Gene expression analysis of host spleen responses to Marek's disease virus infection at late tumor transformation phase

Abstract

<p>Marek's disease is a viral neoplastic disease of chickens caused by Marek's disease virus (MDV). Gene expression patterns have been investigated at different MDV infection stages, but there is limited research about the late tumor transformation phase. In this experiment, 44K Agilent chicken genome-wide expression microarrays were used to profile differential expression in tumorous spleens (TS) from severely morbid chickens and apparently normal spleens from survivors (SS) after MDV infection and expression in noninfected spleens (NS) from controls. There were 4,317 differentially expressed (DE) genes in TS versus NS. However, no DE genes were detected in SS versus NS, suggesting that maintenance of, or return to, homeostasis of gene activity in survivor spleens. Downregulated genes in tumorous spleens mainly enriched in the cytokine-cytokine receptor interaction pathway, and commonly investigated genes in Marek's disease study, <em>IL6, IL18, IFNA</em>, and <em>IFNG</em> were nondifferentially expressed, which indicates host inflammatory response was impaired. The <em>IL10</em> and <em>TNFRSF8</em> genes were upregulated in tumorous spleens. We speculated that <em>IL10</em> might be exploited by MDV to escape from host immune surveillance, as reported for Epstein-Barr virus, which stimulated T cells secreting IL10 to subvert immune response. Previous study reported that transcription from <em>TNFRSF8</em> promoter could be enhanced by MDV oncogene <em>Meq</em>. In this study, the increased expression of <em>TNFRSF8</em> indicated interaction between MDV and TNFRSF8, which might facilitate pathogenesis and tumor transformation. The expression of many members in IGF system was changed in tumorous compared with noninfected spleens. The downregulation of <em>IGFBP7</em> was considered to be associated with MD lymphoma transformation. Gene expression change of multiple regulatory pathways indicated their involvements in facilitating tumor transformation.</p>