Site-specific mutation of the hepatitis B virus enhancer II B1 element: effect on virus transcription and replication.
The hepatitis B virus (HBV) enhancer II (EII) is highly liver-specific and plays an important role in regulating the transcription of all HBV genes. In this report, mutational analysis on the B1F-binding site in the major functional unit of HBV EII is described. The activity of HBV EII in EII-CAT reporter plasmids was significantly decreased when the sequence of the B1F-binding site in EII was mutated. Furthermore, a single point mutation in the B1 element that aborted the binding of B1F caused a dramatic decrease in viral gene transcription initiated from the HBV core promoter, which resulted in a reduction of the production of the HBV e antigen and pregenomic RNA, the template for viral DNA replication. In conclusion, the interaction of B1F with its target binding sequence in the EII region is crucial for liver-specific transcription and DNA replication of the virus.
Xie
Youhua
Y
Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Shanghai, China2.|Max-Planck-Institut für Biochemie1 and 3Am Klopferspitz 18a and D-82152 Martinsried, Germany.
Li
Mei
M
Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Shanghai, China2.
Wang
Yuan
Y
Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Shanghai, China2.
Hofschneider
Peter Hans
PH
Max-Planck-Institut für Biochemie1 and 3Am Klopferspitz 18a and D-82152 Martinsried, Germany.
Weiss
Ludwig
L
Max-Planck-Institut für Biochemie1 and 3Am Klopferspitz 18a and D-82152 Martinsried, Germany.
D004261:DNA Replication; D004268:DNA-Binding Proteins; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D006513:Hepatitis B e Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016297:Mutagenesis, Site-Directed; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D004268:DNA-Binding Proteins; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; C082631:NR5A2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors