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 are 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 22 immune-response and related genes were downregulated, while the expression levels of at least 58 genes were increased at 5 dpi (cytolytic infection), compared to age-matched control birds. In comparison, out of 73 immune-response and related genes, 67 genes were downregulated, with only 6 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 downregulated 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 mechanisms behind viral pathogenesis and chicken gene expression patterns, and associated biological pathways in response to MDV infection.
Toll-like receptors (TLRs) participate in detecting microbial pattern molecules for activation of the host immune response. We investigated possible roles of TLRs in the chicken response to Clostridium perfringens infection by examining the expression of TLR genes and other genes involved in TLR-mediated signaling within the spleens and ilea of C. perfringens-challenged broilers. Upregulation of a tumor necrosis factor alphainducing factor homolog in challenged chickens compared to naïve chickens was observed, regardless of the incidence of necrotic enteritis. In addition, the members of the TLR2 subfamily were found to be most strongly involved in the host response to C. perfringens challenge, although the expression of TLR4 and TLR7 was also upregulated in spleen tissues. While the combination of TLR1.2, TLR2.1, and TLR15 appeared to play a major role in the splenic response, the expression of TLR2.2 and TLR1.1 was positively correlated to the expression of adaptor molecules MyD88, TRAF6, TRIF, and receptor interacting protein 1 in the ileal tissues, demonstrating a dynamic spatial and temporal innate host response to C. perfringens.
Marek's disease virus (MDV) is a cell-associated oncogenic herpesvirus that targets B cells and T cells, inducing lymphoid tumours in chickens. Genetic resistance to Marek's disease (MD) is regulated in a polygenic fashion. In this study, we sought to compare the gene expression profiles following infection of birds that are genetically resistant or susceptible to MD (with the B21 and B19 haplotypes respectively at the MHC locus), including comparisons to uninfected controls. On days 4, 7, 14 and 21 post-infection, gene expression profiles in spleen tissue were obtained using a chicken immune-specific microarray. A number of genes showed significant (P
This study was aimed at investigating the genes that control host responses to Marek's disease virus (MDV). Spleen tissues from infected and age-matched uninfected control chickens were examined 4, 7, 14, and 21 d postinfection for gene expression differences, using both microarray and quantitative real-time polymerase chain reaction (PCR) methodologies. Up to 51% of genes assayed during microarray analysis showed a significant change (p < or = 0.05) in expression after MDV infection, of which cell surface molecules, transcription and signal transduction molecules, housekeeping and metabolism mediators, and cytokines and cytokine receptors were most commonly differentially expressed. Setting a fold change threshold (> or =2), 14 of 84 genes showed differential expression over time. In addition, some genes showed differential expression at more than one time point. For example, the granzyme-A homolog gene remained upregulated in infected chickens, with fold changes of 7.98, 13.91, and 9.07 at 7, 14, and 21 d postinfection, respectively. Other genes that were differentially expressed at more than one time point were invariant chain, IgM, and CD3. Quantitative real-time PCR analysis was used to validate microarray results for a subset of genes showing a :2-fold change in expression. Expression of all but one gene (CD28) was confirmed. Identification of genetic mechanisms initiated by in vivo infection with MDV expands the current understanding of immune response to the virus in addition to host response elements associated with viral pathogenesis.
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