HBcAg and HBsAg expression in ductular cells in chronic hepatitis B

Delladetsima, J.; Vafiadis, I.; Tassopoulos, Nicolaos C.; Kyriakou, V.; Apostolakl, A.; Smyrnoff, Tatiana

doi:10.1111/j.1600-0676.1994.tb00050.x

Cited by 18 publications

(5 citation statements)

References 24 publications

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“…These findings support previous observations showing HBV components in ductular cells [33] as well as Dane's particles in bile canaliculi and budding of core particles from hepatocytes into the bile canaliculi [12,29] . By using the DHBV model, it has been previously suggested that liver sinusoidal endothelial cells play a key role in the initial uptake of DHBV into the liver [34] .…”

Section: Discussionsupporting

confidence: 82%

Ultrastructural Evidences of Hepatitis B Infection in Human Liver Biopsies Disclose Complex Assembly and Morphogenesis Pathways for Hepatitis B Virus

Falcón¹,

Menéndez²,

Acosta‐Rivero³

et al. 2008

American J. of Infectious Diseases

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Despite of recent advances on acknowledge of hepatitis B virus (HBV) structure and biology, little is known about the morphogenesis and release of virions. In this study, the ultrastructural analysis of HBV components in liver biopsies from chronically HBV-infected patients disclosed complex assembly and morphogenesis pathways for HBV. HBV core (HBcAg) and surface (HBsAg) antigens were specifically identified in all liver biopsies from HVB-infected patients. HBcAg containing core-like particles 24-28 nm in diameter were observed both in nucleus and cytoplasm of hepatocytes. Dane's-like particles were detected either budding to or into the lumen of ER close to HBsAg containing tubular structures. Besides, Dane's-like particles were detected in different vesicular compartments resembling multivesicular endosomes. Other kind of enveloped HBV-like particles similar to the previously described cobra-shaped and horn-shaped particles were also observed in hepatocytes. Some of these particles were connected to the vesicle membrane through a stalk 20-22 nm in diameter. On the other hand, spherical subviral particles (SVP) were frequently observed in cytoplasmic vesicles. Moreover, a minor proportion of enveloped HBV-like particles budding through the plasma membrane to the extracellular space and bile canaliculi were detected. Interestingly, Dane's-like particles in the bile canaliculi and entering into ductular-like cells were shown. Strikingly, Dane's-like particles close to tubular structures and specific immunolabeling for HBcAg both in cytoplasm and nuclei of stellate-like cells were detected. Remarkably, HVB-like particles appeared entering hepatocytes from large cytoplasmic processes of fibrocytes raising the interesting possibility of a cell to cell passage of HBV through direct transcellular migration.

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Section: Discussionsupporting

confidence: 82%

Ultrastructural Evidences of Hepatitis B Infection in Human Liver Biopsies Disclose Complex Assembly and Morphogenesis Pathways for Hepatitis B Virus

Falcón¹,

Menéndez²,

Acosta‐Rivero³

et al. 2008

American J. of Infectious Diseases

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“…Cholangiocytes have been shown to contain both HBV viral antigens (Delladetsima et al, 1994) and DNA (Blum et al, 1983). Because the nature of the HBV receptor is unknown we were not able to confirm expression in the target cells.…”

Section: Figmentioning

confidence: 84%

Preferential Gene Transfer of Lentiviral Vectors to Liver-Derived Cells, Using a Hepatitis B Peptide Displayed on GP64

Markusic¹,

Kanitz²,

Oude-Elferink³

et al. 2007

Human Gene Therapy

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One of the problems that limit the efficiency of viral gene therapy is the lack of specificity of viral particle binding. The development of techniques to target viral particles to specific cell types is therefore important. Because GP64 can efficiently pseudotype lentiviral vectors, we investigated the possibility of using GP64 for lentiviral vector particle targeting. A peptide derived from the hepatitis B virus (HBV) PreS1 protein, with known affinity for an unidentified receptor expressed on hepatocytes, was inserted at amino acid position 278 of the GP64 protein (PreS1-GP64). The GP64 and PreS1-GP64 proteins were expressed and incorporated into lentiviral particles at comparable levels. Flow cytometry measurements confirmed surface display of the PreS1 peptide. The highest titers of PreS1-GP64-pseudotyped lentiviral vectors were observed on liver-derived cell lines. Gene transfer of PreS1-GP64 lentiviral vectors was inhibited by coincubation with an antibody directed against the PreS1 peptide. These data suggest that the PreS1 peptide is involved in viral attachment to the cell surface. The insertion of targeting peptides into the GP64 envelope protein represents a potential approach for the targeting of lentiviral vectors to specific cell types.

