虹彩病毒ISKNV利用HIF-1信号通路调控宿主糖代谢

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus. Megalocytivirus has been implicated in infections of more than 50 fish species and currently threatens the aquaculture industry, causing great economic losses in China. Glucose metabolism is the source of intracellular energy and biosynthetic material. Viruses manipulate host glucose metabolism by many ways, which plays an important role in virus replication, transmission and pathogenicity. HIF-1(Hypoxia-inducible factors-1) signaling pathway is a significant glucose metabolic regulation pathways in cells and is targeted by many viruses, which manipulate host glucose metabolism. Previous study has predicted that HIF-1 signaling pathway is regulated by ISKNV. Research focused on ISKNV is as following: Clarify the regulation on host HIF-1 signaling pathway by ISKNV and the molecule mechanism. Confirm the effect of ISKNV regulating HIF-1 on host cell glucose metabolism. Analyse the relationship of ISKNV regulating HIF-1 on host glucose metabolism and pathogenicity. The research will reveal how Megalocytivirus manipulate host glucose metabolism. From the perspective of metabolic regulation, reveal the Megalocytivirus pathogenic mechanism. Thus providing theoretical basis for controlling iridescent virus.

传染性脾肾坏死病毒（ISKNV）是虹彩病毒科肿大细胞病毒属的代表种，感染50多种经济鱼类，对我国鱼类养殖业造成重大经济损失。糖类代谢是细胞内能量和生物合成原材料的来源，病毒能通过多种方式调控宿主糖代谢，对于病毒的复制、传播及其致病性都有重要意义。HIF-1信号通路（细胞低氧应激信号通路）是细胞内重要的糖代谢调控途径，也是许多病毒调控细胞糖代谢的重要靶标。申请人前期的研究预示ISKNV对HIF-1信号通路具有调控作用。因此，本课题针对ISKNV，拟重点开展以下三个方面的研究：①阐明ISKNV对宿主HIF-1信号通路的调控及分子机制；②明确ISKNV调控宿主HIF-1信号通路对宿主糖代谢的影响；③分析ISKNV对宿主糖代谢的调控与病毒致病性的关系。本研究以期阐明肿大细胞病毒对宿主细胞糖代谢的调控作用及其机制；从代谢调控的角度，揭示肿大细胞病毒的致病机制。从而为控制虹彩病毒提供理论基础。

传染性脾肾坏死病毒（ISKNV）是虹彩病毒科肿大细胞病毒属的代表种，感染50多种经济鱼类，对我国鱼类养殖业造成重大的经济损失。HIF-1信号通路（低氧应激信号通路）是细胞内重要的代谢调控途径。因此，该信号通路也是许多病毒调控细胞代谢的重要靶标。通过本课题的研究，阐明了ISKNV对鳜HIF-1信号通路的调控及分子机制；明确ISKNV调控宿主HIF-1信号通路对宿主细胞糖代谢的影响。HIF-1信号通路（低氧应激信号通路）同时也是动物感受低氧应激的关键信号传导途，本课题进一步探讨了低氧环境胁迫与传染性脾肾坏死病毒病之间的关系。阐明了“低氧胁迫→激活鳜鱼HIF-信号通路→促进ISKNV复制”的证据链，从而揭示传染性脾肾坏死病毒病的低氧胁迫致病机理，发展和丰富鱼类虹彩病毒防控的理论和技术。