Location: Avian Disease and Oncology ResearchTitle: Characterizing in vivo stability and potential interactions of a UL5 helicase-primase mutation previously shown to reduce virulence and in vivo replication of Marek's disease virus
Submitted to: Virus Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/20/2015
Publication Date: 3/28/2015
Publication URL: http://handle.nal.usda.gov/10113/61006
Citation: Hildebrandt, E., Dunn, J.R., Cheng, H.H. 2015. Characterizing in vivo stability and potential interactions of a UL5 helicase-primase mutation previously shown to reduce virulence and in vivo replication of Marek's disease virus. Virus Research. 203(2015):1-3. doi: 10.1016/j.virusres.2015.03.011.
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, thus, understanding this process is critical for the development of improved vaccines. Previously we had shown that a specific mutation an MDV gene known as UL5 reduced disease incidence in attenuated strains by 90% or more. Additional studies indicated that this mutation affected the ability of the virus to replicate and did not revert to a more virulent form when backpassaged in live birds. These experiments expand our understanding of the complex nature of attenuation and virulence of this agronomically important virus, and should aid the poultry companies in making rationally-designed next generation MD vaccines.
Technical Abstract: The unpredictable yet recurrent emergence of more virulent field strains of Marek’s disease virus (MDV) in Marek’s disease (MD) vaccinated flocks of chickens has prompted concerns regarding the sustainability of MD vaccines. A single non-synonymous point mutation (I682R) within the UL5 helicase-primase unit was shown to reduce virulence by over 90%. Considering in vitro attenuation is commonly used to generate MD vaccines, this result prompted further characterization of this mutation, particularly to better understand the potential of point mutations for use in vaccine development. Incorporation of a second non-synonymous point mutation (UL46-Q117R; tegument) found at high frequencies in the same attenuated MDV as the UL5 mutation did not further reduce virulence compared to the single UL5 mutation alone. Furthermore, when the UL5-containing MDV was serially passed three times in vivo, the resulting viruses did not show increases in replication or virulence, and no revertant viruses could be detected. This suggests that point mutations that reduce fitness and in vivo replication may be more stable than initially anticipated, which may alleviate some concerns regarding rationally designed MD vaccines based upon point mutations.