Location: Avian Disease and Oncology ResearchTitle: Marek’s disease herpesvirus vaccines integrate into chicken host chromosomes yet lack a virus-host phenotype associated with oncogenic transformation
|MCPHERSON, MARLA - University Of California|
|DELANY, MARY - University Of California|
Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/23/2016
Publication Date: 10/5/2016
Publication URL: http://handle.nal.usda.gov/10113/63281
Citation: McPherson, M.C., Cheng, H.H., Delany, M.E. 2016. Marek’s disease herpesvirus vaccines integrate into chicken host chromosomes yet lack a virus-host phenotype associated with oncogenic transformation. Vaccine. 34(46):5554-5561. doi:10.1016/j.vaccine.2016.09.051.
Interpretive Summary: Vaccines are the primary method for controlling Marek’s disease (MD), a lymphoproliferative disease of chickens caused by an highly oncogenic herpesvirus. Despite 40+ years of widespread vaccination in commercial poultry flocks, the mechanisms of immunity is not known. In this effort, the viral integration profiles of commonly used MD vaccines were examined and found to integrate near chicken host telomeres very early after infection, which is similar to virulent viruses. This results proves that viral integration is not sufficient to cause neoplastic transformation in chickens, and has implications on how to improve vaccinal efficacy.
Technical Abstract: Marek's disease (MD) is a lymphotrophic and oncogenic disease of chickens that can lead to death in susceptible and unimmunized host birds. The causative pathogen, Marek's disease virus (MDV), a highly oncogenic alphaherpesvirus, integrates into host genome near the telomeres during viral latency and is thought to be necessary for host cellular transformation. MD occurrence is presently controlled across the globe by biosecurity, selective breeding for enhanced MD genetic resistance, and widespread vaccination of flocks using attenuated MDV or related viruses. Despite over 40 years of usage, the specific mechanism(s) of MD vaccine-related immunity and the anti-tumor effect of vaccination are not known. We investigated the cytogenomic interactions of commonly used MD vaccine strains of all three serotypes (HVT, SB-1, and Rispens) with the host and sought to determine if all were capable of host genome integration and if so, then where? Here we present the chromosomal association and integration profiles of the three vaccine strains, established for the first time in MD research. Our cytogenetic data provide evidence that the all MD vaccine strains tested can integrate at the chicken host telomeres as early as 1 day after vaccination in lymphoid tissue similar to the oncogenic strains, but do not establish the specific, transformation-associated viral phenotype observed for oncogenic viruses during early infection. Our results collectively provide an updated model of MD vaccine trends in the spleen of host birds and may lead to an improved understanding of vaccinal immunity and mechanisms. Based on these results, physical integration of the MDV genome into host telomeres along with a cease of viral replication appears to have a cooperative implication in MDV’s ability to induce oncogenic transformation.