scholarly journals Hepatitis C virus entry: potential receptors and their biological functions

2006 ◽  
Vol 87 (5) ◽  
pp. 1075-1084 ◽  
Author(s):  
Laurence Cocquerel ◽  
Cécile Voisset ◽  
Jean Dubuisson
Keyword(s):  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Low Density Lipoprotein ◽  
Heparan Sulphate ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Type I ◽  
Major Step ◽  
Class B

Several cellular molecules have been identified as putative receptors for Hepatitis C virus (HCV): CD81 tetraspanin, scavenger receptor class B type I (SR-BI), mannose-binding lectins DC-SIGN and L-SIGN, low-density lipoprotein receptor, heparan sulphate proteoglycans and the asialoglycoprotein receptor. Due to difficulties in propagating HCV in cell culture, most of these molecules have been identified by analysing their interaction with a soluble, truncated form of HCV glycoprotein E2. A recent major step in investigating HCV entry was the development of pseudoparticles (HCVpp), consisting of unmodified HCV envelope glycoproteins assembled onto retroviral core particles. This system has allowed the investigation of the role of candidate receptors in the early steps of the HCV life cycle and the data obtained can now be confirmed with the help of a newly developed cell-culture system that allows efficient amplification of HCV (HCVcc). Interestingly, CD81 and SR-BI have been shown to play direct roles in HCVpp and/or HCVcc entry. However, co-expression of CD81 and SR-BI in non-hepatic cell lines does not lead to HCVpp entry, indicating that other molecule(s), expressed only in hepatic cells, are necessary for HCV entry. In this review, the molecules that have been proposed as potential HCV receptors are described and the experimental data indicating that CD81 and SR-BI are potentially involved in HCV entry are presented.

O.192 Scavenger receptor class B type I is a co-receptor for infection with cell culture-derived hepatitis C virus

2006 ◽  
Vol 36 ◽  
pp. S58
Author(s):  
M.B. Zeisel ◽  
E.K. Schnober ◽  
A. Haberstroh ◽  
D. Lavillette ◽  
F. Cosset ◽  
...  
Keyword(s):  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Scavenger Receptor ◽  
Type I ◽  
Scavenger Receptor Class ◽  
Class B

scholarly journals Hepatitis C virus entry into the hepatocyte

2011 ◽  
Vol 6 (6) ◽  
pp. 933-945 ◽  
Author(s):  
Sandrine Belouzard ◽  
Laurence Cocquerel ◽  
Jean Dubuisson
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Current Knowledge ◽  
Virus Entry ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Surface Proteins ◽  
Enveloped Virus ◽  
Early Endosomes

AbstractHepatitis C virus (HCV) is a small enveloped virus with a positive stranded RNA genome belonging to the Flaviviridae family. The virion has the unique ability of forming a complex with lipoproteins, which is known as the lipoviroparticle. Lipoprotein components as well as the envelope proteins, E1 and E2, play a key role in virus entry into the hepatocyte. HCV entry is a complex multistep process involving sequential interactions with several cell surface proteins. The virus relies on glycosaminoglycans and possibly the low-density lipoprotein receptors to attach to cells. Furthermore, four specific entry factors are involved in the following steps which lead to virus internalization and fusion in early endosomes. These molecules are the scavenger receptor SRB1, tetraspanin CD81 and two tight junction proteins, Claudin-1 and Occludin. Although they are essential to HCV entry, the precise role of these molecules is not completely understood. Finally, hepatocytes are highly polarized cells and which likely affects the entry process. Our current knowledge on HCV entry is summarized in this review.

