Vaccination and host Marek's disease-resistance genotype significantly reduce oncogenic gallid alphaherpesvirus 2 telomere integration in host birds

Authors: MCPHERSON, MARLA - University Of California, Davis; Cheng, Hans; SMITH, JUSTIN - University Of California, Davis; DELANY, MARY - University Of California, Davis

Submitted to: Cytogenetics and Genome Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/14/2018
Publication Date: 12/21/2018
Citation: McPherson, M.C., Cheng, H.H., Smith, J.M., Delany, M.E. 2018. Vaccination and host Marek's disease-resistance genotype significantly reduce oncogenic gallid alphaherpesvirus 2 telomere integration in host birds. Cytogenetics and Genome Research. 156(4):204-214. https://doi.org/10.1159/000495174.
DOI: https://doi.org/10.1159/000495174

Interpretive Summary: Marek’s disease is one of the most serious infectious diseases of chickens and is characterized by the rapid onset of T cell lymphomas in susceptible birds. Understanding the interaction of the chicken genome with the Marek’s disease virus, the causative pathogen, is critical for future and more effective disease control. In this study, we determined that genetically resistant birds or ones that were vaccinated greatly reduced the ability of the virus to integrate, which is a prerequisite for tumor formation. This suggests that the lack of viral integration could be used as a marker to screen for more disease resistant birds or efficient vaccines. If this statement is true, then this would greatly aid in the reduction of disease and promote more healthier and economical poultry production.

Technical Abstract: 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.