Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway

A growing body of evidence has shown that hepatitis B surface antigen (HBsAg) mutations can influence the occurrence of occult hepatitis B infection (OBI), particularly amino acid substitutions in small hepatitis B surface proteins (SHBs). The mechanistic basis for these results, however, remains un...

Full description

Saved in:
Bibliographic Details
Main Authors: Huang Chengrong, Zhang Hao, Wang Jing, Li Jianfei, Liu Qian, Zong Qiyin, Zhang Yunyun, Wang Qin, Zhou Qiang
Format: Article
Language:English
Published: De Gruyter 2025-02-01
Series:Open Life Sciences
Subjects:
Online Access:https://doi.org/10.1515/biol-2022-0951
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1823860472125849600
author Huang Chengrong
Zhang Hao
Wang Jing
Li Jianfei
Liu Qian
Zong Qiyin
Zhang Yunyun
Wang Qin
Zhou Qiang
author_facet Huang Chengrong
Zhang Hao
Wang Jing
Li Jianfei
Liu Qian
Zong Qiyin
Zhang Yunyun
Wang Qin
Zhou Qiang
author_sort Huang Chengrong
collection DOAJ
description A growing body of evidence has shown that hepatitis B surface antigen (HBsAg) mutations can influence the occurrence of occult hepatitis B infection (OBI), particularly amino acid substitutions in small hepatitis B surface proteins (SHBs). The mechanistic basis for these results, however, remains unclear. This study was designed to explore the potential impact and mechanisms of OBI-related SHBs mutations on serum HBsAg. Huh7 and HepG2 cells were transfected with plasmids encoding wild-type (WT) or OBI-related SHB mutation-containing sequences, after which a chemiluminescence approach was used to detect HBsAg levels in cell culture supernatants. Western blotting was further used to assess HBsAg and endoplasmic reticulum stress (ERS)-related protein levels in lysates prepared from these cells, while the localization of HBsAg within cells was assessed via immunofluorescent staining. Cells transfected with OBI-related SHB mutation-encoding plasmids exhibited lower supernatant HBsAg levels than cells transfected with WT plasmids. Intracellular and extracellular HBsAg levels in these mutant plasmid-transfected cells were lower relative to those for WT plasmid-transfected cells, and HBsAg accumulation within the ER was detected via immunofluorescent staining in cells transfected with OBI-related SHB mutation-encoding plasmids, ERS-related protein content was also significantly increased in mutant plasmid-transfected cells as compared to those in the WT group. These results suggest that proteins harboring OBI-related mutations may tend to accumulate in the ER, thereby triggering an ERS response and impairing the transcription and translation of HBsAg via the activation of the unfolded protein response and ER-associated protein degradation pathway. These effects ultimately reduce the overall assembly of HBV virions in the ER and their associated secretion.
format Article
id doaj-art-07f87b96dea142d79bc2f5ae224c72fd
institution Kabale University
issn 2391-5412
language English
publishDate 2025-02-01
publisher De Gruyter
record_format Article
series Open Life Sciences
spelling doaj-art-07f87b96dea142d79bc2f5ae224c72fd2025-02-10T13:24:08ZengDe GruyterOpen Life Sciences2391-54122025-02-0120139740810.1515/biol-2022-0951Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathwayHuang Chengrong0Zhang Hao1Wang Jing2Li Jianfei3Liu Qian4Zong Qiyin5Zhang Yunyun6Wang Qin7Zhou Qiang8Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, ChinaDepartment of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, ChinaDepartment of Clinical Laboratory, Nanjing Jiangning Hospital, Nanjing, 211100, ChinaDepartment of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, ChinaDepartment of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, ChinaDepartment of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, ChinaDepartment of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, ChinaDepartment of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, ChinaDepartment of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, ChinaA growing body of evidence has shown that hepatitis B surface antigen (HBsAg) mutations can influence the occurrence of occult hepatitis B infection (OBI), particularly amino acid substitutions in small hepatitis B surface proteins (SHBs). The mechanistic basis for these results, however, remains unclear. This