Specific interaction of the envelope glycoproteins E1 and E2 with liver heparan sulfate involved in the tissue tropismatic infection by hepatitis C virus

Kobayashi, Fumi; Yamada, Shuhei; Taguwa, Shuhei; Kataoka, Chikako; Naito, Satomi; Hama, Yoshiki; Tani, Hideki; Matsuura, Yoshiharu; Sugahara, Kazuyuki

doi:10.1007/s10719-012-9388-z

Cited by 20 publications

(16 citation statements)

References 55 publications

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“…One is through E1 and E2 envelope glycoproteins, which bind to HS and promote HCV attachment and entry (76). E1 and E2 glycoproteins bind more avidly to HS extracted from the liver, consistent with the observations that these glycoproteins bind preferentially to highly sulfated HS, liver HS contains a higher density of sulfate groups compared to HS from other tissues, and that HCV primarily infects hepatocytes (77). A second mechanism is a bridging mechanism where HCV binds to apoliprotein E (apoE) and uses apoE to bind to cell surface HS for their attachment and entry (78).…”

Section: Gag Subversion Mechanisms At Portals Of Entrysupporting

confidence: 83%

“…For example, studies with HP oligosaccharides, modified HP, and gene silencing of HS biosynthetic enzymes showed that N - and 6- O -sulfation, but not 2- O -sulfation, and a minimum of HP decasaccharide are required for HCV cellular infection (79). E1 and E2 envelope glycoproteins also bind in an N - and 6- O -sulfate-dependent manner (77), suggesting that E1 and E2 interactions with HS may predominate in HCV infection in vitro . However, the abundance of lipoproteins and apolipoproteins in the circulation suggest that HCV may efficiently bind to apoE4 and use the ability of apoE4 to be endocytosed by syndecan-1 (80) to enter hepatocytes in vivo .…”

Section: Gag Subversion Mechanisms At Portals Of Entrymentioning

confidence: 99%

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Glycosaminoglycans and infection

2016

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Glycosaminoglycans (GAGs) are complex linear polysaccharides expressed in intracellular compartments, at the cell surface, and in the extracellular environment where they interact with various molecules to regulate many cellular processes implicated in health and disease. Subversion of GAGs is a pathogenic strategy shared by a wide variety of microbial pathogens, including viruses, bacteria, parasites, and fungi. Pathogens use GAGs at virtually every major portals of entry to promote their attachment and invasion of host cells, movement from one cell to another, and to protect themselves from immune attack. Pathogens co-opt fundamental activities of GAGs to accomplish these tasks. This ingenious strategy to subvert essential activities of GAGs likely prevented host organisms from deleting or inactivating these mechanisms during their evolution. The goal of this review is to provide a mechanistic overview of our current understanding of how microbes subvert GAGs at major steps of pathogenesis, using select GAG-pathogen interactions as representative examples.

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Section: Gag Subversion Mechanisms At Portals Of Entrysupporting

confidence: 83%

Section: Gag Subversion Mechanisms At Portals Of Entrymentioning

confidence: 99%

Glycosaminoglycans and infection

2016

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“…Both soluble E2 and the E1E2 heterodimer have been shown to directly bind to CD81 and SR-BI, and a direct interaction between the E1E2 heterodimer and CLDN1 has also recently been described (35,36,(42)(43)(44)(45)(46)(47). Interaction with HSPG has been shown to be facilitated by both E1 and E2 (34,48,49). In addition, virion-associated lipid components (apolipoprotein E, apolipoprotein B, apolipoprotein C-1, and cholesterol) have a role in facilitating and modulating interactions with HSPG, lowdensity lipoprotein receptor (LDLR), SR-BI, and NPC1L1 (37,(50)(51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Hepatitis C Virus Envelope Glycoprotein Vaccine Elicits Antibodies Targeting Multiple Epitopes on the Envelope Glycoproteins Associated with Broad Cross-Neutralization

Wong

Bhat

Hockman

et al. 2014

J Virol

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Although effective hepatitis C virus (HCV) antivirals are on the horizon, a global prophylactic vaccine for HCV remains elusive. The diversity of the virus is a major concern for vaccine development; there are 7 major genotypes of HCV found globally. Therefore, a successful vaccine will need to protect against HCV infection by all genotypes. Despite the diversity, many monoclonal antibodies (MAbs) with broadly cross-neutralizing activity have been described, suggesting the presence of conserved epitopes that can be targeted to prevent infection. Similarly, a vaccine comprising recombinant envelope glycoproteins (rE1E2) derived from the genotype 1a HCV-1 strain has been shown to be capable of eliciting cross-neutralizing antibodies in guinea pigs, chimpanzees, and healthy human volunteers. In order to investigate the basis for this cross-neutralization, epitope mapping of anti-E1E2 antibodies present within antisera from goats and humans immunized with HCV-1 rE1E2 was conducted through peptide mapping and competition studies with a panel of cross-neutralizing MAbs targeting various epitopes within E1E2. The immunized-goat antiserum was shown to compete with the binding of all MAbs tested (AP33, HC33.4, HC84.26, 1:7, AR3B, AR4A, AR5A, IGH526, and A4). Antisera showed the best competition against HC84.26 and AR3B and the weakest competition against AR4A. Furthermore, antisera from five immunized human vaccinees were shown to compete with five preselected MAbs (AP33, AR3B, AR4A, AR5A, and IGH526). These data show that immunization with HCV-1 rE1E2 elicits antibodies targeting multiple cross-neutralizing epitopes. Our results further support the use of such a vaccine antigen to induce cross-genotype neutralization. IMPORTANCEAn effective prophylactic vaccine for HCV is needed for optimal control of the disease burden. The high diversity of HCV has posed a challenge for developing vaccines that elicit neutralizing antibodies for protection against infection. Despite this, we have previously shown that a vaccine comprising recombinant envelope glycoproteins derived from a single genotype 1a strain was capable of eliciting a cross-neutralizing antibody response in human volunteers. Here, we have used competition binding assays and peptide binding assays to show that antibodies present in the antisera from vaccinated goats and humans bind epitopes overlapping with those of a variety of well-characterized cross-neutralizing monoclonal antibodies. This provides a mechanism for the cross-neutralizing human antisera: antibodies present in the antisera bind to conserved regions associated with cross-neutralization. Importantly, this work provides further support for a vaccine comprising recombinant envelope glycoproteins, perhaps in a formulation with a vaccine component eliciting strong anti-HCV CD4 ؉ and CD8 ؉ T cell responses.

