Virus Genes

, Volume 52, Issue 5, pp 597–605 | Cite as

Proteasomes regulate hepatitis B virus replication by degradation of viral core-related proteins in a two-step manner

  • Zi-Hua Zheng
  • Hui-Ying Yang
  • Lin Gu
  • Xiao-Mou Peng
Article

Abstract

The cellular proteasomes presumably inhibit the replication of hepatitis B virus (HBV) due to degradation of the viral core protein (HBcAg). Common proteasome inhibitors, however, either enhance or inhibit HBV replication. In this study, the exact degradation process of HBcAg and its influences on HBV replication were further studied using bioinformatic analysis, protease digestion assays of recombinant HBcAg, and proteasome inhibitor treatments of HBV-producing cell line HepG2.2.15. Besides HBcAg and hepatitis B e antigen precursor, common hepatitis B core-related antigens (HBcrAgs), the small and the large degradation intermediates of these HBcrAgs (HBcrDIs), were regularly found in cytosol of HepG2.2.15 cells. Further, the results of investigation reveal that the degradation process of cytosolic HBcrAgs in proteasomes consists of two steps: the limited proteolysis into HBcrDIs by the trypsin-like (TL) activity and the complete degradation of HBcrDIs by the chymotrypsin-like (chTL) activity. Concordantly, HBcrAgs and the large HBcrDI or HBcrDIs (including the small HBcrDI) were accumulated when the TL or chTL activity was inhibited, which generally correlated with enhancement and inhibition of HBV replication, respectively. The small HBcrDI inhibited HBV replication by assembling into the nucleocapsids and preventing the victim particles from being mature enough for envelopment. The two-step degradation manner may highlight some new anti-HBV strategies.

Keywords

Hepatitis B virus HBcrAgs Viral replication Protein degradation Proteasomes 

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Zi-Hua Zheng
    • 1
    • 2
    • 3
  • Hui-Ying Yang
    • 1
    • 2
  • Lin Gu
    • 4
  • Xiao-Mou Peng
    • 1
    • 4
  1. 1.Hepatology Laboratory, The Hospital for Liver DiseaseSun Yat-Sen UniversityGuangzhouChina
  2. 2.Department of Infectious Diseases, The Third Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina
  3. 3.Jinan University Clinic, The First Affiliated HospitalJinan UniversityGuangzhouChina
  4. 4.Liver Disease Key Laboratory of Guangdong ProvinceGuangzhouChina

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