Location: Avian Disease and Oncology ResearchTitle: The Mut UL5-I682R Marek’s disease virus with a single nucleotide mutation within the UL5 helicase-primase subunit gene not only reduces virulence, but also provides partial vaccinal protection against Marek's disease
Submitted to: Avian Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/13/2014
Publication Date: 11/13/2014
Publication URL: http://handle.nal.usda.gov/10113/60468
Citation: Hildebrandt, E., Dunn, J.R., Cheng, H.H. 2014. The Mut UL5-I682R Marek’s disease virus with a single nucleotide mutation within the UL5 helicase-primase subunit gene not only reduces virulence, but also provides partial vaccinal protection against Marek's disease. Avian Diseases. 59(1):94-97.
Interpretive Summary: Marek’s disease (MD) is a T cell lymphoma of chickens caused by the highly oncogenic Marek’s disease virus (MDV). MD is controlled by vaccines produced by attenuating virulent field strains. Previously we had shown that a specific mutation an MDV gene known as UL5 reduced disease incidence in attenuated strains by 90% or more. We compared this recombinant virus to other known commercial vaccines and determined while it could offer a protection against MD, it was not as effective as available vaccines. However, our results do support rationally-designed vaccines can be produced by study viral evolution.
Technical Abstract: Marek’s disease virus (MDV) is an oncogenic herpesvirus that afflicts chickens with the disease known as Marek’s disease (MD). This virus induces tumors, nerve lesions, immunosuppression, and death of affected birds. Vaccines are the primary control method for MD but, due to the periodic evolution of field strains, it is necessary to explore the development of new MD vaccines. MD vaccines are often attenuated MDV strains generated through serial passage in vitro. We previously used experimental evolution of MDV to provide a better understanding of the genetic basis of attenuation. During complete genome sequencing of evolved MDV populations, we identified a point mutation within the UL5 helicase-primase gene and created a UL5 recombinant virus that significantly reduced disease incidence by 89%–100%. To determine if experimental evolution also identifies mutations that provide protective qualities as potential vaccine candidates, we tested the UL5 recombinant virus as a vaccine and compared its protection to commercial herpesvirus of turkey (HVT) and bivalent (HVT + SB-1) vaccines. Both commercial vaccines resulted in higher protection against MD than did the UL5 recombinant virus, although the UL5 virus did provide protection against developing MD in 46%–70% of birds challenged. This indicates that a mutation within the UL5 helicase-primase gene not only reduces virulence but also confers protection against challenge with virulent MDV, providing support that not only can experimental evolution identify candidate mutations involved in attenuation but can also identify potential candidates for use in vaccine development.