title: HBx affects CUL4-DDB1 function in both positive and negative manners.
abstract: Hepatitis B virus (HBV) infection is a major public health problem by affecting 350 million people worldwide. The mechanisms that regulate HBV gene expression and viral replication remain poorly understood. HBx is known as the central regulator for HBV replication and is associated with the CUL4-DDB1 ubiquitin ligase through H-box motif. Here, we show that blocking the activity of DDB1 by RNA interfering inhibited viral production and gene expression of HBV, and direct association of HBx with DDB1 promoted viral activities, indicating that DDB1 function is required for viral production. On the other hand, HBx interfered with DDB1-dependent polyubiquitination of PRMT1, arginine methyltransferase 1, suggesting that HBx can also block the function of a subset of CUL4-DDB1 E3 ligases. Thus, we conclude that HBx regulates the function of DDB1 in both positive and negative manners in the context of distinct CUL4-DDB1 complexes and plays different roles in HBV replication cycle.
authors.affiliation: Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, PR China.
authors.forename: Liandi
authors.initials: L
authors.lastname: Guo
authors.affiliation: Developmental and Stem Cell Institute, Department of Pediatrics, West China Second University Hospital, Chengdu 610041, PR China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology & Immunology, Fenyang College of Shanxi Medical University, Fenyang 032200, PR China.
authors.forename: Laifeng
authors.initials: L
authors.lastname: Ren
authors.affiliation: Developmental and Stem Cell Institute, Department of Pediatrics, West China Second University Hospital, Chengdu 610041, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Developmental and Stem Cell Institute, Department of Pediatrics, West China Second University Hospital, Chengdu 610041, PR China.
authors.forename: Si
authors.initials: S
authors.lastname: Wang
authors.affiliation: Developmental and Stem Cell Institute, Department of Pediatrics, West China Second University Hospital, Chengdu 610041, PR China.
authors.forename: Yuding
authors.initials: Y
authors.lastname: Weng
authors.affiliation: Developmental and Stem Cell Institute, Department of Pediatrics, West China Second University Hospital, Chengdu 610041, PR China.
authors.forename: Zizhi
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Developmental and Stem Cell Institute, Department of Pediatrics, West China Second University Hospital, Chengdu 610041, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Disease, Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.
authors.forename: Huaidong
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, PR China. Electronic address: lmingyuan16@yahoo.com.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, PR China. Electronic address: cjzhang49@hotmail.com.
authors.forename: Chongjie
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Developmental and Stem Cell Institute, Department of Pediatrics, West China Second University Hospital, Chengdu 610041, PR China. Electronic address: congliu@scu.edu.cn.
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D044842:Cullin Proteins / Q000502:physiology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D006515:Hepatitis B virus / Q000502:physiology; D006801:Humans; D011484:Protein-Arginine N-Methyltransferases / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000502:physiology*; D054875:Ubiquitination; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication
chemical_list: D044842:Cullin Proteins; C091435:DDB1 protein, human; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: DDB1; HBx; Hepatitis B virus; PRMT1; cccDNA