AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
PDF (3.5 MB)
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Full Length Article | Open Access

The proteasome activator subunit PSME1 promotes HBV replication by inhibiting the degradation of HBV core protein

Yu LiuaJiaxin YangaYanyan WangaQiqi ZengaYao FanbAilong Huanga( )Hui Fana( )
The Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China
The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China

Peer review under responsibility of Chongqing Medical University.

Show Author Information

Abstract

Chronic hepatitis B virus (HBV) infection is a leading cause of liver cirrhosis and hepatocellular carcinoma, representing a global health problem for which a functional cure is difficult to achieve. The HBV core protein (HBc) is essential for multiple steps in the viral life cycle. It is the building block of the nucleocapsid in which viral DNA reverse transcription occurs, and its mediation role in viral-host cell interactions is critical to HBV infection persistence. However, systematic studies targeting HBc-interacting proteins remain lacking. Here, we combined HBc with the APEX2 to systematically identify HBc-related host proteins in living cells. Using functional screening, we confirmed that proteasome activator subunit 1 (PSME1) is a potent HBV-associated host factor. PSME1 expression was up-regulated upon HBV infection, and the protein level of HBc decreased after PSME1 knockdown. Mechanistically, the interaction between PSME1 and HBc inhibited the degradation of HBc by the 26S proteasome, thereby improving the stability of the HBc protein. Furthermore, PSME1 silencing inhibits HBV transcription in the HBV infection system. Our findings reveal an important mechanism by which PSME1 regulates HBc proteins and may facilitate the development of new antiviral therapies targeting PSME1 function.

References

1

Fung S, Choi HSJ, Gehring A, Janssen HLA. Getting to HBV cure: the promising paths forward. Hepatology. 2022;76(1):233–250.

2

Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev. 2000;64(1):51–68.

3

Shih C, Yang CC, Choijilsuren G, Chang CH, Liou AT. Hepatitis B virus. Trends Microbiol. 2018;26(4):386–387.

4

Collaborators PO. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018;3(6):383–403.

5

Jeng WJ, Papatheodoridis GV, Lok ASF. Hepatitis B. Lancet. 2023;401(10381):1039–1052.

6

Neuveut C, Wei Y, Buendia MA. Mechanisms of HBV-related hepatocarcinogenesis. J Hepatol. 2010;52(4):594–604.

7

Lok J, Dusheiko G, Carey I, Agarwal K. Review article: novel biomarkers in hepatitis B infection. Aliment Pharmacol Ther. 2022;56(5):760–776.

8

Nassal M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015;64(12):1972–1984.

9

Ryu DK, Ahn BY, Ryu WS. Proximity between the cap and 5′ epsilon stem-loop structure is critical for the suppression of pgRNA translation by the hepatitis B viral polymerase. Virology. 2010;406(1):56–64.

10

Ryu DK, Kim S, Ryu WS. Hepatitis B virus polymerase suppresses translation of pregenomic RNA via a mechanism involving its interaction with 5′ stem-loop structure. Virology. 2008;373(1):112–123.

11

Nassal M. The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly. J Virol. 1992;66(7):4107–4116.

12

Selzer L, Kant R, Wang JC, Bothner B, Zlotnick A. Hepatitis B virus core protein phosphorylation sites affect capsid stability and transient exposure of the C-terminal domain. J Biol Chem. 2015;290(47):28584–28593.

13

Basagoudanavar SH, Perlman DH, Hu J. Regulation of hepadnavirus reverse transcription by dynamic nucleocapsid phosphorylation. J Virol. 2007;81(4):1641–1649.

14

Diab A, Foca A, Zoulim F, Durantel D, Andrisani O. The diverse functions of the hepatitis B core/capsid protein (HBc) in the viral life cycle: implications for the development of HBc-targeting antivirals. Antivir Res. 2018;149:211–220.

15

Rabe B, Vlachou A, Panté N, Helenius A, Kann M. Nuclear import of hepatitis B virus capsids and release of the viral genome. Proc Natl Acad Sci USA. 2003;100(17):9849–9854.

16

Martinez MG, Boyd A, Combe E, Testoni B, Zoulim F. Covalently closed circular DNA: the ultimate therapeutic target for curing HBV infections. J Hepatol. 2021;75(3):706–717.

17

Hung V, Udeshi ND, Lam SS, et al. Spatially resolved proteomic mapping in living cells with the engineered peroxidase APEX2. Nat Protoc. 2016;11(3):456–475.

18

Ke M, Yuan X, He A, et al. Spatiotemporal profiling of cytosolic signaling complexes in living cells by selective proximity proteomics. Nat Commun. 2021;12(1):71.

19

Lam SS, Martell JD, Kamer KJ, et al. Directed evolution of APEX2 for electron microscopy and proximity labeling. Nat Methods. 2015;12(1):51–54.

20

Zhou Y, Wang G, Wang P, et al. Expanding APEX2 substrates for proximity-dependent labeling of nucleic acids and proteins in living cells. Angew Chem Int Ed Engl. 2019;58(34):11763–11767.

21

Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002;82(2):373–428.

22

Sijts EJAM, Kloetzel PM. The role of the proteasome in the generation of MHC class I ligands and immune responses. Cell Mol Life Sci. 2011;68(9):1491–1502.

23

de Graaf N, van Helden MJG, Textoris-Taube K, et al. PA28 and the proteasome immunosubunits play a central and independent role in the production of MHC class I-binding peptides in vivo. Eur J Immunol. 2011;41(4):926–935.

24

Ma CP, Slaughter CA, DeMartino GN. Identification, purification, and characterization of a protein activator (PA28) of the 20 S proteasome (macropain). J Biol Chem. 1992;267(15):10515–10523.

