Department of Animal Genetics and Breeding, National Engineering Laboratory for Animal Breeding, MOA Laboratory of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
Poult Sci. 2012 Sep;91(9):2130-8. doi: 10.3382/ps.2012-02226.
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, IL6, IL18, IFNA, and IFNG were nondifferentially expressed, which indicates host inflammatory response was impaired. The IL10 and TNFRSF8 genes were upregulated in tumorous spleens. We speculated that IL10 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 TNFRSF8 promoter could be enhanced by MDV oncogene Meq. In this study, the increased expression of TNFRSF8 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 IGFBP7 was considered to be associated with MD lymphoma transformation. Gene expression change of multiple regulatory pathways indicated their involvements in facilitating tumor transformation.
马立克氏病是一种由马立克氏病病毒（MDV）引起的鸡的病毒性肿瘤性疾病。已经在不同的 MDV 感染阶段研究了基因表达模式，但对晚期肿瘤转化阶段的研究有限。在这项实验中，使用了 44K Agilent 鸡全基因组表达微阵列来分析 MDV 感染后严重患病鸡的肿瘤脾脏（TS）与幸存者（SS）的明显正常脾脏以及对照的非感染脾脏（NS）之间的差异表达。TS 与 NS 相比，有 4317 个差异表达（DE）基因。然而，SS 与 NS 之间没有检测到 DE 基因，这表明幸存者脾脏中的基因活性维持或恢复到了稳态。肿瘤脾脏中下调的基因主要富集在细胞因子-细胞因子受体相互作用途径中，并且在马立克氏病研究中经常研究的基因，如 IL6、IL18、IFNA 和 IFNG，没有差异表达，这表明宿主炎症反应受损。IL10 和 TNFRSF8 基因在肿瘤脾脏中上调。我们推测，IL10 可能被 MDV 利用来逃避宿主的免疫监视，就像 Epstein-Barr 病毒那样，它刺激 T 细胞分泌 IL10 来颠覆免疫反应。先前的研究报告称，TNFRSF8 启动子的转录可以被 MDV 癌基因 Meq 增强。在这项研究中，TNFRSF8 的表达增加表明 MDV 与 TNFRSF8 之间的相互作用，这可能有助于发病机制和肿瘤转化。与未感染的脾脏相比，IGF 系统的许多成员在肿瘤脾脏中的表达发生了变化。IGFBP7 的下调被认为与 MD 淋巴瘤转化有关。多个调节途径的基因表达变化表明它们参与了促进肿瘤转化。
