In vivo cellular and molecular study on duck spleen infected by duck Tembusu virus
In vivo cellular and molecular study on duck spleen infected by duck Tembusu virus
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鸭天布苏病毒感染鸭脾的体内细胞和分子研究
DOI：
10.1016/j.vetmic.2018.12.003
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发表时间：
2019-03-01
影响因子：
3.3
通讯作者：
Chen, Qiusheng
中科院分区：
文献类型：
--
作者：
Sun, Xuejing;Li, Wenqian;Chen, Qiusheng
鸭坦布苏病毒（DTMUV）是一种在脾脏中病毒载量最高的黄病毒新成员。用XZ-2012型DTMUV毒株肌肉注射6月龄产蛋鸭。形态学分析显示，感染后脾脏白髓椭球周围淋巴鞘（PELS）出现空泡变性，特别是在12 ~ 3 dpi。超微结构图像显示细胞及其线粒体和内质网明显肿胀。RNA-seq分析显示，RIG-I信号通路的rlr、下游IRF7和促炎因子IL-6的表达水平在2 hpi和3 dpi时无明显上调，而MHC-II的表达在2 hpi时明显下调。下游抗病毒细胞因子i型IFNs、抗炎细胞因子IL-10、细胞粘附分子（CAMs）、趋化因子及其与淋巴细胞归巢相关的受体的表达水平在3 dpi时显著上调。6 dpi时淋巴细胞数量增加。脾脏免疫功能从9 dpi开始恢复。本研究结果提示，DTMUV通过RIG-I信号通路侵入脾脏，在感染早期通过抑制MHC-II表达增强免疫逃避。此外，DTMUV通过激活IL-6表达诱导PELS病变。此外，DTMUV增加了感染鸭脾脏中rlr、抗病毒i型ifn、淋巴细胞归巢相关基因和蛋白的表达水平以及淋巴细胞数量。综上所述，本研究为鸭脾DTMUV感染的细胞和分子机制提供了新的见解。
Duck Tembusu virus (DTMUV) is a novel member of flavivirus with the highest viral loads in the spleen. Six-month egg-laying shelducks were intramuscularly injected with DTMUV strain XZ-2012. Morphological analysis revealed the presence of vacuolar degeneration in the periellipsoidal lymphatic sheaths (PELS) of spleen white pulp following infection, especially from 12 hpi to 3 dpi. Ultrastructural images showed an obvious swelling of cells and their mitochondria and endoplasmic reticulum. Using RNA-seq analysis, the expression levels of RIG-I like receptors (RLRs), downstream IRF7 and proinflammatory cytokines IL-6 from RIG-I signaling pathway were non-apparently upregulated at 2 hpi and apparently at 3 dpi, while MHC-II expression was obviously down-regulated at 2 hpi. The expression levels of downstream antiviral cytokines type-I IFNs, anti-inflammatory cytokines IL-10, cell adhesion molecules (CAMs), chemokines and their receptors associated with lymphocyte homing were significantly upregulated at 3 dpi. The population of lymphocyte was increased at 6 dpi. The immune function of spleen was recovered starting from 9 dpi. These findings of this study suggest that DTMUV invaded into the spleen via RIG-I signaling pathway and enhanced immune evasion by inhibiting MHC-II expression during the early stage of infection. Additionally, DTMUV induced PELS lesions through activating IL-6 expression. Furthermore, DTMUV increased the expression levels of RLRs, antiviral type-I IFNs, lymphocyte homing-related genes and proteins as well as the number of lymphocytes in the infected duck spleen. Taken altogether, this study provides new insights into the cellular and molecular mechanisms of DTMUV infection in duck spleen.