study was designed to explore the potential impact and mechanisms of OBI-related SHBs mutations on serum HBsAg. Huh7 and HepG2 cells were transfected with plasmids encoding wild-type (WT) or OBI-related SHB mutation-containing sequences, after which a chemiluminescence approach was used to detect HBsAg levels in cell culture supernatants. Western blotting was further used to assess HBsAg and endoplasmic reticulum stress (ERS)-related protein levels in lysates prepared from these cells, while the localization of HBsAg within cells was assessed via immunofluorescent staining. Cells transfected with OBI-related SHB mutation-encoding plasmids exhibited lower supernatant HBsAg levels than cells transfected with WT plasmids. Intracellular and extracellular HBsAg levels in these mutant plasmid-transfected cells were lower relative to those for WT plasmid-transfected cells, and HBsAg accumulation within the ER was detected via immunofluorescent staining in cells transfected with OBI-related SHB mutation-encoding plasmids, ERS-related protein content was also significantly increased in mutant plasmid-transfected cells as compared to those in the WT group. These results suggest that proteins harboring OBI-related mutations may tend to accumulate in the ER, thereby triggering an ERS response and impairing the transcription and translation of HBsAg via the activation of the unfolded protein response and ER-associated protein degradation pathway. These effects ultimately reduce the overall assembly of HBV virions in the ER and their associated secretion.https://doi.org/10.1515/biol-2022-0951occult hepatitis b virus infectionhepatitis b surface antigenmutationendoplasmic reticulum stresser-associated protein degradation
spellingShingle Huang Chengrong
Zhang Hao
Wang Jing
Li Jianfei
Liu Qian
Zong Qiyin
Zhang Yunyun
Wang Qin
Zhou Qiang
Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
Open Life Sciences
occult hepatitis b virus infection
hepatitis b surface antigen
mutation
endoplasmic reticulum stress
er-associated protein degradation
title Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
title_full Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
title_fullStr Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
title_full_unstemmed Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
title_short Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
title_sort preliminary analysis of the role of small hepatitis b surface proteins mutations in the pathogenesis of occult hepatitis b infection via the endoplasmic reticulum stress induced upr erad pathway
topic occult hepatitis b virus infection
hepatitis b surface antigen
mutation
endoplasmic reticulum stress
er-associated protein degradation
url https://doi.org/10.1515/biol-2022-0951
work_keys_str_mv AT huangchengrong preliminaryanalysisoftheroleofsmallhepatitisbsurfaceproteinsmutationsinthepathogenesisofocculthepatitisbinfectionviatheendoplasmicreticulumstressinducedupreradpathway
AT zhanghao preliminaryanalysisoftheroleofsmallhepatitisbsurfaceproteinsmutationsinthepathogenesisofocculthepatitisbinfectionviatheendoplasmicreticulumstressinducedupreradpathway
AT wangjing preliminaryanalysisoftheroleofsmallhepatitisbsurfaceproteinsmutationsinthepathogenesisofocculthepatitisbinfectionviatheendoplasmicreticulumstressinducedupreradpathway
AT lijianfei preliminaryanalysisoftheroleofsmallhepatitisbsurfaceproteinsmutationsinthepathogenesisofocculthepatitisbinfectionviatheendoplasmicreticulumstressinducedupreradpathway
AT liuqian preliminaryanalysisoftheroleofsmallhepatitisbsurfaceproteinsmutationsinthepathogenesisofocculthepatitisbinfectionviatheendoplasmicreticulumstressinducedupreradpathway
AT zongqiyin preliminaryanalysisoftheroleofsmallhepatitisbsurfaceproteinsmutationsinthepathogenesisofocculthepatitisbinfectionviatheendoplasmicreticulumstressinducedupreradpathway
AT zhangyunyun preliminaryanalysisoftheroleofsmallhepatitisbsurfaceproteinsmutationsinthepathogenesisofocculthepatitisbinfectionviatheendoplasmicreticulumstressinducedupreradpathway
AT wangqin preliminaryanalysisoftheroleofsmallhepatitisbsurfaceproteinsmutationsinthepathogenesisofocculthepatitisbinfectionviatheendoplasmicreticulumstressinducedupreradpathway
AT zhouqiang preliminaryanalysisoftheroleofsmallhepatitisbsurfaceproteinsmutationsinthepathogenesisofocculthepatitisbinfectionviatheendoplasmicreticulumstressinducedupreradpathway