ArticlePLoS pathogens2018
Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Neuroimmunome of Hepatitis Patients Associates With Disease Severity.Journal of medical virology · 2025Pooled it
- The role of tacstd-2 level in hepatitis C patients (controlled clinical research).The Libyan journal of medicine · 2019Trial
- GRP78 promotes rabies virus entry through interacting with viral receptors.Journal of virology · 2026Article
- XGB-BIF: An XGBoost-Driven Biomarker Identification Framework for Detecting Cancer Using Human Genomic Data.International journal of molecular sciences · 2025Article
- IFN-β production induced by PRRSV is affected by GP3 quantity control and CLND4 interaction.Veterinary research · 2025Article
- Statistical and machine learning based platform-independent key genes identification for hepatocellular carcinoma.PloS one · 2025Article
- Claudins: from gatekeepers of epithelial integrity to potential targets in hepato-pancreato-biliary cancers.Frontiers in oncology · 2024Review
- Identification of KNOP1 as a prognostic marker in hepatocellular carcinoma.Translational cancer research · 2023Article
- Combined Salivary Proteome Profiling and Machine Learning Analysis Provides Insight into Molecular Signature for Autoimmune Liver Diseases Classification.International journal of molecular sciences · 2023Article
- Hepatitis C Virus Disrupts Annexin 5-Mediated Occludin Integrity through Downregulation of Protein Kinase Cα (PKCα) and PKCη Expression, Thereby Promoting Viral Propagation.Journal of virology · 2023Article
- Matrix metalloproteinase-21 promotes metastasis via increasing the recruitment and M2 polarization of macrophages in HCC.Cancer science · 2023Article
- Tight Junctions, the Key Factor in Virus-Related Disease.Pathogens (Basel, Switzerland) · 2022Review
- TACSTD2 upregulation is an early reaction to lung infection.Scientific reports · 2022Article
- Cellular factors involved in the hepatitis C virus life cycle.World journal of gastroenterology · 2021Review
- Hepatitis D Virus and Hepatocellular Carcinoma.Viruses · 2021Review
- Article
- Molecular Signature and Immune Landscape of HCV-Associated Hepatocellular Carcinoma (HCC): Differences and Similarities with HBV-HCC.Journal of hepatocellular carcinoma · 2021Article
- Inhibition of Cathepsin S Restores TGF-β-induced Epithelial-to-mesenchymal Transition and Tight Junction Turnover in Glioblastoma Cells.Journal of Cancer · 2021Article
- Danger-Sensing/Patten Recognition Receptors and Neuroinflammation in Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Trop2: Jack of All Trades, Master of None.Cancers · 2020Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Entry of hepatitis C virus (HCV) into hepatocytes is a complex process that involves numerous cellular factors, including the scavenger receptor class B type 1 (SR-B1), the tetraspanin CD81, and the tight junction (TJ) proteins claudin-1 (CLDN1) and occludin (OCLN). Despite expression of all known HCV-entry factors, in vitro models based on hepatoma cell lines do not fully reproduce the in vivo susceptibility of liver cells to primary HCV isolates, implying the existence of additional host factors which are critical for HCV entry and/or replication. Likewise, HCV replication is severely impaired within hepatocellular carcinoma (HCC) tissue in vivo, but the mechanisms responsible for this restriction are presently unknown. Here, we identify tumor-associated calcium signal transducer 2 (TACSTD2), one of the most downregulated genes in primary HCC tissue, as a host factor that interacts with CLDN1 and OCLN and regulates their cellular localization. TACSTD2 gene silencing disrupts the typical linear distribution of CLDN1 and OCLN along the cellular membrane in both hepatoma cells and primary human hepatocytes, recapitulating the pattern observed in vivo in primary HCC tissue. Mechanistic studies suggest that TACSTD2 is involved in the phosphorylation of CLDN1 and OCLN, which is required for their proper cellular localization. Silencing of TACSTD2 dramatically inhibits HCV infection with a pan-genotype effect that occurs at the level of viral entry. Our study identifies TACSTD2 as a novel regulator of two major HCV-entry factors, CLDN1 and OCLN, which is strongly downregulated in malignant hepatocytes. These results provide new insights into the complex process of HCV entry into hepatocytes and may assist in the development of more efficient cellular systems for HCV propagation in vitro.
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