Marek's Disease ◽  
Transformed Cells ◽  
Marek’S Disease ◽  
Host Genotype ◽  
Time Line ◽  
Cell Numbers ◽  
Infiltrating Cells

Genotype-dependent differences in Marek's disease (MD) susceptibility were identified using 14-day-old line N and 61 (resistant) and 15I and 72 (susceptible) inbred chickens infected with HPRS-16 MD virus (MDV). All line 72 chickens developed progressive MD. Line 15I had fluctuating MD-specific clinical signs and individuals recovered. A novel histologic scoring system enabled indices to be calculated for lymphocyte infiltration into nonlymphoid organs. All genotypes had increased mean lesion scores (MLSs) and mean total lesion scores after MDV infection. These differed quantitatively and qualitatively between the genotypes. Lines 61 and 72 had a similar MLS distribution in the cytolytic phase, although scores were greater in line 72. At the time lymphomas were visible in line 72, histologic lesions in line 61 were regressing. AV37+ cells were present in similar numbers in all genotypes in the cytolytic phase, suggesting that neoplastically transformed cells were present in all genotypes regardless of MD susceptibility. After the cytolytic phase, AV37+ cell numbers increased in lines 72 and 15I but decreased in lines 61 and N. In the cytolytic and latent phases, in all genotypes, most infiltrating cells were CD4+. After this time, line 72 and 15I lesions increased in size and most cells were CD4+; line 61 and N lesions decreased in size and most cells were CD8+. In all genotypes, AV37 immunostaining was weak in lesions with many CD8+ cells, suggesting that AV37 antigen expression or AV37+ cells were controlled by CD8+ cells. The rank order, determined by clinical signs and pathology, for MD susceptibility (highest to lowest) was 72 > 15I > 61 > N.

Sign in / Sign up

Export Citation Format

Share Document