Role of Ras-related Nuclear Protein/Polypyrimidine Tract Binding Protein in Facilitating the Replication of Hepatitis C Virus  

作　　者：Jihua Xue Jun Cheng Xuejiao Ma Yixian Shi Huafa Yin Yufeng Gao Jiabin Li 

机构地区：[1]Department of Infectious Diseases,The First Affiliated Hospital of Anhui Medical University,Hefei,Anhui,China [2]Department of Hepatology,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou,Fujian,China

出　　处：《Journal of Clinical and Translational Hepatology》2021年第4期458-465,共8页临床与转化肝病杂志（英文版）

基　　金：The work was supported by the Anhui Provincial Natural Science Foundation(1608085QH172);States S&T Projects of 13th Five Year(2018ZX10302206),Chinese Founda-tion for Hepatitis Prevention and Control(TQGB20200151,TQGB20180367);Anhui Key Program of Medical Scien-tific Research of China(#2010A010).

摘　　要：Background and Aims:Ras-related nuclear(RAN)protein is a small GTP-binding protein that is indispensable for the translocation of RNA and proteins through the nuclear pore complex.Recent studies have indicated that RAN plays an important role in virus infection.However,the role of RAN in hepatitis C virus(HCV)infection is unclear.The objective of this study was to investigate the role and underlying mechanisms of RAN in HCV infection.Methods:Huh7.5.1 cells were infected with the JC1-Luc virus for 24 h and then were incubated with complete medium for an additional 48 h.HCV infection and RAN expression were determined using luciferase assay,quantitative reverse transcription-PCR and western blotting.Small interfering RNA was used to silence RAN.Western blotting and immunofluorescence were used to evaluate the cytoplasmic translocation of polypyrimidine tract-binding(PTB),and coimmunoprecipitation was used to examine the interaction between RAN and PTB.Results:HCV infection significantly induced RAN expression and cytoplasmic redistribution of PTB.Knockdown of RAN dramatically inhibited HCV infection and the cytoplasmic accumulation of PTB.Colocalization of RAN and PTB was determined by immunofluorescence,and a direct interaction of RAN with PTB was demonstrated by coimmunoprecipitation.Conclusions:PTB in the host cytoplasm is directly associated with HCV replication.These findings demonstrate that the involvement of RAN in HCV infection is mediated by influencing the cytoplasmic translocation of PTB.

关 键 词：Ras-related nuclear protein HCV infection Polypyrimidine tractbinding protein Nucleo-cytoplasmic translocation Novel anti-HCV therapeutics 

分 类 号：R51[医药卫生—内科学]