Submitted to: Archives of Virology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/22/2005
Publication Date: 2/20/2006
Citation: Niikura, M., Dodgson, J.B., Cheng, H.H. 2006. Stability of Marek's disease virus 132bp repeats during serial in vitro passages. Archives of Virology. 151:1431-1438. Interpretive Summary: Marek’s disease (MD) is an economically-important disease of chickens caused by a pathogenic virus known as the Marek’s disease virus (MDV). Currently, vaccines have controlled the problem but new emerging viral strains that vaccines cannot control are being encountered more frequently. The mechanism by which MDV strain becomes more virulent is not known. In this paper, we show that expansion of the 132 bp repeat region, which is associated with viral attenuation, is not due to instability of this region. This information enhances our understanding of the emergence of more virulent MDV strains, and provides basic scientific information for improved control of MD.
Technical Abstract: The Marek’s disease virus (MDV) genome contains 2 sets of 132 bp tandem repeat sequences. An increase in 132 bp repeat units has been associated with attenuation of oncogenicity during in vitro passage. By cloning entire genomes, we demonstrated that the copy number of 132 bp repeats can differ within an individual MDV genome. The stability of the 132 bp repeats during cell passage depended on the initial copy number. When both sets of repeats contained 2 copies, the copy number remained stable, while if even 1 set of repeats contained 6 copies, repeat expansion occurred relatively quickly. This expansion did not affect the in vitro growth curve. However, when MDV clones with low and high copy numbers were passed together, genomes with expanded repeats rapidly predominated, mimicking the behavior of naturally-occurring MDV. Our results suggest that the preponderance of high-copy repeats after passage reflects intracellular copy number within individual infected cells rather than an influence on the number of infected cells.