Possible Involvement of Multidrug-Resistant Hepatitis B Virus sW172* Truncation Variant in the ER Stress Signaling Pathway during Hepatocarcinogenesis
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- Zheng Jiajia
- Department of Laboratory Medicine, Peking University Third Hospital Centers for the Infectious Disease & the Department of Microbiology, Peking University Health Science Center
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- Jiang Suzhen
- Department of Infectious Disease, Peking University International Hospital
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- Lu Fengmin
- Centers for the Infectious Disease & the Department of Microbiology, Peking University Health Science Center
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We investigated the biological effect of hepatitis B virus (HBV) rtA181T/sW172* point mutation on HBsAg secretion and the potential mechanisms involved in hepatocarcinogenesis. Full-length HBV wild type (wt) and HBV rtA181T/sW172* expression plasmids were transfected into HepG2 cell lines or were injected into C57BL/6 mice. The extracellular and intracellular expression levels of HBsAg and HBeAg proteins, in mouse serum and liver tissues were detected by ELISA. The localization of the truncated protein was characterized in vitro. The mRNA expression of endoplasmic reticulum (ER) stress gene GRP78 was determined. HBsAg levels were significantly higher in both supernatant of cells transfected with HBV wt and serum of mice injected with HBV wt, compared with that of HBV rtA181T/sW172* mutant. The reversed trend was observed in intracellular cells and intrahepatic liver cells. Wild type S protein alone could rescue this dysfunction. HBV rtA181T/sW172* truncated surface proteins showed a more aggregated cytoplasmic pattern which were also localized to the ER in comparison with HBV wt. Furthermore, GRP78 mRNA expression was increased 72 h post-transfection in HBV rtA181T/sW172* cells relative to HBV wt cells (P = 0.0154). The HBV sW172* truncation variant has a defect on HBsAg secretion which can lead to surface protein retention in the ER, where it may contribute to hepatocarcinogenesis through activating the ER stress signaling pathway.
収録刊行物
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- Japanese Journal of Infectious Diseases
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Japanese Journal of Infectious Diseases 69 (4), 306-313, 2016
国立感染症研究所 Japanese Journal of Infectious Diseases 編集委員会
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詳細情報 詳細情報について
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- CRID
- 1390282681217530368
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- NII論文ID
- 130005165474
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- NII書誌ID
- AA1132885X
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- ISSN
- 18842836
- 13446304
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- NDL書誌ID
- 027506909
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- PubMed
- 26567840
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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