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Review
. 2019 May 30;16(1):73.
doi: 10.1186/s12985-019-1183-z.

The interaction of hepatitis B virus with the ubiquitin proteasome system in viral replication and associated pathogenesis

Fanyun Kong  1 , Hongjuan You  1 , Delong Kong  1 , Kuiyang Zheng  1   2 , Renxian Tang  3   4
Affiliations
Review

The interaction of hepatitis B virus with the ubiquitin proteasome system in viral replication and associated pathogenesis

Fanyun Kong et al. Virol J. .

Abstract

Background: The ubiquitin proteasome system (UPS) regulates the expression levels of cellular proteins by ubiquitination of protein substrates followed by their degradation via the proteasome. As a highly conserved cellular degradation mechanism, the UPS affects a variety of biological processes and participates in viral propagation.

Main body: During hepatitis B virus (HBV) infection, the UPS is shown to act as a double-edged sword in viral pathogenesis. On the one hand, the UPS acts as a host defense mechanism to selectively recognize HBV proteins as well as special cellular proteins that favor the viral life cycle and induces their ubiquitin-dependent proteasomal degradation to limit HBV infection. On the other hand, the HBV has evolved to subvert the UPS function for its own advantage. Moreover, in the infected hepatocytes, certain cellular proteins that are dependent on the UPS are involved in abnormal biological processes which are mediated by HBV.

Conclusion: The molecular interaction of HBV with the UPS to modulate viral propagation and pathogenesis is summarized in the review. Considering the important role of the UPS in HBV infection, a better understanding of the HBV-UPS interaction could provide novel insight into the mechanisms that are involved in viral replication and pathogenesis and help to develop potential treatment strategies targeting the UPS.

Keywords: Hepatitis B virus; Pathogenesis; Proteasome; Replication; Ubiquitin.

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Conflict of interest statement

The authors declare no competing interest.

Figures

Fig. 1
Fig. 1
The mechanisms associated with the UPS in HBV replication. The UPS modulates the replication of the HBV via the regulation of viral proteins, the viral life cycle, and innate immune response. Several components of the UPS, such as P53 and Id-1, could repress viral replication through proteasome-dependent degradation of HBV proteins, including HBx, HBc, and Pol. However, some specific proteins interact with HBV proteins to inhibit the degradation of viral proteins. The UPS participates in different steps of the viral life cycle, including the stability of cccDNA, transcription and maturation, by interacting with HBx or HBc. Many components of the UPS participate in the innate immune response to inhibit viral replication. HBV proteins, such as HBx and Pol, promote the replication of the virus via regulating the ubiquitination of proteins associated with the innate immune response. PRRs: pattern recognition receptors. ISGs: IFN stimulated genes
Fig. 2
Fig. 2
The mechanisms related to the UPS in the pathogenesis mediated by HBx. HBx could promote the development of HCC through promoting or inhibiting the functions of different components of the UPS and the ubiquitination of proteins mediated by the UPS to regulate several biological processes and molecular functions, including proliferation, apoptosis, angiogenesis, EMT, invasion, cell cycle, stem-like properties, and insulin signaling. EMT: epithelial-mesenchymal transition
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