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Review

Naturally Occurring Hepatitis B Virus Mutations Leading to Endoplasmic Reticulum Stress and Their Contribution to the Progression of Hepatocellular Carcinoma

Department of Microbiology and Immunology, Biomedical Sciences, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Korea
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 597; https://doi.org/10.3390/ijms20030597
Received: 27 December 2018 / Revised: 23 January 2019 / Accepted: 24 January 2019 / Published: 30 January 2019
(This article belongs to the Special Issue Endoplasmic Reticulum Stress and Unfolded Protein Response)
Hepatitis B virus (HBV) infection is a global health problem that causes a wide range of pathological outcomes, including cirrhosis and hepatocellular carcinoma (HCC). Endoplasmic reticulum (ER) stress induction by HBV infection has been implicated in liver carcinogenesis and disease progression with chronic inflammation via enhanced inflammation, oxidative stress-mediated DNA damage, and hepatocyte proliferation. In the natural course of HBV infection, the accumulation of naturally occurring mutations in the HBV genome can generate several mutant types of HBV-encoded proteins, including three different proteins in the S ORF (SHBs, MHBs, and LHBs) and HBcAg in the C ORF, which could contribute to enhanced ER stress in infected hepatocytes mainly via increased ER accumulation of mutant proteins. However, it seems that there may be distinct capacity and pathway in ER stress-induction and distinct resulting clinical outcomes between HBV variants. In addition, the role of HBxAg mutations in ER stress remains unknown. However, it has been reported that HBxAg itself could exert ER stress in infected cells, resulting in HCC generation in chronic HBV patients. To date, review papers regarding ER stress-mediated HBV mutation have been limited into a specific mutation type: preS2 deletion. So, in this review, we will discuss details about various mutation types in all four regions of the HBV genome (preS1, preS2, S, and C) related to ER stress and their distinct ER stress mechanisms and clinical outcomes in terms of mutation types. View Full-Text
Keywords: Hepatitis B virus infection (HBV); Endoplasmic Reticulum stress; HBV surface antigen (HBsAg); preS/S mutations; core mutations; HBx mutations; Unfolded protein response (UPR); PERK; IRE1; ATF6; Hepatocellular carcinoma (HCC), apoptosis Hepatitis B virus infection (HBV); Endoplasmic Reticulum stress; HBV surface antigen (HBsAg); preS/S mutations; core mutations; HBx mutations; Unfolded protein response (UPR); PERK; IRE1; ATF6; Hepatocellular carcinoma (HCC), apoptosis
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MDPI and ACS Style

Choi, Y.-M.; Lee, S.-Y.; Kim, B.-J. Naturally Occurring Hepatitis B Virus Mutations Leading to Endoplasmic Reticulum Stress and Their Contribution to the Progression of Hepatocellular Carcinoma. Int. J. Mol. Sci. 2019, 20, 597. https://doi.org/10.3390/ijms20030597

AMA Style

Choi Y-M, Lee S-Y, Kim B-J. Naturally Occurring Hepatitis B Virus Mutations Leading to Endoplasmic Reticulum Stress and Their Contribution to the Progression of Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2019; 20(3):597. https://doi.org/10.3390/ijms20030597

Chicago/Turabian Style

Choi, Yu-Min, So-Young Lee, and Bum-Joon Kim. 2019. "Naturally Occurring Hepatitis B Virus Mutations Leading to Endoplasmic Reticulum Stress and Their Contribution to the Progression of Hepatocellular Carcinoma" International Journal of Molecular Sciences 20, no. 3: 597. https://doi.org/10.3390/ijms20030597

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