scholarly journals Mechanism of Structural Tuning of the Hepatitis C Virus Human Cellular Receptor CD81 Large Extracellular Loop

Structure ◽  
2018 ◽  
Vol 26 (1) ◽  
pp. 181 ◽  
Author(s):  
Eva S. Cunha ◽  
Pedro Sfriso ◽  
Adriana L. Rojas ◽  
Pietro Roversi ◽  
Adam Hospital ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cellular Receptor ◽  
Extracellular Loop ◽  
Large Extracellular Loop

scholarly journals Mechanism of Structural Tuning of the Hepatitis C Virus Human Cellular Receptor CD81 Large Extracellular Loop

Structure ◽  
2017 ◽  
Vol 25 (1) ◽  
pp. 53-65 ◽  
Author(s):  
Eva S. Cunha ◽  
Pedro Sfriso ◽  
Adriana L. Rojas ◽  
Pietro Roversi ◽  
Adam Hospital ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cellular Receptor ◽  
Extracellular Loop ◽  
Large Extracellular Loop

scholarly journals Identification of the Hepatitis C Virus E2 Glycoprotein Binding Site on the Large Extracellular Loop of CD81

2002 ◽  
Vol 76 (21) ◽  
pp. 11143-11147 ◽  
Author(s):  
Heidi E. Drummer ◽  
Kirilee A. Wilson ◽  
Pantelis Poumbourios
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Binding Site ◽  
Nk Cell ◽  
Cell Activity ◽  
Random Mutagenesis ◽  
Extracellular Loop ◽  
Human T Cell ◽  
Large Extracellular Loop

ABSTRACT The binding of hepatitis C virus glycoprotein E2 to the large extracellular loop (LEL) of CD81 has been shown to modulate human T-cell and NK cell activity in vitro. Using random mutagenesis of a chimera of maltose-binding protein and LEL residues 113 to 201, we have determined that the E2-binding site on CD81 comprises residues Ile182, Phe186, Asn184, and Leu162. These findings reveal an E2-binding surface of approximately 806 Å2 and potential target sites for the development of small-molecule inhibitors of E2 binding.

scholarly journals CD81 Receptor Regions outside the Large Extracellular Loop Determine Hepatitis C Virus Entry into Hepatoma Cells

Viruses ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 207 ◽  
Author(s):  
Pia Banse ◽  
Rebecca Moeller ◽  
Janina Bruening ◽  
Lisa Lasswitz ◽  
Sina Kahl ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Entry ◽  
Hepatoma Cells ◽  
Extracellular Loop ◽  
Large Extracellular Loop

scholarly journals Diverse CD81 Proteins Support Hepatitis C Virus Infection

2006 ◽  
Vol 80 (22) ◽  
pp. 11331-11342 ◽  
Author(s):  
Mike Flint ◽  
Thomas von Hahn ◽  
Jie Zhang ◽  
Michelle Farquhar ◽  
Christopher T. Jones ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Viral Entry ◽  
Hepatitis C Virus Infection ◽  
Extracellular Loop ◽  
Virus Attachment ◽  
Susceptibility To Infection ◽  
Cell Incubation ◽  
Large Extracellular Loop

ABSTRACT Hepatitis C virus (HCV) entry is dependent on CD81. To investigate whether the CD81 sequence is a determinant of HCV host range, we expressed a panel of diverse CD81 proteins and tested their ability to interact with HCV. CD81 large extracellular loop (LEL) sequences were expressed as recombinant proteins; the human and, to a low level, the African green monkey sequences bound soluble HCV E2 (sE2) and inhibited infection by retrovirus pseudotype particles bearing HCV glycoproteins (HCVpp). In contrast, mouse or rat CD81 proteins failed to bind sE2 or to inhibit HCVpp infection. However, CD81 proteins from all species, when expressed in HepG2 cells, conferred susceptibility to infection by HCVpp and cell culture-grown HCV to various levels, with the rat sequence being the least efficient. Recombinant human CD81 LEL inhibited HCVpp infectivity only if present during the virus-cell incubation, consistent with a role for CD81 after virus attachment. Amino acid changes that abrogate sE2 binding (I182F, N184Y, and F186S, alone or in combination) were introduced into human CD81. All three amino acid changes in human CD81 resulted in a molecule that still supported HCVpp infection, albeit with reduced efficiency. In summary, there is a remarkable plasticity in the range of CD81 sequences that can support HCV entry, suggesting that CD81 polymorphism may contribute to, but alone does not define, the HCV susceptibility of a species. In addition, the capacity to support viral entry is only partially reflected by assays measuring sE2 interaction with recombinant or full-length CD81 proteins.

scholarly journals Interaction of hepatitis C virus envelope glycoprotein E2 with the large extracellular loop of tupaia CD81

2009 ◽  
Vol 15 (2) ◽  
pp. 240 ◽  
Author(s):  
Zhan-Fei Tian ◽  
Hong Shen ◽  
Xi-Hua Fu ◽  
Yi-Chun Chen ◽  
Hubert E Blum ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Envelope Glycoprotein ◽  
Extracellular Loop ◽  
Virus Envelope ◽  
Large Extracellular Loop ◽  
Glycoprotein E2

scholarly journals Polymer Particles Bearing Recombinant LEL CD81 as Trapping Systems for Hepatitis C Virus

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 672
Author(s):  
Dmitry Polyakov ◽  
Ekaterina Sinitsyna ◽  
Natalia Grudinina ◽  
Mariia Antipchik ◽  
Rodion Sakhabeev ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Fusion Protein ◽  
Core Protein ◽  
Chemical Properties ◽  
Extracellular Loop ◽  
E Coli ◽  
Physico Chemical ◽  
Urgent Task ◽  
Large Extracellular Loop

Hepatitis C is one of the most common social diseases in the world. The improvements in both the early diagnostics of the hepatitis C and the treatment of acute viremia caused by hepatitis C virus are undoubtedly an urgent task. In present work, we offered the micro- and nanotraps for the capturing of HCV. As a capturing moiety, we designed and synthesized in E. coli a fusion protein consisting of large extracellular loop of CD81 receptor and streptavidin as spacing part. The obtained protein has been immobilized on the surface of PLA-based micro- and nanoparticles. The developed trapping systems were characterized in terms of their physico-chemical properties. In order to illustrate the ability of developed micro- and nanotraps to bind HCV, E2 core protein of HCV was synthesized as a fusion protein with GFP. Interaction of E2 protein and hepatitis C virus-mimicking particles with the developed trapping systems were testified by several methods.

