SPOP inhibits HBV transcription and replication by ubiquitination and degradation of HNF1α
作者全名："Pi, Yubo; Li, Yang; Yan, Qi; Luo, Huimin; Zhou, Peng; Chang, Wenyi; Gong, Deao; Hu, Yuan; Wang, Kai; Tang, Ni; Huang, Ailong; Chen, Yanmeng"
作者地址："[Pi, Yubo; Yan, Qi; Luo, Huimin; Zhou, Peng; Chang, Wenyi; Gong, Deao; Hu, Yuan; Wang, Kai; Tang, Ni; Huang, Ailong] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis,Minist, Chongqing, Peoples R China; [Li, Yang] Peking Univ, Chongqing Big Data Res Inst, Chongqing, Peoples R China; [Chen, Yanmeng] Chongqing Med Univ, Dept Lab Med, Minist Educ, Key Lab Lab Med Diagnost, Chongqing, Peoples R China; [Chen, Yanmeng] Chongqing Med Univ, Minist Educ, Key Lab Lab Med Diagnost, DepT Lab Med, Chongqing 400016, Peoples R China; [Huang, Ailong] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infectious Dis,Key Lab Mol Biol Infect Dis,Mi, Chongqing 400016, Peoples R China"
通信作者："Chen, YM (通讯作者)，Chongqing Med Univ, Minist Educ, Key Lab Lab Med Diagnost, DepT Lab Med, Chongqing 400016, Peoples R China.; Huang, AL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infectious Dis,Key Lab Mol Biol Infect Dis,Mi, Chongqing 400016, Peoples R China."
来源：JOURNAL OF MEDICAL VIROLOGY
ESI学科分类：MICROBIOLOGY
WOS号：WOS:001138650800038
JCR分区：Q1
影响因子：6.8
年份：2023
卷号：95
期号：12
开始页：
结束页：
文献类型：Article
关键词：hepatitis B virus; HNF1 alpha; host factor; SPOP; ubiquitination
摘要："Hepatitis B virus (HBV) infection remains a significant public health burden worldwide. The persistence of covalently closed circular DNA (cccDNA) within the nucleus of infected hepatocytes is responsible for the failure of antiviral treatments. The ubiquitin proteasome system (UPS) has emerged as a promising antiviral target, as it can regulate HBV replication by promoting critical protein degradation in steps of viral life cycle. Speckle-type POZ protein (SPOP) is a critical adaptor for Cul3-RBX1 E3 ubiquitin ligase complex, but the effect of SPOP on HBV replication is less known. Here, we identified SPOP as a novel host antiviral factor against HBV infection. SPOP overexpression significantly inhibited the transcriptional activity of HBV cccDNA without affecting cccDNA level in HBV-infected HepG2-NTCP and primary human hepatocyte cells. Mechanism studies showed that SPOP interacted with hepatocyte nuclear factor 1 alpha (HNF1 alpha), and induced HNF1 alpha degradation through host UPS pathway. Moreover, the antiviral role of SPOP was also confirmed in vivo. Together, our findings reveal that SPOP is a novel host factor which inhibits HBV transcription and replication by ubiquitination and degradation of HNF1 alpha, providing a potential therapeutic strategy for the treatment of HBV infection."
基金机构："111 Project; The 111 Project [D20028]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202100464]; Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau) [2023DBXM007]; CQMU Program for Youth Innovation in Future Medicine [W0160, W0036, W0101]; Kuanren talents program of the second affiliated hospital of Chongqing Medical University; Innovative and Entrepreneurial Team of Chongqing Talents Plan; National Natural Science Foundation of China [82102377, U20A20392]; Natural Science Foundation Project of Chongqing [cstc2021jcyj-msxmX0276]; First batch of key Disciplines On Public Health in Chongqing"
基金资助正文："111 Project, Grant/Award Number: D20028; Science and Technology Research Program of Chongqing Municipal Education Commission, Grant/Award Number: KJQN202100464; Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau), Grant/Award Number: 2023DBXM007; CQMU Program for Youth Innovation in Future Medicine, Grant/Award Numbers: W0160, W0036, W0101; Kuanren talents program of the second affiliated hospital of Chongqing Medical University; Innovative and Entrepreneurial Team of Chongqing Talents Plan; National Natural Science Foundation of China, Grant/Award Numbers: 82102377, U20A20392; Natural Science Foundation Project of Chongqing, Grant/Award Number: cstc2021jcyj-msxmX0276; First batch of key Disciplines On Public Health in Chongqing"
