Cellular Binding of Hepatitis C Virus Envelope Glycoprotein E2 Requires Cell Surface Heparan Sulfate

Barth, Heidi; Schäfer, Christiane; Adah, Mohammed I.; Zhang, Fuming; Linhardt, Robert J.; Toyoda, Hidenao; Kinoshita-Toyoda, Akiko; Toida, Toshihiko; Kuppevelt, Toin H. Van; Depla, Erik; Weizsäcker, Fritz von; Blum, Hubert E.; Baumert, Thomas F.

doi:10.1074/jbc.m302267200

Cited by 420 publications

(385 citation statements)

References 67 publications

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“…The amount of perlecan is very low in normal liver, but increases dramatically in liver fibrosis (Kovalszky et al, 1988). Liver is also a target for a number of pathogens and liver HS has been demonstrated in several cases to play a pivotal role in infectivity (Chen et al, 1997;Rathore et al, 2001;Barth et al, 2003). Liver HSPGs at the endothelial level act as critical receptors for apoE and is involved in lipid metabolism (Bocksch et al, 2001;Dong et al, 2001;Bazin et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Dromedary glycosaminoglycans: Molecular characterization of camel lung and liver heparan sulfate

Warda

Linhardt

2006

Comparative Biochemistry and Physiology Part B: Biochemistry an

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Glycosaminoglycans (GAGs) are the portion of a proteoglycan that determine its final shape and function. The molecular structure of predominant GAG species in camel liver and lung is reported for the first time. The one-humped camel survives in an extreme, arid habitat and, thus, offers a good model to study the role of glycomics on homeostasis. Heparan sulfate (HS) from the lung and liver of the one-humped camel were isolated. Characterization of these newly isolated glycosaminoglycans included 1 H NMR spectroscopy and disaccharide compositional analysis. The relative molecular weight of these GAGs was estimated by gradient polyacrylamide gel electrophoresis and their degree of sulfation was also assessed. Anticoagulant activity was determined using an anti-factor Xa assay and the HS from camel lung shows ~50% of heparin's activity. The structural differences of camel liver GAGs compared to human and porcine liver heparin and HS is discussed. Camel lung heparan sulfate resembles both heparin and HS in its structure and properties suggesting that it is either a highly sulfated form of HS, a mixture of heparin and HS or an undersulfated heparin.

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Section: Introductionmentioning

confidence: 99%

Dromedary glycosaminoglycans: Molecular characterization of camel lung and liver heparan sulfate

Warda

Linhardt

2006

Comparative Biochemistry and Physiology Part B: Biochemistry an

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“…The ability of E2 to bind to CD81 has been widely documented; however, widespread distribution of CD81 on nonpermissive cells (30) led to the view that other liver-specific molecules must also be involved in facilitating entry (19). Several other cell surface molecules have been reported to bind to native HCV particles or recombinant E2, including the low-density lipoprotein receptor (1,51), dendritic-cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and liver/lymph nodespecific intercellular adhesion molecule 3-grabbing integrin (L-SIGN or DC-SIGNR) (20,32,42), glycosaminoglycans (4), and scavenger receptor class B type I (SR-B1) (6,44). Despite early doubts about the function of CD81 in HCV entry, data using recently developed assays of retroviral pseudoparticles (HCVpp) and in vitro infectious clones support a central role for CD81 in mediating infection (6,11,29,31).…”

Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

Identification of Conserved Residues in the E2 Envelope Glycoprotein of the Hepatitis C Virus That Are Critical for CD81 Binding

Owsianka

Timms

Tarr

et al. 2006

J Virol

229

268

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Hepatitis C virus (HCV) cell entry involves interaction between the viral envelope glycoprotein E2 and the cell surface receptor CD81. Knowledge of conserved E2 determinants important for successful binding will facilitate development of entry inhibitors designed to block this interaction. Previous studies have assigned the CD81 binding function to a number of discontinuous regions of E2. To better define specific residues involved in receptor binding, a panel of mutants of HCV envelope proteins was generated, where conserved residues within putative CD81 binding regions were sequentially mutated to alanine. Mutant proteins were tested for binding to a panel of monoclonal antibodies and CD81 and for their ability to form noncovalent heterodimers and confer infectivity in the retroviral pseudoparticle (HCVpp) assay. Detection by conformation-sensitive monoclonal antibodies indicated that the mutant proteins were correctly folded. Mutant proteins fell into three groups: those that bound CD81 and conferred HCVpp infectivity, those that abrogated both CD81 binding and HCVpp infectivity, and a final group containing mutants that were able to bind CD81 but were noninfectious in the HCVpp assay. Specific amino acids conserved across all genotypes that were critical for CD81 binding were W420, Y527, W529, G530, and D535. These data significantly increase our understanding of the CD81 receptor-E2 binding process.Hepatitis C virus (HCV) is the sole member of the Hepacivirus genus within the family Flaviviridae. It is a major cause of community-acquired and posttransfusion hepatitis. More than 170 million people worldwide are seropositive for HCV, and only 20% of those infected are able to clear the virus. In the remaining 80% of individuals, the virus persists and can

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“…Indeed, HCV entry is a multistep process involving the interactions of both viral and cellular components of the LVPs with several host cell receptors. The initial attachment of the virus to the cell is likely mediated by glycosaminoglycans (14), by the LDL receptor (15), and/or by the scavenger receptor BI (SR-BI) (16), which all bind apolipoproteins incorporated on the surface of viral particles. Then, a complex interaction between viral glycoproteins, SR-BI, and other cellular host factors such as the CD81 tetraspanin (17) and the tight junction proteins Claudin-1 (18) and Occludin (19) allows entry and internalization of the viral particles (20).…”

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confidence: 99%

Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles Produced in a Humanized Liver Mouse Model

Calattini¹,

Fusil²,

Mancip³

et al. 2015

Journal of Biological Chemistry

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Background:We compared viral subpopulations derived from humanized liver mouse model versus cell culture. Results:In vivo and in vitro produced particles show different biophysical properties and receptor usage. Conclusion:In vivo models allow functional investigations on how lipid metabolism and hepatic environment influence HCV entry. Significance: HCV produced from humanized liver mice may better reflect the characteristics of virus from HCV-infected patients.

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Cellular Binding of Hepatitis C Virus Envelope Glycoprotein E2 Requires Cell Surface Heparan Sulfate

Cited by 420 publications

References 67 publications

Dromedary glycosaminoglycans: Molecular characterization of camel lung and liver heparan sulfate

Dromedary glycosaminoglycans: Molecular characterization of camel lung and liver heparan sulfate

Identification of Conserved Residues in the E2 Envelope Glycoprotein of the Hepatitis C Virus That Are Critical for CD81 Binding

Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles Produced in a Humanized Liver Mouse Model

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