与马立克氏病病毒相关的转录谱在法氏囊和脾脏淋巴细胞中揭示了早期细胞溶解感染期间相反的免疫反应。
Transcriptional Profiles Associated with Marek's Disease Virus in Bursa and Spleen Lymphocytes Reveal Contrasting Immune Responses during Early Cytolytic Infection.
机构信息
Research Center for Infectious Disease in Livestock and Poultry, Beijing Academy of Agricultural and Forestry Sciences, Beijing 100097, China.
Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agricultural and Forestry Sciences, Beijing 100097, China.
出版信息
Viruses. 2020 Mar 23;12(3):354. doi: 10.3390/v12030354.
Marek's disease virus (MDV), an alpha herpes virus, causes a lymphoproliferative state in chickens known as Marek's disease (MD), resulting in severe monetary losses to the poultry industry. Because lymphocytes of bursa of Fabricius and spleen are prime targets of MDV replication during the early cytolytic phase of infection, the immune response in bursa and spleen should be the foundation of late immunity induced by MDV. However, the mechanism of the MDV-mediated host immune response in lymphocytes in the early stage is poorly understood. The present study is primarily aimed at identifying the crucial genes and significant pathways involved in the immune response of chickens infected with MDV CVI988 and the very virulent RB1B (vvRB1B) strains. Using the RNA sequencing approach, we analyzed the generated transcriptomes from lymphocytes isolated from chicken bursa and spleen. Our findings validated the expression of previously characterized genes; however, they also revealed the expression of novel genes during the MDV-mediated immune response. The results showed that after challenge with CVI988 or vvRB1B strains, 634 and 313 differentially expressed genes (DEGs) were identified in splenic lymphocytes, respectively. However, 58 and 47 DEGs were observed in bursal lymphocytes infected with CVI988 and vvRB1B strains, respectively. Following MDV CVI988 or vvRB1B challenge, the bursal lymphocytes displayed changes in IL-6 and IL-4 gene expression. Surprisingly, splenic lymphocytes exhibited an overwhelming alteration in the expression of cytokines and cytokine receptors involved in immune response signaling. On the other hand, there was no distinct trend between infection with CVI988 and vvRB1B and the expression of cytokines and chemokines, such as IL-10, IFN-γ, STAT1, IRF1, CCL19, and CCL26. However, the expression profiles of IL-1β, IL-6, IL8L1, CCL4 (GGCL1), and CCL5 were significantly upregulated in splenic lymphocytes from chickens infected with CVI988 compared with those of chickens infected with vvRB1B. Because these cytokines and chemokines are considered to be associated with B cell activation and antigenic signal transduction to T cells, they may indicate differences of immune responses initiated by vaccinal and virulent strains during the early phase of infection. Collectively, our study provides valuable data on the transcriptional landscape using high-throughput sequencing to understand the different mechanism between vaccine-mediated protection and pathogenesis of virulent MDV in vivo.
马立克氏病病毒（MDV）是一种α疱疹病毒，可引起鸡的淋巴组织增生性疾病，称为马立克氏病（MD），给家禽业造成严重的经济损失。由于法氏囊和脾脏的淋巴细胞是 MDV 复制的主要靶细胞，因此在感染的早期细胞溶解阶段，法氏囊和脾脏的免疫反应应该是 MDV 诱导的晚期免疫的基础。然而，MDV 介导的宿主免疫反应在淋巴细胞中的机制尚不清楚。本研究主要目的是鉴定感染 MDV CVI988 和非常毒力 RB1B（vvRB1B）株的鸡淋巴细胞中的关键基因和重要途径。使用 RNA 测序方法，我们分析了从鸡法氏囊和脾脏分离的淋巴细胞生成的转录组。我们的研究结果验证了先前表征基因的表达；然而，它们还揭示了 MDV 介导的免疫反应中新型基因的表达。结果表明，用 CVI988 或 vvRB1B 株攻毒后，分别在脾脏淋巴细胞中鉴定出 634 个和 313 个差异表达基因（DEGs）。然而，用 CVI988 和 vvRB1B 株感染的法氏囊淋巴细胞中分别观察到 58 个和 47 个 DEGs。用 MDV CVI988 或 vvRB1B 攻毒后，法氏囊淋巴细胞中 IL-6 和 IL-4 基因的表达发生变化。令人惊讶的是，脾脏淋巴细胞中涉及免疫反应信号的细胞因子和细胞因子受体的表达发生了压倒性的改变。另一方面，用 CVI988 和 vvRB1B 感染之间的细胞因子和趋化因子（如 IL-10、IFN-γ、STAT1、IRF1、CCL19 和 CCL26）的表达没有明显的趋势。然而，与感染 vvRB1B 相比，感染 CVI988 的鸡的脾脏淋巴细胞中 IL-1β、IL-6、IL8L1、CCL4（GGCL1）和 CCL5 的表达显著上调。因为这些细胞因子和趋化因子被认为与 B 细胞激活和抗原信号转导到 T 细胞有关，它们可能表明疫苗和毒力株在感染早期启动的免疫反应之间的差异。总的来说，我们的研究使用高通量测序提供了有价值的转录谱数据，以了解体内疫苗介导的保护和马立克氏病强毒致病的不同机制。
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