The proteasome activator subunit PSME1 promotes HBV replication by inhibiting the degradation of HBV core protein  

作　　者：Yu Liu Jiaxin Yang Yanyan Wang Qiqi Zeng Yao Fan Ailong Huang Hui Fan 

机构地区：[1]The Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education,Chongqing Medical University,Chongqing 400016,China [2]The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou,Sichuan 646000,China

出　　处：《Genes & Diseases》2024年第6期395-408,共14页基因与疾病（英文）

基　　金：supported by the National Key R&D Program of China (No.2022YFA1303600).

摘　　要：Chronic hepatitis B virus(HBV)infection is a leading cause of liver cirrhosis and he-patocellular carcinoma,representing a global health problem for which a functional cure is difficult to achieve.The HBV core protein(HBc)is essential for multiple steps in the viral life cycle.It is the building block of the nucleocapsid in which viral DNA reverse transcription oc-curs,and its mediation role in viral-host cell interactions is critical to HBV infection persis-tence.However,systematic studies targeting HBc-interacting proteins remain lacking.Here,we combined HBc with the APEX2 to systematically identify HBc-related host proteins in living cells.Using functional screening,we confirmed that proteasome activator subunit 1(PSME1)is a potent HBV-associated host factor.PSME1 expression was up-regulated upon HBV infection,and the protein level of HBc decreased after PSME1 knockdown.Mechanistically,the interac-tion between PSME1 and HBc inhibited the degradation of HBc by the 26S proteasome,thereby improving the stability of the HBc protein.Furthermore,PSME1 silencing inhibits HBV tran-scription in the HBV infection system.Our findings reveal an important mechanism by which PSME1 regulates HBc proteins and may facilitate the development of new antiviral therapies targeting PSME1 function.

关 键 词：26S proteasome APEX2 HBC HBV Host-viral interactions PSME1 

分 类 号：R512.62[医药卫生—内科学]