Transcriptional Profiles Associated with Marek's Disease Virus in Bursa and Spleen Lymphocytes Reveal Contrasting Immune Responses during Early Cytolytic Infection
Transcriptional Profiles Associated with Marek's Disease Virus in Bursa and Spleen Lymphocytes Reveal Contrasting Immune Responses during Early Cytolytic Infection
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DOI：
10.3390/v12030354
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发表时间：
2020-03-01
期刊：
影响因子：
4.7
通讯作者：
Li, Yongqing
中科院分区：
文献类型：
--
作者：
Jin, Huan;Kong, Zimeng;Li, Yongqing
马立克氏病病毒（MDV）是一种α疱疹病毒，在鸡中引起淋巴增生状态，称为马立克氏病（MD），给家禽业造成严重的经济损失。由于法氏囊和脾脏中的淋巴细胞是MDV感染早期细胞溶解阶段复制的主要靶细胞，因此法氏囊和脾脏中的免疫应答可能是MDV诱导后期免疫的基础。然而，人们对早期淋巴细胞中MDV介导的宿主免疫反应的机制知之甚少。本研究的主要目的是确定参与MDV CVI 988和RB 1B超强毒株感染鸡免疫应答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产生的转录组。我们的研究结果验证了先前表征的基因的表达;然而，它们也揭示了MDV介导的免疫应答期间新基因的表达。结果表明，经CVI 988和vvRB 1B两株病毒攻击后，脾淋巴细胞中分别鉴定出634和313个差异表达基因（DEG）。而在CVI 988和vvRB 1B感染的法氏囊淋巴细胞中分别观察到58和47个DEG。在MDV CVI 988或vvRB 1B攻击后，法氏囊淋巴细胞显示IL-6和IL-4基因表达的变化。令人惊讶的是，脾淋巴细胞在参与免疫应答信号传导的细胞因子和细胞因子受体的表达中表现出压倒性的改变。另一方面，CVI 988和vvRB 1B感染与细胞因子和趋化因子如IL-10、IFN-γ、STAT 1、IRF 1、CCL 19和CCL 26的表达之间没有明显的趋势。然而，与感染vvRB 1B的鸡相比，感染CVI 988的鸡的脾淋巴细胞中IL-1 β、IL-6、IL 8L 1、CCL 4（GGCL 1）和CCL 5的表达谱显著上调。由于这些细胞因子和趋化因子被认为与B细胞活化和抗原信号转导至T细胞有关，因此它们可能表明在感染的早期阶段由疫苗株和强毒株引发的免疫应答的差异。总的来说，我们的研究提供了有价值的数据转录景观使用高通量测序，以了解疫苗介导的保护和致病力MDV在体内的不同机制。
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-gamma, STAT1, IRF1, CCL19, and CCL26. However, the expression profiles of IL-1 beta, 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.