Crosstalk Between Hepatitis B Virus X and High-mobility Group Box 1 Facilitates Autophagy in Hepatocytes

Overview

Journal Mol Oncol

Specialties Molecular Biology
Oncology

Date 2018 Jan 10

PMID 29316268

Citations 24

Authors

Sha Fu

Juan Wang

Xingwang Hu

Rong-Rong Zhou

Yongming Fu

Daolin Tang

Rui Kang

Yan Huang

Lunquan Sun

Ning Li

Xue-Gong Fan

Affiliations

Soon will be listed here.

Abstract

Hepatitis B virus (HBV) X (HBx) protein is a pivotal regulator of HBV-triggered autophagy. However, the role of HBx-induced epigenetic changes in autophagy remains largely unknown. The cytoplasmic (Cyt) high-mobility group box 1 (HMGB1) has been identified as a positive regulator of autophagy, and its Cyt translocation is closely associated with its acetylation status. Here, we evaluated the function of HMGB1 in HBx-mediated autophagy and its association with histone deacetylase (HDAC). Using cell lines with enforced expression of HBx, we demonstrated that HBx upregulated the expression of HMGB1 and promoted its Cyt translocation by acetylation to facilitate autophagy. We further identified the underlying mechanism by which decreased nuclear HDAC activity and expression levels contribute to the HBx-promoted hyperacetylation and subsequent translocation of HMGB1. We also identified the HDAC1 isoform as a critical factor in regulating this phenomenon. In addition, HBx bound to HMGB1 in the cytoplasm, which triggered autophagy in hepatocytes. Pharmacological inhibition of HMGB1 Cyt translocation with ethyl pyruvate prevented HBx-induced autophagy. These results demonstrate a novel function of acetylated HMGB1 in HBx-mediated autophagy in hepatocytes.

Citing Articles

HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma.

Li Y, Wang F, Geng Z, He T, Song Y, Wu J Cell Biosci. 2024; 14(1):116.

PMID: 39256879 PMC: 11389268. DOI: 10.1186/s13578-024-01298-2.

N-terminal domain of classical swine fever virus N induces proteasomal degradation of specificity protein 1 with reduced HDAC1 expression to evade from innate immune responses.

Chen R, Han X, Xu H, Xu J, Cao T, Shan Y J Virol. 2023; 97(10):e0111523.

PMID: 37796122 PMC: 10617410. DOI: 10.1128/jvi.01115-23.

Patho-epigenetics: histone deacetylases as targets of pathogens and therapeutics.

Schator D, Gomez-Valero L, Buchrieser C, Rolando M Microlife. 2023; 2:uqab013.

PMID: 37223249 PMC: 10117728. DOI: 10.1093/femsml/uqab013.

Micro-PET imaging of hepatitis C virus NS3/4A protease activity using a protease-activatable retention probe.

Chuang C, Cheng T, Chen W, Huang Y, Wang H, Lo Y Front Microbiol. 2022; 13:896588.

PMID: 36406412 PMC: 9672079. DOI: 10.3389/fmicb.2022.896588.

Endothelial Dysfunction, HMGB1, and Dengue: An Enigma to Solve.

Calderon-Pelaez M, Coronel-Ruiz C, Castellanos J, Velandia-Romero M Viruses. 2022; 14(8).

PMID: 36016387 PMC: 9414358. DOI: 10.3390/v14081765.

References

Bonaldi T, Talamo F, Scaffidi P, Ferrera D, Porto A, Bachi A . Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J. 2003; 22(20):5551-60. PMC: 213771. DOI: 10.1093/emboj/cdg516. View

Barqasho B, Nowak P, Abdurahman S, Walther-Jallow L, Sonnerborg A . Implications of the release of high-mobility group box 1 protein from dying cells during human immunodeficiency virus type 1 infection in vitro. J Gen Virol. 2010; 91(Pt 7):1800-9. DOI: 10.1099/vir.0.016915-0. View

Moisy D, Avilov S, Jacob Y, Laoide B, Ge X, Baudin F . HMGB1 protein binds to influenza virus nucleoprotein and promotes viral replication. J Virol. 2012; 86(17):9122-33. PMC: 3416134. DOI: 10.1128/JVI.00789-12. View

Huebener P, Gwak G, Pradere J, Quinzii C, Friedman R, Lin C . High-mobility group box 1 is dispensable for autophagy, mitochondrial quality control, and organ function in vivo. Cell Metab. 2014; 19(3):539-47. PMC: 4099361. DOI: 10.1016/j.cmet.2014.01.014. View