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“…The initial cell interactions have been proposed to occur through the association of the virus with apolipoproteins B and especially E (ApoB and ApoE) (13)(14)(15)(16). ApoE has been implicated in virus attachment to the host cell (17) by interaction with heparan sulfate proteoglycans (HSPGs) (18), whereas others have found recombinant E1 and E2 to interact directly with liverderived HSPGs (19). However, a recent study demonstrated that virus-associated ApoE is responsible for interactions mediating attachment between the cell-associated HSPG syndecan 1 and HCV (20).…”

mentioning

confidence: 99%

Hypervariable Region 1 Deletion and Required Adaptive Envelope Mutations Confer Decreased Dependency on Scavenger Receptor Class B Type I and Low-Density Lipoprotein Receptor for Hepatitis C Virus

Prentoe

Serre

Ramírez

et al. 2014

J Virol

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c Hypervariable region 1 (HVR1) of envelope protein 2 (E2) of hepatitis C virus (HCV) serves important yet undefined roles in the viral life cycle. We previously showed that the viability of HVR1-deleted JFH1-based recombinants with Core-NS2 of H77 (H77 ⌬HVR1 , genotype 1a) and S52 (S52 ⌬HVR1 , genotype 3a) in Huh7.5 cells was rescued by E2 substitutions N476D/S733F and an E1 substitution, A369V, respectively; HVR1-deleted J6 (J6 ⌬HVR1 , genotype 2a) was fully viable. In single-cycle production assays, where HCV RNA was transfected into entry-deficient Huh7-derived S29 cells with low CD81 expression, we found no effect of HVR1 deletion on replication or particle release for H77 and S52. HCV pseudoparticle assays in Huh7.5 cells showed that HVR1 deletion decreased entry by 20-to 100-fold for H77, J6, and S52; N476D/S733F restored entry for H77 ⌬HVR1 , while A369V further impaired S52 ⌬HVR1 entry. We investigated receptor usage by antibody blocking and receptor silencing in Huh7.5 cells, followed by inoculation of parental and HVR1-deleted HCV recombinants. Compared to parental viruses, scavenger receptor class B type I (SR-BI) dependency was decreased for H77 ⌬HVR1/N476D/S733F , H77 N476D/S733F , S52 ⌬HVR1/A369V , and S52 A369V , but not for J6 ⌬HVR1 . Low-density lipoprotein receptor (LDLr) dependency was decreased for HVR1-deleted viruses, but not for H77 N476D/S733F and S52 A369V . Soluble LDLr neutralization revealed strong inhibition of parental HCV but limited effect against HVR1-deleted viruses. Apolipoprotein E (ApoE)-specific HCV neutralization was similar for H77, J6, and S52 viruses with and without HVR1. In conclusion, HVR1 and HVR1-related adaptive envelope mutations appeared to be involved in LDLr and SR-BI dependency, respectively. Also, LDLr served ApoE-independent but HVR1-dependent functions in HCV entry.A pproximately 180 million people worldwide are chronically infected with hepatitis C virus (HCV) with an increased risk of developing liver cirrhosis and hepatocellular carcinoma (1). HCV is an enveloped positive-strand RNA virus of the family Flaviviridae with a 9.6-kb genome consisting of 5= and 3= untranslated regions (UTRs) flanking an open reading frame (ORF) that encodes a single polyprotein. This polyprotein is processed into structural proteins (Core and envelope proteins E1 and E2), p7, and six nonstructural proteins (NS2 to NS5B) (2). HCV is a highly diverse virus, and isolates are divided into seven major genotypes, most containing multiple subtypes and differing by ϳ30% and ϳ20%, respectively, at the nucleotide and amino acid levels (2). Previous studies have shown genotype or isolate differences when analyzing HCV neutralization and in reverse genetics studies of HCV proteins (3-5). This highlights the importance of including several isolates, preferably of diverse genotypes, in functional studies.While the process of HCV entry into the human hepatocyte remains incompletely understood, it is known to be a complex multistep process involving several receptors acting at (i) initial a...

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Specific interaction of the envelope glycoproteins E1 and E2 with liver heparan sulfate involved in the tissue tropismatic infection by hepatitis C virus

Cited by 20 publications

References 55 publications

Glycosaminoglycans and infection

Glycosaminoglycans and infection

Recombinant Hepatitis C Virus Envelope Glycoprotein Vaccine Elicits Antibodies Targeting Multiple Epitopes on the Envelope Glycoproteins Associated with Broad Cross-Neutralization

Hypervariable Region 1 Deletion and Required Adaptive Envelope Mutations Confer Decreased Dependency on Scavenger Receptor Class B Type I and Low-Density Lipoprotein Receptor for Hepatitis C Virus

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