Scavenger Receptor Class B Type I Mediates Cell Entry of Hepatitis C Virus

2008 ◽  
Vol 36 (6) ◽  
pp. 1319-1325 ◽  
Author(s):  
ZS Jia ◽  
DW Du ◽  
YF Lei ◽  
X Wei ◽  
W Yin ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cho Cells ◽  
Hepg2 Cells ◽  
Scavenger Receptor ◽  
Chinese Hamster ◽  
Hcv Infection ◽  
Type I ◽  
Scavenger Receptor Class ◽  
Class B

This study assessed the functional role of human scavenger receptor class B type I (SR-BI) as a putative hepatitis C virus (HCV) receptor using Chinese hamster ovary (CHO) cells transfected with human SR-BI (CHO–huSR-BI). The expression of SR-BI by primary Tupaia hepatocytes (PTHs), human hepatocarcinoma cell line (HepG2) cells, untransfected CHO cells and CHO–huSR-BI cells was analysed by Western blotting. Receptor competition assays showed that anti-SR-BI antibodies that block the binding of soluble envelope glycoprotein E2 could prevent HCV infection. Pre-incubation of CHO–huSR-BI and HepG2 cells with anti-SR-BI antibodies resulted in marked inhibition of E2 binding. After incubation with HCV RNA-positive serum from a patient with chronic HCV infection, however, HCV infection could not be detected in CHO–huSR-BI cells, but was detected in PTHs. These results demonstrate that, whilst SR-BI represents an important cell surface molecule for HCV infection, the presence of SR-BI alone is insufficient for HCV entry.

56 Scavenger receptor class B type i mediates uptake and cross-presentation of hepatitis C virus by human dendritic cells

2006 ◽  
Vol 44 ◽  
pp. S26
Author(s):  
H. Barth ◽  
E.K. Schnober ◽  
C. Neumann-Haefelin ◽  
R. Thimme ◽  
H.E. Blum ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Scavenger Receptor ◽  
Type I ◽  
Cross Presentation ◽  
Scavenger Receptor Class ◽  
Class B ◽  
Human Dendritic Cells

scholarly journals Scavenger Receptor Class B Type I Is More Conducive to Hepatitis C Virus Invasion Compared with Low-Density Lipoprotein Receptor

2020 ◽  
Author(s):  
Xiangyi Cao ◽  
Qiong Kang ◽  
Deng Jiang ◽  
Jun Xiao ◽  
Yanyu Zhang ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Type I ◽  
Lipoprotein Receptor ◽  
Scavenger Receptor Class ◽  
Recombinant Cells ◽  
Class B ◽  
Density Lipoprotein Receptor

Abstract Background: Hepatitis C virus is the major cause of chronic hepatitis which may deteriorate into liver cirrhosis or hepatocellular carcinoma. A number of studies have demonstrated that HCV cell entry is a complex multi-step process involving several cellular proteins, such as scavenger receptor class B type I (SR-BI), tetraspanin CD81, tight junction protein claudin-1 (CLDN-1) and occludin (OCLN). The low-density lipoprotein receptor (LDLR) is an important factor during the initial HCV particle-binding step, which interacts with the complex formed between the virus particle and the lipoprotein in the blood. However, the process of HCV early infection is not well-established, with many details remaining to be elucidated.This research aimed to study the early entry stage of HCV virus particles and the role of LDLR more effectively.Methods: Recombinant murine cell models of HCV infection in vitro was constructed, that expressed human HCV receptors, such as LDLR, CD81, SR BI, CLDN-1, and OCLN. These factors were also introduced to mice by hydrodynamic delivery to construct a humanized mouse model of HCV infection in vivo.Expression levels of the mRNA of HCV entry factors in recombinant cells were measured by qRT-PCR.Western blotting was used to determine whether the recombinant cells successfully expressed cellular proteins. HCV RNA was assayed by q-PCR following the incublation of HCVsd and HCVcc with the transgenice.Results: Transgenic murine cell lines and mice were developed successfully, and expressed four or five human HCV entry factors in tandem or individually, respectively. We found that all of these transgenic cells and mice were susceptible to HCV, and five entry factors (5EF) rendered higher infectivity. Additionally, we observed that four entry factors (4EF/hLDLR-) could facilitate abundant HCV entry, but four other factors (4EF/hSR-BI-) were less effective.Conclusions: Whether in vitro or in vivo, SR-BI is an essential factor in HCV invasion, and target cells and mice were more vulnerable to the virus in the presence of SR-BI than LDLR. These results suggested that SR-BI may be a potential drug target to inhibit HCV early infection, and the absence of LDLR could reduce the infectivity to the virus.

