The role of Marek's disease virus MEQ gene products on MDV pathogenicity and oncogenicity
Date
2011
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Marek's Disease (MD) is a lymphoproliferative disease of chickens caused by Marek's disease virus (MDV). MDV induces rapid-onset T-cell lymphomas in chickens and T-cell transformation requires expression of a viral protein called Meq, (Marek's EcoRI-Q-encoded protein). Previously, we reported that changes in the coding sequence of Meq correlated with increased virulence. Our present study had three aims. The first aim was to determine the expression pattern of Meq proteins in vivo and to characterize their functions. Our data indicated that full-length Meq was expressed during lytic infection in vivo, with a peak in expression at three weeks. Meq splice-variant proteins were first observed at this time point, and these were also observed in MDV-induced tumors, and MDV-transformed cell lines. All Meq proteins induced cell proliferation, bound to the MDV genome at Meq, ICP4, and pp38/pp14 promoters, but only full length Meq functions as a transcriptional activator. The second research aim was to examine the replication and pathogenesis of an RB1B-based double Meq knock-out virus. Our results suggest that the deletion of meq had no effect on its lytic replication in cell culture, but markedly attenuated the virus (RB1BMeqKO) in vivo. Unlike an MD5-based Meq deletion virus (MD5?Meq), RB1BMeq KO replicated to a very low level and caused no thymic atrophy. As a third research aim, we examined the effect of three Meq point mutations on changes in pathogenicity using an in vivo-selected recombinant virus, rMDV-1137. rMDV-1137 had the RB1B form of Meq expressed within the context of the MD5 genome. rMDV-1137 resembled both RB1B and MD5 in vivo, in terms of replication, transmission, and pathogenicity. rMDV-1137 induced tumors from which we were able to establish cell lines similar to RB1B- , but not from MD5-induced lymphomas. Our data suggests that changes in meq sequence mediate subtle changes in oncogenicity and that the background strain also affects MDV pathogenicity and oncogenicity.