|HILDEBRANDT, EVIN - Michigan State University|
|NIIKURA, MASAHIRO - Simon Fraser University|
Submitted to: Virology Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/23/2014
Publication Date: 12/3/2014
Publication URL: https://handle.nal.usda.gov/10113/60072
Citation: Hildebrandt, E., Dunn, J.R., Niikura, M., Cheng, H.H. 2014. Mutations within ICP4 acquired during in vitro attenuation do not alter virulence of recombinant Marek’s disease viruses in vivo. Virology Reports. 5:10-18.
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 primarily controlled by vaccines produced by attenuated virulent field strains. MDV ICP4 encodes an immediate early transcription factor and mutations in this gene arise in during viral attenuation. However, we find that these mutations are not sufficient to reduce disease incidence in chickens and, thus, are likely to enhance viral replication rates in cultured cells. This information helps in our understanding of viral replication and could lead to more effective and rationally-designed MD vaccines.
Technical Abstract: Marek's disease (MD) is a T-cell lymphoma of chickens caused by the oncogenic Marek's disease virus (MDV). MD is primarily controlled by live-attenuated vaccines generated by repeated in vitro serial passage. Previous efforts to characterize attenuated MDVs identified numerous mutations, particularly a convergence of high-frequency mutations around amino acids 60–63 within ICP4 (RS1), therefore, ICP4 was considered a candidate gene deserving further characterization. Recombinant MDVs were generated containing a single Q63H mutation or double Q63H + S1630P mutations. Despite the repetitive nature of mutations within ICP4, neither recombinant virus decreased virulence, although one mutant reduced in vivo replication and failed to transmit horizontally. Our results indicate that these mutations are insufficient to reduce disease incidence in infected birds, and suggest that variants in ICP4 do not directly alter virulence, but rather may enhance MDV replication rates in vitro, offering an explanation for the widespread occurrence of ICP4 mutations in a variety of attenuated herpesviruses.