Hepatitis B spliced protein (HBSP) generated by a spliced hepatitis B virus RNA participates in abnormality of fibrin formation and functions by binding to fibrinogen γ chain

Chen, Jinyan; Chen, Wan-Nan; Liu, Lingling; Lin, Wei; Jiao, Bo-Yan; Wu, Yunli; Lin, Jianghai; Lin, Xu

doi:10.1002/jmv.21918

Cited by 19 publications

(18 citation statements)

References 21 publications

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“…In our previous study, we searched for novel HBSP binding partners by yeast two-hybrid assay using HBSP as bait to screen a human liver cDNA library and succeeded in identifying CTSB as 1 of 20 HBSP-binding candidates (8). In the present study, we performed comprehensive studies to confirm the interaction of HBSP with CTSB.…”

Section: Discussionmentioning

confidence: 92%

“…A 2.2-kb spliced, defective HBV DNA was previously isolated from a patient with chronic HBV infection (8). The CTSB and cathepsin D (CTSD) genes were reverse transcribed from the total RNA isolated from Huh-7 cells and cloned into pCMVTNT at the XhoI and SalI sites of the vector (Promega, Madison, WI).…”

Section: Methodsmentioning

confidence: 99%

“…Construction, expression, and purification of glutathione S-transferase (GST)-fused HBSP or HBx were described previously (8,12). An in vitro T7-coupled reticulocyte lysate system (Promega) was used to generate 35 S-labeled CTSB protein by the addition of 2 g of pCMVTNT-CTSB with 50 Ci of […”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown the evidence of interaction between HBSP and CTSB in a yeast two-hybrid system (8). To test the association between these two proteins in vitro, we carried out a GST pulldown assay.…”

Section: Hbsp Enhances the Invasion And Migration Of Hepatoma Cellsmentioning

confidence: 99%

“…We previously showed that cathepsin B (CTSB) was one of the major intracellular interacting partners of HBSP, and it was identified using a yeast two-hybrid screening assay (8). This led us to investigate whether the HBSP could interact with CTSB in the context of hepatoma cells to affect cell migration, invasion, and metastasis, all of which can be modulated by CTSB acting directly and indirectly on extracellular matrix (ECM) component remodeling and degradation (26,47).…”

mentioning

confidence: 99%

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Interaction of the Hepatitis B Spliced Protein with Cathepsin B Promotes Hepatoma Cell Migration and Invasion

Chen

Jiao

et al. 2012

J Virol

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C hronic hepatitis B virus (HBV) infection has been proven to be one of the most important risk factors for the development of hepatocellular carcinoma (HCC) (3, 9). However, the pathogenesis of cancer in HBV infection is still not fully understood, and it appears that multiple factors and cellular signaling pathways are involved in hepatocarcinogenesis (28). Integration of HBV genome into host DNA can lead to alterations in cellular gene function or generate chromosomal instability (1, 10, 43). Expression of some oncogenic HBV proteins such as HBx and truncated Pre-S2/S has been shown to have a direct effect on malignant transformation of the liver (42) and to promote metastasis of the malignant cells, and there is thus a very high mortality rate for HCC patients (18). Another HBV protein, encoded by a singly spliced 2.2-kb HBV DNA and referred to as the hepatitis B spliced protein (HBSP), is found to be expressed in liver biopsy tissues from four out of five chronic patients but not from two hepatitis C virus-infected patient samples and one normal liver sample (39). Our prior study also showed that a 2.2-kb splice variant was present in all tumor and peritumor samples from 12 HCC patients studied (20). Exogenous expression of HBSP in transfected Huh-7 cells can induce cell apoptosis (40). However, the cytopathic effect of the HBSP was unclear, and its role in progression, invasion, and metastasis of HBV-related HCC has not yet been elucidated.We previously showed that cathepsin B (CTSB) was one of the major intracellular interacting partners of HBSP, and it was identified using a yeast two-hybrid screening assay (8). This led us to investigate whether the HBSP could interact with CTSB in the context of hepatoma cells to affect cell migration, invasion, and metastasis, all of which can be modulated by CTSB acting directly and indirectly on extracellular matrix (ECM) component remodeling and degradation (26,47). CTSB is a lysosomal cysteine protease that plays an important role in physiological protein turnover and processing (19,41). In nonmalignant cells, CTSB is mainly stored in the lysosome, whereas in malignant cells, CTSB redistributes into exocytic vesicles at the cell periphery, leading to its secretion and association with binding partners on the tumor cell surface (22,33). CTSB can cleave and activate a wide variety of substrates in proteolytic pathways that increase neoplastic progression. It has been shown that activation of urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs) by CTSB not only enhances ECM degradation and cancer cell motility and invasion (14) but also induces in vitro angiogenesis (2). In addition to interacting with other proteases, CTSB may regulate the activity of kinase signaling networks, cell surface receptors, and signaling molecules such as chemokines, cytokines and growth factors (25). However, such interactions are usually bidirectional because kinases can also regulate many proteases through phosphorylation while proteases can control the actio...

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Section: Discussionmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Hbsp Enhances the Invasion And Migration Of Hepatoma Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

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Interaction of the Hepatitis B Spliced Protein with Cathepsin B Promotes Hepatoma Cell Migration and Invasion

Chen

Jiao

et al. 2012

J Virol

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Proteomic analysis of plasma from rats following total parenteral nutrition‐induced liver injury

et al. 2015

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Total parenteral nutrition (TPN) is provided as the primary nitrogen source to manage patients with intestinal failure who were not able to sustain themselves on enteral feeds. The most common complication of long-term TPN use is hepatitis. A proteomic approach was used to identify proteins that are differentially expressed in the plasma of rats following TPN-related acute liver injury. Six male rats were randomly assigned to either the saline infusion control group or the TPN infusion group. Our results demonstrate that TPN infusion in rats resulted in hepatic dysfunction and hepatocyte apoptosis. Five proteins that were differentially expressed between TPN infusion and normal rats were determined and validated in vivo. Fascinatingly, the proteomic differential displays, downregulated proteins included peroxiredoxin 2 (PRDX2), alpha-1-antiproteinase (A1AT), and fibrinogen gamma chain (FIBG), which were involved in oxidative stress, inflammatory respondence and cells apoptosis. After TPN infusion, two protein spots showed increased expression, namely, the glucagon receptor (GLR) protein and apolipoprotein A-1 (APOA1), which may mediate the effects of TPN administration on glycogen and lipid metabolism. In this study, proteomic analysis suggested TPN-related acute liver injury could be involved in limiting cellular protection mechanisms against oxidative stress-induced apoptosis. On the basis of the results, we also give molecular evidences replying TPN-related hepatitis.

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Comprehensive genome analysis of hepatitis B virus using nanopore sequencing technology in patients with previously resolved infection and spontaneous reactivation without drug exposure

Yamada,

Uchida,

Kouyama

et al. 2024

Clin J Gastroenterol

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Hepatitis B spliced protein (HBSP) generated by a spliced hepatitis B virus RNA participates in abnormality of fibrin formation and functions by binding to fibrinogen γ chain

Cited by 19 publications

References 21 publications

Interaction of the Hepatitis B Spliced Protein with Cathepsin B Promotes Hepatoma Cell Migration and Invasion

Interaction of the Hepatitis B Spliced Protein with Cathepsin B Promotes Hepatoma Cell Migration and Invasion

Proteomic analysis of plasma from rats following total parenteral nutrition‐induced liver injury

Comprehensive genome analysis of hepatitis B virus using nanopore sequencing technology in patients with previously resolved infection and spontaneous reactivation without drug exposure

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