scholarly journals Tight Junction Proteins Claudin-1 and Occludin Control Hepatitis C Virus Entry and Are Downregulated during Infection To Prevent Superinfection

2008 ◽  
Vol 83 (4) ◽  
pp. 2011-2014 ◽  
Author(s):  
Shufeng Liu ◽  
Wei Yang ◽  
Le Shen ◽  
Jerrold R. Turner ◽  
Carolyn B. Coyne ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Tight Junction ◽  
Viral Entry ◽  
Virus Entry ◽  
Tight Junction Proteins ◽  
Functional Changes ◽  
Key Factor ◽  
Junction Proteins ◽  
Mutational Study

ABSTRACT A tight junction (TJ) protein, claudin-1 (CLDN1), was identified recently as a key factor for hepatitis C virus (HCV) entry. Here, we show that another TJ protein, occludin, is also required for HCV entry. Mutational study of CLDN1 revealed that its tight junctional distribution plays an important role in mediating viral entry. Together, these data support the model in which HCV enters liver cells from the TJ. Interestingly, HCV infection of Huh-7 hepatoma cells downregulated the expression of CLDN1 and occludin, preventing superinfection. The altered TJ protein expression may contribute to the morphological and functional changes observed in HCV-infected hepatocytes.

scholarly journals The Tight Junction Proteins Claudin-1, -6, and -9 Are Entry Cofactors for Hepatitis C Virus

2008 ◽  
Vol 82 (7) ◽  
pp. 3555-3560 ◽  
Author(s):  
Laurent Meertens ◽  
Claire Bertaux ◽  
Lisa Cukierman ◽  
Emmanuel Cormier ◽  
Dimitri Lavillette ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Tight Junction ◽  
Tight Junction Proteins ◽  
Junction Protein ◽  
Cellular Factors ◽  
Cd81 Tetraspanin ◽  
Junction Proteins

ABSTRACT Hepatitis C virus (HCV) is a major cause of liver disease in humans. The CD81 tetraspanin is necessary but not sufficient for HCV penetration into hepatocytes, and it was recently reported that the tight junction protein claudin-1 is a critical HCV entry cofactor. Here, we confirm the role of claudin-1 in HCV entry. In addition, we show that claudin-6 and claudin-9 expressed in CD81+ cells also enable the entry of HCV pseudoparticles derived from six of the major genotypes. Whereas claudin-1, -6, and -9 function equally well as entry cofactors in endothelial cells, claudin-1 is more efficient in hepatoma cells. This suggests that additional cellular factors modulate the ability of claudins to function as HCV entry cofactors. Our work has generated novel and essential means to investigate the mechanism of HCV penetration into hepatocytes and the role of the claudin protein family in HCV dissemination, replication, and pathogenesis.

scholarly journals Role of Tricellular Tight Junction Protein Lipolysis-Stimulated Lipoprotein Receptor (LSR) in Cancer Cells

2019 ◽  
Vol 20 (14) ◽  
pp. 3555 ◽  
Author(s):  
Takayuki Kohno ◽  
Takumi Konno ◽  
Takashi Kojima
Keyword(s):  
Tight Junction ◽  
Cancer Progression ◽  
Epithelial Barrier ◽  
Dependent Manner ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Endometrial Cells ◽  
Functional Changes ◽  
Junction Protein ◽  
Junction Proteins

Maintaining a robust epithelial barrier requires the accumulation of tight junction proteins, LSR/angulin-1 and tricellulin, at the tricellular contacts. Alterations in the localization of these proteins temporarily cause epithelial barrier dysfunction, which is closely associated with not only physiological differentiation but also cancer progression and metastasis. In normal human endometrial tissues, the endometrial cells undergo repeated proliferation and differentiation under physiological conditions. Recent observations have revealed that the localization and expression of LSR/angulin-1 and tricellulin are altered in a menstrual cycle-dependent manner. Moreover, it has been shown that endometrial cancer progression affects these alterations. This review highlights the differences in the localization and expression of tight junction proteins in normal endometrial cells and endometrial cancers and how they cause functional changes in cells.

scholarly journals Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process

2020 ◽  
Vol 21 (6) ◽  
pp. 2091 ◽  
Author(s):  
Che Colpitts ◽  
Pei-Ling Tsai ◽  
Mirjam Zeisel
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Entry ◽  
Chronic Infection ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Virus Entry ◽  
Host Factors ◽  
Entry Inhibitors

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and liver disease worldwide. Its tissue and species tropism are largely defined by the viral entry process that is required for subsequent productive viral infection and establishment of chronic infection. This review provides an overview of the viral and host factors involved in HCV entry into hepatocytes, summarizes our understanding of the molecular mechanisms governing this process and highlights the therapeutic potential of host-targeting entry inhibitors.

scholarly journals IFITM1 is a tight junction protein that inhibits hepatitis C virus entry

Hepatology ◽  
2012 ◽  
Vol 57 (2) ◽  
pp. 461-469 ◽  
Author(s):  
Courtney Wilkins ◽  
Jessica Woodward ◽  
Daryl T.-Y. Lau ◽  
Amy Barnes ◽  
Michael Joyce ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Tight Junction ◽  
Virus Entry ◽  
Tight Junction Protein ◽  
Junction Protein

scholarly journals Closing the gap: The tight junction protein occludin and hepatitis C virus entry

Hepatology ◽  
2009 ◽  
Vol 49 (5) ◽  
pp. 1770-1772 ◽  
Author(s):  
Nicholas S. Eyre ◽  
Thomas F. Baumert ◽  
Michael R. Beard
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Tight Junction ◽  
Virus Entry ◽  
Tight Junction Protein ◽  
Junction Protein ◽  
Closing The Gap

Distinct roles in folding, CD81 receptor binding and viral entry for conserved histidine residues of hepatitis C virus glycoprotein E1 and E2

2012 ◽  
Vol 443 (1) ◽  
pp. 85-94 ◽  
Author(s):  
Irene Boo ◽  
Kevin teWierik ◽  
Florian Douam ◽  
Dimitri Lavillette ◽  
Pantelis Poumbourios ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Membrane Fusion ◽  
Receptor Binding ◽  
Viral Entry ◽  
Virus Entry ◽  
Ph Sensitive ◽  
Viral Fusion ◽  
Histidine Residues ◽  
Virus Glycoprotein

The protonation of histidine in acidic environments underpins its role in regulating the function of pH-sensitive proteins. For pH-sensitive viral fusion proteins, histidine protonation in the endosome leads to the activation of their membrane fusion function. The HCV (hepatitis C virus) glycoprotein E1–E2 heterodimer mediates membrane fusion within the endosome, but the roles of conserved histidine residues in the formation of a functional heterodimer and in sensing pH changes is unknown. We examined the functional roles of conserved histidine residues located within E1 and E2. The E1 mutations, H222A/R, H298R and H352A, disrupted E1–E2 heterodimerization and reduced virus entry. A total of five out of six histidine residues located within the E2 RBD (receptor-binding domain) were important for the E2 fold, and their substitution with arginine or alanine caused aberrant heterodimerization and/or CD81 binding. Distinct roles in E1–E2 heterodimerization and in virus entry were identified for His691 and His693 respectively within the membrane-proximal stem region. Viral entry and cell–cell fusion at neutral and low pH values were enhanced with H445R, indicating that the protonation state of His445 is a key regulator of HCV fusion. However, H445R did not overcome the block to virus entry induced by bafilomycin A1, indicating a requirement for an endosomal activation trigger in addition to acidic pH.

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