虹彩病毒ISKNV免疫逃避与致病的分子机制

Aquaculture in China accounts for nearly 70% of world aquaculture production, but the disease has become the main obstacle to sustainable aquaculture development. Iridoviruses are large icosahedral cytoplasmic DNA viruses that contain circularly permutated, terminally redundant, double-stranded DNA genomes.The current members of the family Iridoviridae are divided into five genera: Iridovirus, Chloriridovirus, Ranavirus, Lymphocystivirus, and Megalocytivirus. 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.For this reason, reasearch is being conducted to understand the mechanism of ISKNV escaping the fish innate immune system. Here, we plan to reaserch on the Pathogenicity association with ISKNV regulated fish interferon signal pathways, toll-like signal pathway, cell apoptosis and ISKNV escape from immune cells, as well as the molecular mechanism of ISKNV causing massive bleeding, to clarm the cellular mechamism of iridovirs evasion of fish innate immune. Our work may help further improve our unserstanding of the iroidovirus evasion, and control the iridovirus disease of fish.

我国是世界水产养殖产业大国，随着养殖品种的增多和养殖规模的扩大，病害已经成为水产养殖可持续发展的主要障碍。虹彩病毒是水产养殖鱼类重要的病毒性病原。传染性脾肾坏死病毒是虹彩病毒科肿大细胞病毒属的代表种，感染50多种名贵经济鱼类，对我国鱼类养殖业造成重大的经济损失。本课题拟通过对ISKNV调控鱼类干扰素途径与致病性、ISKNV调控鱼类TOLL信号转导途径与致病性、ISKNV调控鱼类凋亡与致病性、ISKNV逃避细胞免疫与致病性和ISKNV致鱼类出血的分子机制等研究，系统阐明虹彩病毒ISKNV调控和逃避鱼类先天性免疫的分子机制，从免疫逃避的角度揭示ISKNV的致病机理，为最终有效防控鱼类虹彩病毒病奠定理论基础。

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，能感染50多种名贵经济鱼类，给我国鱼类养殖业造成重大的经济损失。本项目开展了ISKNV调控鱼类干扰素途径、ISKNV调控鱼类ILK信号转导途径、ISKNV调控鱼类凋亡、ISKNV逃避细胞免疫和ISKNV逃逸宿主HIF-1信号通路等研究，系统阐明虹彩病毒ISKNV调控和逃避鱼类先天性免疫的分子机制。研究结果显示ISKNV利用vSOCS与JAK蛋白互作逃逸干扰素的抗病毒途径，并且利用外泌体途径逃逸干扰素的抗病毒过程；通过编码ORF119L与宿主PINCH蛋白互作逃逸宿主的ILK信号通路；通过编码ORF005L定位于线粒体引起细胞凋亡，编码FLP调控NFκB活性参与病毒对细胞凋亡的调控；通过编码VP08R和VP23R蛋白与宿主nidogen-1互作形成伪基底膜逃逸宿主的细胞免疫；通过编码ORF077R与宿主FIH蛋白互作逃逸宿主HIF-1信号途径，调控宿主免疫代谢过程。上述研究结果从免疫逃避的角度，揭示出ISKNV的致病机理，为鱼类虹彩病毒病的防控提供了重要的理论基础。项目执行期间，发表SCI收录论文11篇，第一标注论文有9篇，其中JCR一区文章3篇，二区2篇，包括2篇发表在Journal of Virology杂志，3篇发表在Scientific Reports杂志；申请国家发明专利6项；并培养10名硕士研究生和8名博士研究生。