1887

Abstract

Hepatitis B virus (HBV) infection is associated with a broad spectrum of clinical manifestations, including cirrhosis and hepatocellular carcinoma (HCC). Endoplasmic reticulum (ER) stress and subsequent oxidative stress have been implicated in liver carcinogenesis and disease progression with chronic inflammation. In our previous study, several mutations in the precore/core region of HBV genotype C were identified from 70 Korean chronic patients, and the mutations were associated with HCC and/or HBV e antigen serostatus. Here, we found that the naturally occurring mutations P5T/H/L of the HBV core antigen induced ER stress. The upregulation of ER stress resulted in higher reactive oxygen species production, intracellular calcium concentration, inflammatory cytokines as well as surface antigen production and apoptosis of cells. This study suggested that these mutations may contribute to the progression of liver disease in chronic patients.

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2015-07-01
2024-04-23
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References

  1. Ait-goughoulte M., Lucifora J., Zoulim F., Durantel D. (2010). Innate antiviral immune responses to hepatitis B virusViruses 213941410 [View Article][PubMed]. [Google Scholar]
  2. Arzumanyan A., Reis H.M.G.P.V., Feitelson M.A. (2013). Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinomaNat Rev Cancer 13123135 [View Article][PubMed]. [Google Scholar]
  3. Benali-Furet N.L., Chami M., Houel L., De Giorgi F., Vernejoul F., Lagorce D., Buscail L., Bartenschlager R., Ichas F., other authors. (2005). Hepatitis C virus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletionOncogene 2449214933 [View Article][PubMed]. [Google Scholar]
  4. Cho H.K., Cheong K.J., Kim H.Y., Cheong J. (2011). Endoplasmic reticulum stress induced by hepatitis B virus X protein enhances cyclo-oxygenase 2 expression via activating transcription factor 4Biochem J 435431439 [View Article][PubMed]. [Google Scholar]
  5. Chua P.K., Wang R.Y., Lin M.H., Masuda T., Suk F.M., Shih C. (2005). Reduced secretion of virions and hepatitis B virus (HBV) surface antigen of a naturally occurring HBV variant correlates with the accumulation of the small S envelope protein in the endoplasmic reticulum and Golgi apparatusJ Virol 791348313496 [View Article][PubMed]. [Google Scholar]
  6. Dolai S., Pal S., Yadav R.K., Adak S. (2011). Endoplasmic reticulum stress-induced apoptosis in Leishmania through Ca2+-dependent and caspase-independent mechanismJ Biol Chem 2861363813646 [View Article][PubMed]. [Google Scholar]
  7. Ganem D. (1999). Infectious avenues to cancer. In Microbes and Malignancy Infection as a Cause of Human Cancerspp. 477. Edited by J. Parsonnet. NY: Oxford University Press. [Google Scholar]
  8. Huang L.R., Wu H.L., Chen P.J., Chen D.S. (2006). An immunocompetent mouse model for the tolerance of human chronic hepatitis B virus infectionProc Natl Acad Sci U S A 1031786217867 [View Article][PubMed]. [Google Scholar]
  9. Ji C., Kaplowitz N. (2006). ER stress: can the liver cope?J Hepatol 45321333 [View Article][PubMed]. [Google Scholar]
  10. Kao J.H., Chen P.J., Lai M.Y., Chen D.S. (2002). Genotypes and clinical phenotypes of hepatitis B virus in patients with chronic hepatitis B virus infectionJ Clin Microbiol 4012071209 [View Article][PubMed]. [Google Scholar]
  11. Kim B.J. (2014). Hepatitis B virus mutations related to liver disease progression of Korean patientsWorld J Gastroenterol 20460467 [View Article][PubMed]. [Google Scholar]
  12. Kim H., Jee Y., Mun H.S., Song B.C., Park J.H., Hyun J.W., Hwang E.S., Cha C.Y., Kook Y.H., Kim B.J. (2007). Comparison of full genome sequences between two hepatitis B virus strains with or without preC mutation (A1896) from a single Korean hepatocellular carcinoma patientJ Microbiol Biotechnol 17701704[PubMed]. [Google Scholar]
