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.

IF 1.7 4区 生物学 Q3 BIOLOGY
Open Life Sciences Pub Date : 2025-02-04 eCollection Date: 2025-01-01 DOI:10.1515/biol-2022-0951
Chengrong Huang, Hao Zhang, Jing Wang, Jianfei Li, Qian Liu, Qiyin Zong, Yunyun Zhang, Qin Wang, Qiang Zhou
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引用次数: 0

Abstract

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.

乙型肝炎表面小蛋白突变在内质网应激诱导的UPR-ERAD通路隐性乙型肝炎感染发病机制中的作用初步分析
越来越多的证据表明,乙型肝炎表面抗原(HBsAg)突变可影响隐性乙型肝炎感染(OBI)的发生,特别是乙型肝炎表面小蛋白(SHBs)的氨基酸取代。然而,这些结果的机制基础仍不清楚。本研究旨在探讨obi相关SHBs突变对血清HBsAg的潜在影响及其机制。用编码野生型(WT)或obi相关SHB突变序列的质粒转染Huh7和HepG2细胞,然后用化学发光法检测细胞培养上清液中的HBsAg水平。Western blotting进一步用于评估这些细胞制备的裂解物中HBsAg和内质网应激(ERS)相关蛋白水平,同时通过免疫荧光染色评估细胞内HBsAg的定位。转染obi相关SHB突变编码质粒的细胞上清HBsAg水平低于转染WT质粒的细胞。与WT质粒转染的细胞相比,这些突变质粒转染的细胞内和细胞外HBsAg水平较低,并且通过免疫荧光染色检测了obi相关SHB突变编码质粒转染的细胞内质网内HBsAg积累,与WT组相比,突变质粒转染的细胞中ers相关蛋白含量也显著增加。这些结果表明,携带obi相关突变的蛋白可能倾向于在内质网中积累,从而触发内质网反应,并通过激活未折叠蛋白反应和内质网相关蛋白降解途径损害HBsAg的转录和翻译。这些作用最终减少了HBV病毒粒子在内质网中的总体组装及其相关分泌。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.50
自引率
4.50%
发文量
131
审稿时长
43 weeks
期刊介绍: Open Life Sciences (previously Central European Journal of Biology) is a fast growing peer-reviewed journal, devoted to scholarly research in all areas of life sciences, such as molecular biology, plant science, biotechnology, cell biology, biochemistry, biophysics, microbiology and virology, ecology, differentiation and development, genetics and many others. Open Life Sciences assures top quality of published data through critical peer review and editorial involvement throughout the whole publication process. Thanks to the Open Access model of publishing, it also offers unrestricted access to published articles for all users.
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