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“…6) , thus the possibility of HBV infection of bile duct cells could be ruled out. It has been suggested that a small number of interstitial cells, especially those in the portal area, can also be infected by HBV [ 55 , 57 ]. To eliminate the interference of interstitial cells, we cultured organoids from ICC tissues and corresponding paratumor tissues, respectively, and then carried out IF staining on the organoids and detected the HBV-DNA level in the organoid culture medium.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus-related intrahepatic cholangiocarcinoma originates from hepatocytes

Song

Lin

et al. 2023

Hepatol Int

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Background Hepatitis B virus (HBV) infection is one of the most common risk factors for intrahepatic cholangiocarcinoma (ICC). However, there is no direct evidence of a causal relationship between HBV infection and ICC. In this study, we attempted to prove that ICC may originate from hepatocytes through a pathological study involving ICC tissue-derived organoids. Method The medical records and tumor tissue samples of 182 patients with ICC after hepatectomy were collected. The medical records of 182 patients with ICC were retrospectively analyzed to explore the prognostic factors. A microarray of 182 cases of ICC tumor tissue and 6 cases of normal liver tissue was made, and HBsAg was stained by immunohistochemistry (IHC) to explore the factors closely related to HBV infection. Fresh ICC tissues and corresponding adjacent tissues were collected to make paraffin sections and organoids. Immunofluorescence (IF) staining of factors including HBsAg, CK19, CK7, Hep-Par1 and Albumin (ALB) was performed on both fresh tissues and organoids. In addition, we collected adjacent nontumor tissues of 6 patients with HBV (+) ICC, from which biliary duct tissue and normal liver tissue were isolated and RNA was extracted respectively for quantitative PCR assay. In addition, the expression of HBV-DNA in organoid culture medium was detected by quantitative PCR and PCR electrophoresis. Results A total of 74 of 182 ICC patients were HBsAg positive (40.66%, 74/182). The disease-free survival (DFS) rate of HBsAg (+) ICC patients was significantly lower than that of HBsAg (−) ICC patients (p = 0.0137). IF and IHC showed that HBsAg staining was only visible in HBV (+) ICC fresh tissues and organoids, HBsAg expression was negative in bile duct cells in the portal area. Quantitative PCR assay has shown that the expression of HBs antigen and HBx in normal hepatocytes were significantly higher than that in bile duct epithelial cells. Combined with the IF and IHC staining, it was confirmed that HBV does not infect normal bile duct epithelial cells. In addition, IF also showed that the staining of bile duct markers CK19 and CK7 were only visible in ICC fresh tissue and organoids, and the staining of hepatocyte markers Hep-Par1 and ALB was only visible in normal liver tissue fresh tissue. Real-time PCR and WB had the same results. High levels of HBV-DNA were detected in the culture medium of HBV (+) organoids but not in the culture medium of HBV (−) organoids. Conclusion HBV-related ICC might be derived from hepatocytes. HBV (+) ICC patients had shorter DFS than HBV (−) ICC patients.

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HBcAg and HBsAg expression in ductular cells in chronic hepatitis B

Cited by 18 publications

References 24 publications

Ultrastructural Evidences of Hepatitis B Infection in Human Liver Biopsies Disclose Complex Assembly and Morphogenesis Pathways for Hepatitis B Virus

Ultrastructural Evidences of Hepatitis B Infection in Human Liver Biopsies Disclose Complex Assembly and Morphogenesis Pathways for Hepatitis B Virus

Preferential Gene Transfer of Lentiviral Vectors to Liver-Derived Cells, Using a Hepatitis B Peptide Displayed on GP64

Hepatitis B virus-related intrahepatic cholangiocarcinoma originates from hepatocytes

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