鱼类蛋白激酶Z(PKZ)和蛋白激酶R(PKR)在响应病毒入侵时所承担的功能

Fish, cold blooded vertebrates, have some very unique immune factors and immune system. For example, there are PKR and its duplication PKZ co-exist in fish genomes. PKR (double-stranded RNA-dependent protein kinase) is a dsRNA receptor in cell, and PKZ (Protein Kinase Containing Z-DNA Binding Domain) is a newly discovered Z-DNA/Z-RNA recognition receptors. Both of them can response to viral infection. Previous studies have shown that fish PKZ and PKR have some functional overlaps or divergences in virus-infected cells. To date, the studies on PKZ or PKR functions were mainly focused on eIF2α phosphorylation. It could only display a simple relationship between the two proteins for us, rather than a systematic and panoramic view of PKZ, PKR with many intracellular molecules in the complex signal-transduction networks. So we can not fully understand the functions of fish PKZ, PKR in response to viral invasion. Accordingly, we plan to carry out the following studies. (1)To analysis transcriptional regulation mechanisms of PKZ, PKR. (2)To capture, screen and identify the substrates of PKZ, PKR. (3)To study the interaction of PKZ, PKR with their substrates and to understand the cooperative or distinct roles of PKZ, PKR. The ultimate aim of the research is to explore a new immunity method in teleosts. This project will help us to further understand the molecular mechanisms of interferon antiviral response in fish.

鱼类属于变温脊椎动物，拥有一些非常独特的免疫因子和免疫机制。鱼类具有PKR及其复制物PKZ，它们串联存在于基因组中。在细胞中，PKR是一种dsRNA受体，PKZ为一个Z-DNA/Z-RNA识别受体，它们都能对病毒侵染产生应答。前期研究表明，在病毒侵入鱼类细胞时，PKZ和PKR有功能的重叠，但也有作用机制的分化。目前对于鱼类PKZ、PKR研究只在eIF2α上有交集，很难系统、全景式地反映PKZ、PKR在细胞内与众多互作分子所构成的纷繁复杂的信号转导网络，也就无法全面了解鱼类PKZ、PKR在细胞应激时所担负的功能。因此，本研究拟在病毒感染的草鱼细胞中开展：一、鱼类PKZ、PKR转录调控的分子机制。二、PKZ、PKR作用底物的捕获、筛选和鉴定。三、研究PKZ、PKR与底物分子的互作，了解它们功能的趋同性和分化性。本项目的实施，有利于我们探索鱼类新的免疫方式和进一步了解干扰素抗病毒的分子机制。

鱼类属于变温脊椎动物，拥有一些非常独特的免疫因子和免疫机制。鱼类具有PKR 及其复制物PKZ，它们串联存在于基因组中。在细胞中，PKR 是一种dsRNA 受体，PKZ 为一个Z-DNA/Z-RNA 识别受体，它们都能对病毒侵染产生应答。前期研究表明，在病毒侵入鱼类细胞时，PKZ 和PKR 有功能的重叠，但也有作用机制的分化。目前对于鱼类PKZ、PKR 研究只在eIF2α上有交集，很难系统、全景式地反映PKZ、PKR 在细胞内与众多互作分子所构成的纷繁复杂的信号转导网络，也就无法全面了解鱼类PKZ、PKR 在细胞应激时所担负的功能。因此，本研究拟在病毒感染的草鱼细胞中开展：一、鱼类PKZ、PKR 转录调控的分子机制。二、PKZ、PKR 作用底物的捕获、筛选和鉴定。三、研究PKZ、PKR 与底物分子的互作，了解它们功能的趋同性和分化性。本项目的实施，有利于我们探索鱼类新的免疫方式和进一步了解干扰素抗病毒的分子机制。