Pandey V, Kumar V . Stabilization of SIRT7 deacetylase by viral oncoprotein HBx leads to inhibition of growth restrictive RPS7 gene and facilitates cellular transformation. Sci Rep. 2015; 5:14806. PMC: 4595800. DOI: 10.1038/srep14806. View

Zhang G, Kobayashi T, Kamitani W, Komoto S, Yamashita M, Baba S . Borna disease virus phosphoprotein represses p53-mediated transcriptional activity by interference with HMGB1. J Virol. 2003; 77(22):12243-51. PMC: 254253. DOI: 10.1128/jvi.77.22.12243-12251.2003. View

Yoo Y, Na T, Seo H, Seong J, Park C, Shin Y . Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells. Oncogene. 2008; 27(24):3405-13. DOI: 10.1038/sj.onc.1211000. View

Belloni L, Pollicino T, De Nicola F, Guerrieri F, Raffa G, Fanciulli M . Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. Proc Natl Acad Sci U S A. 2009; 106(47):19975-9. PMC: 2775998. DOI: 10.1073/pnas.0908365106. View

Humphrey G, Wang Y, Russanova V, Hirai T, Qin J, Nakatani Y . Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1. J Biol Chem. 2000; 276(9):6817-24. DOI: 10.1074/jbc.M007372200. View

10.

Sir D, Ann D, Ou J . Autophagy by hepatitis B virus and for hepatitis B virus. Autophagy. 2010; 6(4):548-9. DOI: 10.4161/auto.6.4.11669. View

11.

Levrero M, Zucman-Rossi J . Mechanisms of HBV-induced hepatocellular carcinoma. J Hepatol. 2016; 64(1 Suppl):S84-S101. DOI: 10.1016/j.jhep.2016.02.021. View

12.

Ulloa L, Ochani M, Yang H, Tanovic M, Halperin D, Yang R . Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc Natl Acad Sci U S A. 2002; 99(19):12351-6. PMC: 129448. DOI: 10.1073/pnas.192222999. View

13.

Schuettengruber B, Simboeck E, Khier H, Seiser C . Autoregulation of mouse histone deacetylase 1 expression. Mol Cell Biol. 2003; 23(19):6993-7004. PMC: 193942. DOI: 10.1128/MCB.23.19.6993-7004.2003. View

14.

Chen S, Dong Z, Yang P, Wang X, Jin G, Yu H . Hepatitis B virus X protein stimulates high mobility group box 1 secretion and enhances hepatocellular carcinoma metastasis. Cancer Lett. 2017; 394:22-32. DOI: 10.1016/j.canlet.2017.02.011. View

15.

Rautou P, Mansouri A, Lebrec D, Durand F, Valla D, Moreau R . Autophagy in liver diseases. J Hepatol. 2010; 53(6):1123-34. DOI: 10.1016/j.jhep.2010.07.006. View

16.

Huang H, Nace G, McDonald K, Tai S, Klune J, Rosborough B . Hepatocyte-specific high-mobility group box 1 deletion worsens the injury in liver ischemia/reperfusion: a role for intracellular high-mobility group box 1 in cellular protection. Hepatology. 2013; 59(5):1984-1997. PMC: 3999251. DOI: 10.1002/hep.26976. View

17.

Sengupta N, Seto E . Regulation of histone deacetylase activities. J Cell Biochem. 2004; 93(1):57-67. DOI: 10.1002/jcb.20179. View

18.

Tang D, Kang R, Livesey K, Cheh C, Farkas A, Loughran P . Endogenous HMGB1 regulates autophagy. J Cell Biol. 2010; 190(5):881-92. PMC: 2935581. DOI: 10.1083/jcb.200911078. View

19.

Kamau E, Takhampunya R, Li T, Kelly E, Peachman K, Lynch J . Dengue virus infection promotes translocation of high mobility group box 1 protein from the nucleus to the cytosol in dendritic cells, upregulates cytokine production and modulates virus replication. J Gen Virol. 2009; 90(Pt 8):1827-1835. DOI: 10.1099/vir.0.009027-0. View

20.

Riviere L, Gerossier L, Ducroux A, Dion S, Deng Q, Michel M . HBx relieves chromatin-mediated transcriptional repression of hepatitis B viral cccDNA involving SETDB1 histone methyltransferase. J Hepatol. 2015; 63(5):1093-102. DOI: 10.1016/j.jhep.2015.06.023. View