Transcriptional profiling of Marek's disease virus genes during cytolytic and latent infection

Abstract

Marek's disease (MD), a lymphoproliferative disease of chicken is caused by a highly cell-associated alpha-herpesvirus, Marek's disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latent infection within CD4(+) T cells. The expression analysis of limited viral transcripts have revealed differences in gene expression pattern during cytolytic and latent phases of MDV infection. In this study, we conducted a global gene expression profiling of MDV using oligonucleotide-based Affymetrix GeneChip Chicken Genome Arrays. These arrays contain probe for more than 32,000 chicken transcripts and most of the known MDV genes and open reading frames. Two-week-old MD-susceptible chickens were inoculated with an oncogenic strain of MDV, and spleen samples were collected 5 and 15 days post inoculation (cytolytic and latent infection, respectively) for RNA isolation and microarray analysis. Array results displayed a significant differential pattern of viral transcriptome between the two phases of MDV infection. The expression levels of more than 78 MDV genes were increased during the cytolytic infection when compared to latent infection (2-11-fold increase). A 23-KD nuclear protein, meq oncoprotein, and R-LORF5 were among the few viral genes that were expressed during both phases of infection. In addition, there were at least 11 known and hypothetical genes that had no significant transcriptional activities during either stages of infection. These chicken genome arrays have considerable promise, as a valuable tool in understanding the molecular mechanism regulating MDV cytolytic and latent infection, and providing insights into the chicken gene expression pattern and associated biological pathways in response to different phases of viral pathogenesis.