Zhang Yi-Bing, Li Qiong, Gui Jian-Fang
State Key Laboratory of Freshwater Ecology and Biotechnology, Wuhan Center for Developmental Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
Immunogenetics. 2004 Apr;56(1):68-75. doi: 10.1007/s00251-004-0658-1. Epub 2004 Mar 26.
UV-inactivated GCHV (grass carp hemorrhage virus) is able to induce an antiviral state in cultured CAB cells (crucian carp Carassius auratus blastulae embryonic cells) via the production of interferon (IFN). In the current work, the full-length cDNAs of two Mx genes, termed CaMx1 and CaMx2, have been cloned and sequenced from UV-inactivated GCHV-infected and still IFN-producing CAB cells by suppression subtractive hybridization. Their putative proteins show the characteristically structural features of mammalian IFN-induced Mx proteins, including GTP-binding motif, dynamin family signature and leucine zipper motif. CaMx1 exhibits 85% sequence identity to zebrafish MxA and 72-74% to three Atlantic salmon Mx proteins. CaMx2 is most similar to zebrafish MxE, with 80% identity, and then rainbow trout Mx3, with 52%. Constitutive expression was detected by RT-PCR for CaMx1, but not for CaMx2, in normal CAB cells, but their up-regulations could be induced after treatment with active GCHV, UV-inactivated GCHV and CAB IFN. Distinct kinetics of expression was observed for either CaMx1 or CaMx2 corresponding to the three stimuli, and even between CaMx1 and CaMx2, corresponding to the same stimulus. Upon virus infection, the transcriptional induction was strongly blocked for CaMx2 by cycloheximide (CHX), whereas almost nothing was observed for CaMx1. By contrast, following treatment with CAB IFN, CHX did not inhibit either gene transcription. Collectively, these results suggest that there are very distinct mechanisms for modulating the expression of both CaMx1 and CaMx2 in normal and GCHV-infected CAB cells.
紫外线灭活的草鱼出血病毒(GCHV)能够通过产生干扰素(IFN)在培养的鲫鱼囊胚胚胎细胞(CAB细胞)中诱导抗病毒状态。在当前的研究中,通过抑制性消减杂交技术,从紫外线灭活的GCHV感染且仍能产生IFN的CAB细胞中克隆并测序了两个Mx基因的全长cDNA,分别命名为CaMx1和CaMx2。它们的推定蛋白显示出哺乳动物IFN诱导的Mx蛋白的典型结构特征,包括GTP结合基序、发动蛋白家族特征和亮氨酸拉链基序。CaMx1与斑马鱼MxA的序列同一性为85%,与三种大西洋鲑Mx蛋白的序列同一性为72%-74%。CaMx2与斑马鱼MxE最相似,同一性为80%,其次与虹鳟Mx3相似,同一性为52%。通过RT-PCR检测到正常CAB细胞中CaMx1有组成型表达,而CaMx2没有,但在用活性GCHV、紫外线灭活的GCHV和CAB IFN处理后,它们的表达上调。观察到CaMx1或CaMx2对应于三种刺激的表达动力学不同,甚至对应于相同刺激时,CaMx1和CaMx2之间的表达动力学也不同。病毒感染后,环己酰亚胺(CHX)强烈阻断CaMx2的转录诱导,而CaMx1几乎没有变化。相比之下,用CAB IFN处理后,CHX不抑制任何一个基因的转录。总体而言,这些结果表明,在正常和GCHV感染的CAB细胞中,调节CaMx1和CaMx2表达的机制非常不同。