25

Sánchez-Martín D, Martínez-Torrecuadrada J, Teesalu T, et al. Proteasome activator complex PA28 identified as an accessible target in prostate cancer by in vivo selection of human antibodies. Proc Natl Acad Sci USA. 2013;110(34):13791–13796.

26

Feng X, Jiang Y, Xie L, et al. Overexpression of proteasomal activator PA28α serves as a prognostic factor in oral squamous cell carcinoma. J Exp Clin Cancer Res. 2016;35:35.

27

Gu Y, Barwick BG, Shanmugam M, et al. Downregulation of PA28α induces proteasome remodeling and results in resistance to proteasome inhibitors in multiple myeloma. Blood Cancer J. 2020;10:125.

28

Vasuri F, Capizzi E, Bellavista E, et al. Studies on immunoproteasome in human liver. Part I: absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis. Biochem Biophys Res Commun. 2010;397(2):301–306.

29

Xun Z, Yao X, Zhu C, et al. Proteomic characterization of the natural history of chronic HBV infection revealed by tandem mass tag-based quantitative proteomics approach. Mater Today Bio. 2022;15:100302.

30

Fan Y, Liang Y, Liu Y, Fan H. PRKDC promotes hepatitis B virus transcription through enhancing the binding of RNA Pol II to cccDNA. Cell Death Dis. 2022;13:404.

31

Miller KE, Kim Y, Huh WK, Park HO. Bimolecular fluorescence complementation (BiFC) analysis: advances and recent applications for genome-wide interaction studies. J Mol Biol. 2015;427(11):2039–2055.

32

Kodama Y, Hu CD. Bimolecular fluorescence complementation (BiFC): a 5-year update and future perspectives. Biotechniques. 2012;53(5):285–298.

33

Kerppola TK. Bimolecular fluorescence complementation (BiFC) analysis as a probe of protein interactions in living cells. Annu Rev Biophys. 2008;37:465–487.

34

Shen J, Zhang W, Gan C, et al. Strategies to improve the fluorescent signal of the tripartite sfGFP system. Acta Biochim Biophys Sin. 2020;52(9):998–1006.

35

Zlotnick A, Venkatakrishnan B, Tan Z, Lewellyn E, Turner W, Francis S. Core protein: a pleiotropic keystone in the HBV lifecycle. Antivir Res. 2015;121:82–93.

36

Ludgate L, Liu K, Luckenbaugh L, et al. Cell-free hepatitis B virus capsid assembly dependent on the core protein C-terminal domain and regulated by phosphorylation. J Virol. 2016;90(12):5830–5844.

37

Liu K, Luckenbaugh L, Ning X, Xi J, Hu J. Multiple roles of core protein linker in hepatitis B virus replication. PLoS Pathog. 2018;14(5):e1007085.

38

Shi Y, Zheng M. Hepatitis B virus persistence and reactivation. BMJ. 2020;370:m2200.

39

Lamontagne J, Mell JC, Bouchard MJ. Transcriptome-wide analysis of hepatitis B virus-mediated changes to normal hepatocyte gene expression. PLoS Pathog. 2016;12(2):e1005438.

40

Yuan S, Liao G, Zhang M, et al. Translatomic profiling reveals novel self-restricting virus-host interactions during HBV infection. J Hepatol. 2021;75(1):74–85.

41

Xie Q, Fan F, Wei W, et al. Multi-omics analyses reveal metabolic alterations regulated by hepatitis B virus core protein in hepatocellular carcinoma cells. Sci Rep. 2017;7:41089.

42

Chabrolles H, Auclair H, Vegna S, et al. Hepatitis B virus core protein nuclear interactome identifies SRSF10 as a host RNA-binding protein restricting HBV RNA production. PLoS Pathog. 2020;16(11):e1008593.

43

Al-Mozaini M, Alzahrani A, Alsharif I, et al. Quantitative proteomics analysis reveals unique but overlapping protein signatures in HIV infections. J Infect Public Health. 2021;14(6):795–802.

44

Respondek D, Voss M, Kühlewindt I, Klingel K, Krüger E, Beling A. PA28 modulates antigen processing and viral replication during coxsackievirus B3 infection. PLoS One. 2017;12(3):e0173259.

45

Makjaroen J, Somparn P, Hodge K, Poomipak W, Hirankarn N, Pisitkun T. Comprehensive proteomics identification of IFN-λ3-regulated antiviral proteins in HBV-transfected cells. Mol Cell Proteomics. 2018;17(11):2197–2215.

46

Osna NA, White RL, Krutik VM, Wang T, Weinman SA, Donohue TM. Proteasome activation by hepatitis C core protein is reversed by ethanol-induced oxidative stress. Gastroenterology. 2008;134(7):2144–2152.

47

Zhang D, Lim SG, Koay ES. Proteomic identification of down-regulation of oncoprotein DJ-1 and proteasome activator subunit 1 in hepatitis B virus-infected well-differentiated hepatocellular carcinoma. Int J Oncol. 2007;31(3):577–584.

48

Schaaf MBE, Keulers TG, Vooijs MA, Rouschop KMA. LC3/GABARAP family proteins: autophagy-(un)related functions. FASEB J. 2016;30(12):3961–3978.

Genes & Diseases
Article number: 101142
Cite this article:
Liu Y, Yang J, Wang Y, et al. The proteasome activator subunit PSME1 promotes HBV replication by inhibiting the degradation of HBV core protein. Genes & Diseases, 2024, 11(6): 101142. https://doi.org/10.1016/j.gendis.2023.101142

42

Views

0

Downloads

0

Crossref

0

Web of Science

1

Scopus

0

CSCD

Altmetrics

Received: 15 April 2023
Revised: 27 August 2023
Accepted: 10 September 2023
Published: 14 October 2023
© 2023 The Authors.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Return