Understanding the First Effective Vaccination Against a Cancer: Interactions of Marek’s Disease Virus and Vaccines with the Host Genome

Marek’s Disease Virus (MDV) is a chicken alphaherpesvirus that causes paralysis, chronic wasting, blindness, and fatal lymphoma development, collectively known as Marek’s disease (MD), within its natural host, chicken (Gallus gallus). Virulent MDV strains are known to integrate into the host telomeres during disease pathogenesis. Most mitotically-dividing cells within primary MD-lymphomas contain solely telomere-integrated MDV. MD vaccinations are administered to prevent fatal tumor development after MDV infection, establishing these vaccines as the first effective against an oncogenic virus. The genomic interactions of the vaccines with their host and the precise mechanism of the anti-tumor effect of vaccination are not well understood. We examined whether MD vaccines are capable of integration into the host genome by cytogenetic analysis during the first 3 weeks after inoculation. In this study, we established that MD vaccines are indeed capable of integrating into host telomeres; however the vaccines don’t establish the MDV-host genomic profile observed in latent and transformed cell types. Our results highlight that the establishment of a viral stage known as latency, and the accompanying viral phenotype, during early infection may be a critical precursor to MDV-induced tumorigenesis. Our current aim is to investigate changes in the interactions of virulent MDV with the host DNA in MD-susceptible versus -resistant birds.

We appreciate support from the National Institute of Food and Agriculture, U.S. Department of Agriculture grant 2005-35205-16679, National Research Support Program-8, and Multi-State Research Projects NC-1170 and NE-1334.