Hepatitis B virus core protein dimer‑dimer interface is critical for viral replication
| Autor: | Chang‑Long Zheng, Yong‑Mei Fu, Kai Deng, Zhan‑Xue Xu, Yong Zou |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Hepatitis B virus replication Cancer Research Protein Conformation viruses 030106 microbiology Protein dimer Virus Replication medicine.disease_cause Biochemistry 03 medical and health sciences chemistry.chemical_compound Capsid Protein structure core protein Genetics medicine Humans Molecular Biology Gel electrophoresis Mutation virion Virus Assembly DNA replication virus diseases Hep G2 Cells Articles Hepatitis B Hepatitis B Core Antigens Molecular biology digestive system diseases 030104 developmental biology Oncology chemistry Viral replication Molecular Medicine Protein Multimerization dimer-dimer interface |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2018.9620 |
| Popis: | Hepatitis B virus (HBV) core protein (HBc) serves pivotal roles in the viral life cycle, particularly serving as the basic unit for capsid assembly, and is closely associated with HBV genome replication and progeny virion production. Previous studies have demonstrated that HBc has at least two functional interfaces; two HBc monomers form a homodimer via an intradimer interface, and then 90 or 120 homodimers form an icosahedral capsid via a dimer-dimer interface. In the present study, the role of the HBc dimer-dimer interface in HBV replication was investigated. A panel of residues located at the dimer-dimer interface were identified based on the crystal structure of HBc. Native gel electrophoresis and western blotting revealed that, despite mutations in the dimer-dimer interface, HBc formed a capsid-like structure, whereas mutations at amino acid residues 23–39 completely disrupted capsid assembly. Using denaturing gel electrophoresis, Southern and Northern blotting, and quantitative polymerase chain reaction, it was demonstrated that none of the mutations in the dimer-dimer interface supported pregenomic RNA encapsidation or DNA replication. In addition, these mutants interacted with the wild-type (WT) HBc monomer and inhibited WT genome replication and virion production in a dose-dependent manner. However, the quantity of covalently closed circular DNA in the nucleus was not affected. The present study highlighted the importance of the HBc dimer-dimer interface for normal capsid function and demonstrated that the HBc dimer-dimer interface may be a novel antiviral target. |
| Databáze: | OpenAIRE |
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