  13. Kim H.J., Park J.H., Jee Y., Lee S.A., Kim H., Song B.C., Yang S., Lee M., Yoon J.H., other authors. (2008). Hepatitis B virus X mutations occurring naturally associated with clinical severity of liver disease among Korean patients with chronic genotype C infectionJ Med Virol 8013371343 [View Article][PubMed]. [Google Scholar]
  14. Kim D.W., Lee S.A., Hwang E.S., Kook Y.H., Kim B.J. (2012). Naturally occurring precore/core region mutations of hepatitis B virus genotype C related to hepatocellular carcinomaPLoS One 7e47372 [View Article][PubMed]. [Google Scholar]
  15. Kim D.W., Lee S.A., Kim H., Won Y.S., Kim B.J. (2014). Naturally occurring mutations in the nonstructural region 5B of hepatitis C virus (HCV) from treatment-naı¨ve Korean patients chronically infected with HCV genotype 1bPLoS One 9e87773 [View Article][PubMed]. [Google Scholar]
  16. Lavanchy D. (2004). Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measuresJ Viral Hepat 1197107 [View Article][PubMed]. [Google Scholar]
  17. Lavanchy D. (2005). Worldwide epidemiology of HBV infection, disease burden, and vaccine preventionJ Clin Virol 34(Suppl 1), S1S3.[CrossRef] [Google Scholar]
  18. Lee S.A., Mun H.S., Kim H., Lee H.K., Kim B.J., Hwang E.S., Kook Y.H., Kim B.J. (2011). Naturally occurring hepatitis B virus X deletions and insertions among Korean chronic patientsJ Med Virol 836570 [View Article][PubMed]. [Google Scholar]
  19. Löhr H., Goergen B., Weber W., Gödderz W., Meyer zum Büschenfelde K.H., Gerken G. (1994). Mixed cryoglobulinemia type II in chronic hepatitis B associated with HBe-minus HBV mutant: cellular immune reactions and response to interferon treatmentJ Med Virol 44330335 [View Article][PubMed]. [Google Scholar]
  20. Malhi H., Kaufman R.J. (2011). Endoplasmic reticulum stress in liver diseaseJ Hepatol 54795809 [View Article][PubMed]. [Google Scholar]
  21. Marra M., Sordelli I.M., Lombardi A., Lamberti M., Tarantino L., Giudice A., Stiuso P., Abbruzzese A., Sperlongano R., other authors. (2011). Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overviewJ Transl Med 9171 [View Article][PubMed]. [Google Scholar]
  22. Pollicino T., Cacciola I., Saffioti F., Raimondo G. (2014). Hepatitis B virus PreS/S gene variants: pathobiology and clinical implicationsJ Hepatol 61408417 [View Article][PubMed]. [Google Scholar]
  23. Safioleas M., Lygidakis N.J., Manti C. (2007). Hepatitis B todayHepatogastroenterology 54545548[PubMed]. [Google Scholar]
  24. Wang S., Kaufman R.J. (2012). The impact of the unfolded protein response on human diseaseJ Cell Biol 197857867 [View Article][PubMed]. [Google Scholar]
  25. Wang H.C., Huang W., Lai M.D., Su I.J. (2006). Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesisCancer Sci 97683688 [View Article][PubMed]. [Google Scholar]
  26. Wang J., Wang B., Huang S., Song Z., Wu J., Zhang E., Zhu Z., Zhu B., Yin Y., other authors. (2014). Immunosuppressive drugs modulate the replication of hepatitis B virus (HBV) in a hydrodynamic injection mouse modelPLoS One 9e85832 [View Article][PubMed]. [Google Scholar]
  27. Wieland S.F., Chisari F.V. (2005). Stealth and cunning: hepatitis B and hepatitis C virusesJ Virol 7993699380 [View Article][PubMed]. [Google Scholar]
  28. Xu Z., Jensen G., Yen T.S. (1997). Activation of hepatitis B virus S promoter by the viral large surface protein via induction of stress in the endoplasmic reticulumJ Virol 7173877392[PubMed]. [Google Scholar]
  29. Yang P.L., Althage A., Chung J., Chisari F.V. (2002). Hydrodynamic injection of viral DNA: a mouse model of acute hepatitis B virus infectionProc Natl Acad Sci U S A 991382513830 [View Article][PubMed]. [Google Scholar]
  30. Zhang L., Wang A. (2012). Virus-induced ER stress and the unfolded protein responseFront Plant Sci 3293 [View Article][PubMed]. [Google Scholar]
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