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

Author
item Heidari, Mohammad
item HUEBNER, MARIANNE - MICHIGAN STATE UNIVERSITY
item KIREEV, DMITRY - NARVAC, MOSCOW, RUSSIA
item Silva, Robert

Submitted to: Virus Genes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/14/2008
Publication Date: 5/9/2008
Citation: Heidari, M., Huebner, M., Kireev, D., Silva, R.F. 2008. Transcriptional profiling of Marek's disease virus genes during cytolytic and latent infection. Virus Genes. 36:383-392.

Interpretive Summary: Marek's disease (MD), a virus induced cancer like disease of chickens, is considered as a major disease problem in commercial poultry. Vaccination has dramatically reduced the incidence of the disease, but very little is known about the viral products involved in the induction of disease. During the first 7 days of infection, MD virus (MDV) actively replicates in and cause lysis of the host B-lymphocytes, a phase called cytolytic infection. This cytolytic phase of infection is followed by a dormant phase of infection (latent infection) in another type of host cells called T-lymphocytes. In order to understand the process by which MDV cause the disease, we used a DNA-based technique, named microarrays to study MDV gene expression during cytolytic and latent phases of MDV infection. Our study revealed a significant differential pattern of MDV gene expression during the two phases of MDV infection, namely cytolytic and latent phases. The expression levels of more than 78 MDV genes were increased during the cytolytic infection when compared to latent infection (2-11 fold increase). There were only three viral genes that were expressed during both phases of infection, and at least 11 MDV genes that were not expressed during either stages of infection. The information should be helpful to scientists in academia and industry in understanding the molecular mechanism regulating MDV cytolytic and latent infections. The information should also be useful in development of more effective vaccines.

Technical 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 comprehensive MDV gene expression profiling using oligonucleotide-based Affymetrix GeneChip Chicken Genome Arrays. These arrays contain probes 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.