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Hepatitis B virus core protein dimer‑dimer interface is critical for viral replication

  • Authors:
    • Chang‑Long Zheng
    • Yong‑Mei Fu
    • Zhan‑Xue Xu
    • Yong Zou
    • Kai Deng
  • View Affiliations / Copyright

    Affiliations: Department of Emergency, The Third Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510630, P.R. China, Institute of Human Virology and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Blood Transfusion, The Third Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510630, P.R. China, Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510060, P.R. China
    Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 262-270
    |
    Published online on: November 2, 2018
       https://doi.org/10.3892/mmr.2018.9620
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Zheng CL, Fu YM, Xu ZX, Zou Y and Deng K: Hepatitis B virus core protein dimer‑dimer interface is critical for viral replication. Mol Med Rep 19: 262-270, 2019.
APA
Zheng, C., Fu, Y., Xu, Z., Zou, Y., & Deng, K. (2019). Hepatitis B virus core protein dimer‑dimer interface is critical for viral replication. Molecular Medicine Reports, 19, 262-270. https://doi.org/10.3892/mmr.2018.9620
MLA
Zheng, C., Fu, Y., Xu, Z., Zou, Y., Deng, K."Hepatitis B virus core protein dimer‑dimer interface is critical for viral replication". Molecular Medicine Reports 19.1 (2019): 262-270.
Chicago
Zheng, C., Fu, Y., Xu, Z., Zou, Y., Deng, K."Hepatitis B virus core protein dimer‑dimer interface is critical for viral replication". Molecular Medicine Reports 19, no. 1 (2019): 262-270. https://doi.org/10.3892/mmr.2018.9620
Copy and paste a formatted citation
x
Spandidos Publications style
Zheng CL, Fu YM, Xu ZX, Zou Y and Deng K: Hepatitis B virus core protein dimer‑dimer interface is critical for viral replication. Mol Med Rep 19: 262-270, 2019.
APA
Zheng, C., Fu, Y., Xu, Z., Zou, Y., & Deng, K. (2019). Hepatitis B virus core protein dimer‑dimer interface is critical for viral replication. Molecular Medicine Reports, 19, 262-270. https://doi.org/10.3892/mmr.2018.9620
MLA
Zheng, C., Fu, Y., Xu, Z., Zou, Y., Deng, K."Hepatitis B virus core protein dimer‑dimer interface is critical for viral replication". Molecular Medicine Reports 19.1 (2019): 262-270.
Chicago
Zheng, C., Fu, Y., Xu, Z., Zou, Y., Deng, K."Hepatitis B virus core protein dimer‑dimer interface is critical for viral replication". Molecular Medicine Reports 19, no. 1 (2019): 262-270. https://doi.org/10.3892/mmr.2018.9620
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