Fish herpesvirus KLP manipulates Beclin1 to selectively degrade MITA through a precise autophagic manner for immune evasion  

作　　者：Long-Feng Lu Zhuo-Cong Li Xiao-Yu Zhou Can Zhang Cheng-Yan Mou Xue-Li Wang Dan-Dan Chen Li Zhou Jian-Fang Gui Shun Li 

机构地区：[1]Institute of Hydrobiology,Chinese Academy of Sciences,Wuhan,430072,China [2]University of Chinese Academy of Sciences,Beijing,100049,China [3]State Key Laboratory of Freshwater Ecology and Biotechnology,Hubei Hongshan Laboratory,The Innovative Academy of Seed Design,Institute of Hydrobiology,Chinese Academy of Sciences,Wuhan,430072,China [4]College of Fisheries and Life Science,Dalian Ocean University,Dalian,116023,China

出　　处：《Water Biology and Security》2023年第1期59-71,共13页水生生物与安全（英文）

基　　金：supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA24030203 and XDA24030104);National Key Research and Development Program of China(2018YFD0900504);National Natural Science Foundation of China(32073009)and the Youth Innovation Promotion Association provided funding to Shun Li.National Natural Science Foundation of China provided funding to Long-Feng Lu under grant number 32173023.National Natural Science Foundation of China provided funding to Dan-Dan Chen under grant number 32002431.

摘　　要：Control of host autophagy acceleration or attenuation has been confirmed in multiple terrestrial animal viruses.Little is known about such mechanisms in aquatic viruses.Here,we report a selective and ingenious autophagy modulation regulated by kinase-like protein(KLP)of cyprinid herpesvirus 2(CyHV2)to restrict interferon(IFN)production by degrading IFN regulatory factor(IRF)3 activation(MITA).First,exogenous DNA and RNAmediated IFN activation were both abrogated by CyHV2 KLP.The common intersection point of MITA with these two signaling pathways was the interaction with KLP.The C terminus of MITA was indispensable for the interaction and was recruited by KLP in subcellular colocalization analysis.Subsequently,we found that KLP degraded MITA in an autophagy-lysosome-dependent manner and,interestingly,individual KLP could not launch host autophagic flow except in the presence of MITA.KLP was also colocalized with the autophagy components Beclin1 and ATG14 and enhanced Beclin1 stability,but not ATG14,through K63-linked polyubiquitination.Finally,KLP significantly decreased the normal state or MITA-enhanced cellular antiviral capacity.These data demonstrated an elaborate autophagic process manipulated by a fish virus only in the presence of the host target,illuminating a mechanism of aquatic viral immune evasion.

关 键 词：CyHV2 KLP MITA AUTOPHAGY BECLIN1 

分 类 号：S917.4[农业科学—水产科学]