Dynamic and Differential Expression of Duplicated Cxcr4/Cxcl12 Genes Facilitates Antiviral Response in Hexaploid Gibel Carp.
Dynamic and Differential Expression of Duplicated Cxcr4/Cxcl12 Genes Facilitates Antiviral Response in Hexaploid Gibel Carp.
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重复的 Cxcr4/Cxcl12 基因的动态和差异表达促进六倍体银鲤的抗病毒反应
DOI：
10.3389/fimmu.2020.02176
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发表时间：
2020
影响因子：
7.3
通讯作者：
Gui JF
中科院分区：
文献类型：
--
作者：
Lu WJ;Zhou L;Gao FX;Zhou YL;Li Z;Zhang XJ;Wang Y;Gui JF
趋化因子受体 cxcr4 及其配体 cxcl12 在硬骨鱼谱系中进化出了两个旁系同源物。在这项研究中，我们分别从六倍体银鲫（Carassius gibelio）中鉴定出四个重复的 cxcr4 和 cxcl12 基因。鲫鱼疱疹病毒（CaHV）感染后，Cgcxcr4bs和Cgcxcl12as在免疫相关组织中动态差异表达，并且在头肾和脾脏中显着上调。通过注射AMD3100阻断Cxcr4/Cxcl12轴，CaHV感染鱼的出血症状更严重，存活率更低。 AMD3100治疗还抑制了头肾和脾脏中关键抗病毒基因的上调，并导致CaHV在体内更加急性复制。一致的是，在聚（I:C）刺激后，AMD3100 处理的 CAB 细胞中也观察到关键抗病毒基因表达上调的类似抑制。最后，MAPK3和JAK/STAT被确定为CgCxcr4s和CgCxcl12s参与促进体外抗病毒反应的可能途径。
Chemokine receptor cxcr4 and its ligand cxcl12 have evolved two paralogs in the teleost lineage. In this study, we have identified four duplicated cxcr4 and cxcl12 genes from hexaploid gibel carp, Carassius gibelio, respectively. Cgcxcr4bs and Cgcxcl12as were dynamically and differentially expressed in immune-related tissues, and significantly up-regulated in head kidney and spleen after crucian carp herpesvirus (CaHV) infection. Blocking Cxcr4/Cxcl12 axis by injecting AMD3100 brought more severe bleeding symptom and lower survival rate in CaHV-infected fish. AMD3100 treatment also suppressed the up-regulation of key antiviral genes in head kidney and spleen, and resulted in more acute replication of CaHV in vivo. Consistently, the similar suppression of up-regulated expression of key antiviral genes were also observed in CAB cells treated by AMD3100 after poly(I:C) stimulation. Finally, MAPK3 and JAK/STAT were identified as the possible pathways that CgCxcr4s and CgCxcl12s participate in to promote the antiviral response in vitro.
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