LORF9 of Marek’s disease virus is involved in the early cytolytic replication of B lymphocytes and can act as a target for gene deletion vaccine development

Abstract

ABSTRACT Marek’s disease (MD) is a poultry disease characterized by severe immunosuppression and the development of T cell lymphomas caused by Marek’s disease virus (MDV). Our study focuses on the role of the viral LORF9 gene in MD pathogenesis and vaccine development. We found that a LORF9 gene deletion mutant (Md5BAC Δ LORF9 ) showed significantly reduced pathogenicity compared with the parental strain. The LORF9 gene is essential for the early cytolytic infection in B cells. Interestingly, Md5BAC Δ LORF9 provided adequate immunological protection against very virulent MDV challenge and induced a distinct host immune response compared with the CVI988/Rispens vaccine strain. Transcriptome analysis revealed that the deletion of LORF9 led to a significantly different expression of innate immunity-associated genes. Overall, our study provides insights into the role of LORF9 in MD pathogenesis and highlights its importance in MDV gene deletion vaccine development. IMPORTANCE Marek’s disease virus (MDV) is a highly infectious and oncogenic virus that can induce severe T cell lymphomas in chickens. MDV encodes more than 100 genes, most of which have unknown functions. This work indicated that the LORF9 gene is necessary for MDV early cytolytic replication in B lymphocytes. In addition, we have found that the LORF9 deletion mutant has a comparative immunological protective effect with CVI988/Rispens vaccine strain against very virulent MDV challenge. This is a significant discovery that LORF9 can be exploited as a possible target for the development of an MDV gene deletion vaccine.