Lorf9 deletion significantly eliminated lymphoid organ atrophy induced by meq-deleted very virulent Marek's disease virus.

• Generation a double deletion mutant Marek's disease virus absence of both meq and lorf9 genes. • Double deletion mutant Marek's disease virus has similar growth characteristics with parental virus in vitro. • Double deletion mutant Marek's disease virus significantly reduced replication in vivo. • Double deletion of meq and lorf9 genes overcome lymphoid organ atrophy induced by meq-deletion Marek's disease virus. • Double deletion mutant Marek's disease virus is fully attenuated. Marek's disease virus (MDV) is a highly contagious alphaherpesvirus that causes rapid onset of T cell lymphomas in chickens. MDV continues to break through vaccinal immunity due to the emergence of highly virulent field strains. Earlier studies revealed that deletion of the meq gene from MDV results in attenuated vaccines that protect against disease when chickens are infected with highly virulent strains. However, meq -deleted viruses still retain the ability to induce lymphoid organ atrophy, which raises safety concerns. In an earlier study, we found that deletion of lorf9 counteracts this lymphoid organ atrophy. Here, we describe the generation of a double deletion mutant virus lacking virus-encoded meq and lorf9. In vitro studies revealed that during replication, the mutant virus had kinetic characteristics similar to the parental virus; however, in vivo the replication capability was significantly reduced. Results of animal studies revealed no obvious MDV-specific symptoms and lesions. Importantly, the double deletion mutant virus lost the capacity to induce lymphoid organ atrophy, which has been the main obstacle during development of a good vaccine candidate. [ABSTRACT FROM AUTHOR]