Definition of the peptide mimotope of cellular receptor for hepatitis C virus E2 protein using random peptide library

2001 ◽  
Vol 1 (1) ◽  
pp. 77
Author(s):  
In-Hee Lee ◽  
Jae-Eun Paik ◽  
Sang-Yong Seol ◽  
Dae-Hyun Seog ◽  
Sae-Gwang Park ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Peptide Library ◽  
Cellular Receptor ◽  
E2 Protein ◽  
Random Peptide Library ◽  
Random Peptide ◽  
Definition Of

scholarly journals Claudin-6 and Claudin-9 Function as Additional Coreceptors for Hepatitis C Virus

2007 ◽  
Vol 81 (22) ◽  
pp. 12465-12471 ◽  
Author(s):  
Aihua Zheng ◽  
Fei Yuan ◽  
Yanqin Li ◽  
Fangfang Zhu ◽  
Pingping Hou ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sequence Comparison ◽  
Mononuclear Cells ◽  
Primary Site ◽  
Target Cells ◽  
Extracellular Loop ◽  
Permissive Cell ◽  
Peripheral Blood Mononuclear ◽  
Global Challenge

ABSTRACT Hepatitis C virus (HCV) is a global challenge to public health. Several factors have been proven to be critical for HCV entry, including the newly identified claudin-1 (CLDN1). However, the mechanism of HCV entry is still obscure. Presently, among the 20 members of the claudin family identified in humans so far, CLDN1 has been the only member shown to be necessary for HCV entry. Recently, we discovered that Bel7402, an HCV-permissive cell line, does not express CLDN1 but expresses other members of claudin family. Among these claudins, CLDN9 was able to mediate HCV entry just as efficiently as CLDN1. We then examined if other members of the claudin family could mediate entry. We show that CLDN6 and CLDN9, but not CLDN2, CLDN3, CLDN4, CLDN7, CLDN11, CLDN12, CLDN15, CLDN17, and CLDN23, were able to mediate the entry of HCV into target cells. We found that CLDN6 and CLDN9 are expressed in the liver, the primary site of HCV replication. We also showed that CLDN6 and CLDN9, but not CLDN1, are expressed in peripheral blood mononuclear cells, an additional site of HCV replication. Through sequence comparison and mutagenesis studies, we show that residues N38 and V45 in the first extracellular loop (EL1) of CLDN9 are necessary for HCV entry.

scholarly journals Optimized cell systems for the investigation of hepatitis C virus E1E2 glycoproteins

2020 ◽  
Author(s):  
Mphatso D. Kalemera ◽  
Joan Capella-Pujol ◽  
Ana Chumbe ◽  
Alexander Underwood ◽  
Rowena A. Bull ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Complex Type ◽  
Functional Studies ◽  
Endogenous Expression ◽  
F Cells ◽  
Large Extracellular Loop ◽  
Made In

Great strides have been made in understanding and treating hepatitis C virus (HCV) thanks to the development of various experimental systems including cell-culture-proficient HCV, the HCV pseudoparticle system and soluble envelope glycoproteins. The HCV pseudoparticle (HCVpp) system is a platform used extensively in studies of cell entry, screening of novel entry inhibitors, assessing the phenotypes of clinically observed E1 and E2 glycoproteins and, most pertinently, in characterizing neutralizing antibody breadth induced upon vaccination and natural infection in patients. Nonetheless, some patient-derived clones produce pseudoparticles that are either non-infectious or exhibit infectivity too low for meaningful phenotyping. The mechanisms governing whether any particular clone produces infectious pseudoparticles are poorly understood. Here we show that endogenous expression of CD81, an HCV receptor and a cognate-binding partner of E2, in producer HEK 293T cells is detrimental to the infectivity of recovered HCVpp for most strains. Many HCVpp clones exhibited increased infectivity or had their infectivity rescued when they were produced in 293T cells CRISPR/Cas9 engineered to ablate CD81 expression (293TCD81KO). Clones made in 293TCD81KO cells were antigenically very similar to their matched counterparts made parental cells and appear to honour the accepted HCV entry pathway. Deletion of CD81 did not appreciably increase the recovered titres of soluble E2 (sE2). However, we did, unexpectedly, find that monomeric sE2 made in 293T cells and Freestyle 293-F (293-F) cells exhibit important differences. We found that 293-F-produced sE2 harbours mostly complex-type glycans whilst 293T-produced sE2 displays a heterogeneous mixture of both complex-type glycans and high-mannose or hybrid-type glycans. Moreover, sE2 produced in 293T cells is antigenically superior; exhibiting increased binding to conformational antibodies and the large extracellular loop of CD81. In summary, this work describes an optimal cell line for the production of HCVpp and reveals that sE2 made in 293T and 293-F cells are not antigenic equals. Our findings have implications for functional studies of E1E2 and the production of candidate immunogens.

Sign in / Sign up

Export Citation Format

Share Document