Submitted to: Viral Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/22/2010
Publication Date: 6/30/2010
Citation: Heidari, M., Sarson, A.J., Huebner, M., Sharif, S., Kireev, D., Zhou, H. 2010. Marek's Disease Virus-Induced Immunosuppression: Array Analysis of Chicken Immune Response Gene Expression Profiling. Viral Immunology. 23(3):309-319. Interpretive Summary: Marek’s disease (MD), an economically important virus-induced cancer-like disease of chickens, is caused by MD virus (MDV). MDV is a herpesvirus that interferes with the normal function of immunity and avoids antiviral immune responses in affected chickens. We conducted a study known as comprehensive host-gene expression analysis using a technology that allows the determination of expression levels of several host genes (level of immune proteins coded for by the gene) under different physiological conditions. The results showed significant differences in gene expression between MD infected and uninfected chickens. Many of the genes that were expressed at low levels as a result of MDV infection, play a critical role in an effective antiviral immunity, suggesting MDV interference with normal chicken immune response. This information is important as it provides insights into the molecular mechanism of MDV virulence and its interference with the normal function of the immune system. The information also serves as the groundwork for future investigations that are aimed at enhancing the immune response to MD and consequently better control of this important disease of chickens.
Technical Abstract: Marek’s disease (MD) is a lymphoproliferative disease of chickens induced by a highly cell-associated oncogenic alpha-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latency infection within CD4+ T cells. Host-virus interaction, immune responses to infection, and transcriptional profiling of chicken gene expression in MD is poorly understood. In this study, we conducted a global host gene expression analysis in the splenocytes of MDV-infected chickens 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 infection (dpi) for RNA isolation and microarray analysis. Array results displayed a significant differential pattern of immune response transcriptome between the two phases of MDV infection. The expression levels of more than 23 immune response and related genes were down regulated, while the expression levels of at least 62 genes were increased at 5 dpi (cytolytic infection) when compared to age-matched control birds. In comparison, out of 83 immune response and related genes, 76 genes were down regulated with only 8 genes having higher expression levels at 15 dpi (latency infection). Cytokines, chemokines, MHC molecules and related receptors, and adhesion molecules were among the many MDV-induced down-regulated genes that are critical for an effective antiviral immune response. In addition, several apoptosis-associated genes were decreased in expression during latent infection, suggesting an MDV-induced blocking of initiation or progression of programmed cell death processes. These chicken arrays are valuable tools in understanding the molecular mechanism of viral pathogenesis and chicken gene expression pattern and associated biological pathways in response to MDV infection.