scholarly journals Global and local envelope protein dynamics of hepatitis C virus determine broad antibody sensitivity

2020 ◽  
Vol 6 (35) ◽  
pp. eabb5938 ◽  
Author(s):  
Elias H. Augestad ◽  
Matteo Castelli ◽  
Nicola Clementi ◽  
Luisa J. Ströh ◽  
Thomas Krey ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Envelope Protein ◽  
Neutralizing Antibodies ◽  
Scavenger Receptor ◽  
Hypervariable Region ◽  
Antigenic Site ◽  
Conformational Space ◽  
Type I ◽  
Class B

Broad antibody sensitivity differences of hepatitis C virus (HCV) isolates and their ability to persist in the presence of neutralizing antibodies (NAbs) remain poorly understood. Here, we show that polymorphisms within glycoprotein E2, including hypervariable region 1 (HVR1) and antigenic site 412 (AS412), broadly affect NAb sensitivity by shifting global envelope protein conformation dynamics between theoretical “closed,” neutralization-resistant and “open,” neutralization-sensitive states. The conformational space of AS412 was skewed toward β-hairpin–like conformations in closed states, which also depended on HVR1, assigning function to these enigmatic E2 regions. Scavenger receptor class B, type I entry dependency of HCV was associated with NAb resistance and correlated perfectly with decreased virus propensity to interact with HCV co-receptor CD81, indicating that decreased NAb sensitivity resulted in a more complex entry pathway. This link between global E1/E2 states and functionally distinct AS412 conformations has important implications for targeting AS412 in rational HCV vaccine designs.

scholarly journals The postbinding activity of scavenger receptor class B type I mediates initiation of hepatitis C virus infection and viral dissemination

Hepatology ◽  
2012 ◽  
Vol 57 (2) ◽  
pp. 492-504 ◽  
Author(s):  
Muhammad N. Zahid ◽  
Marine Turek ◽  
Fei Xiao ◽  
Viet Loan Dao Thi ◽  
Maryse Guérin ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Scavenger Receptor ◽  
Type I ◽  
Hepatitis C Virus Infection ◽  
Viral Dissemination ◽  
Scavenger Receptor Class ◽  
Class B

scholarly journals Role of Scavenger Receptor Class B Type I in Hepatitis C Virus Entry: Kinetics and Molecular Determinants

2009 ◽  
Vol 84 (1) ◽  
pp. 34-43 ◽  
Author(s):  
Maria Teresa Catanese ◽  
Helenia Ansuini ◽  
Rita Graziani ◽  
Thierry Huby ◽  
Martine Moreau ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Entry ◽  
Scavenger Receptor ◽  
Specific Protein ◽  
Early Event ◽  
Type I ◽  
Direct Role ◽  
Scavenger Receptor Class ◽  
Class B

ABSTRACT Scavenger receptor class B type I (SR-BI) is an essential receptor for hepatitis C virus (HCV) and a cell surface high-density-lipoprotein (HDL) receptor. The mechanism of SR-BI-mediated HCV entry, however, is not clearly understood, and the specific protein determinants required for the recognition of the virus envelope are not known. HCV infection is strictly linked to lipoprotein metabolism, and HCV virions may initially interact with SR-BI through associated lipoproteins before subsequent direct interactions of the viral glycoproteins with SR-BI occur. The kinetics of inhibition of cell culture-derived HCV (HCVcc) infection with an anti-SR-BI monoclonal antibody imply that the recognition of SR-BI by HCV is an early event of the infection process. Swapping and single-substitution mutants between mouse and human SR-BI sequences showed reduced binding to the recombinant soluble E2 (sE2) envelope glycoprotein, thus suggesting that the SR-BI interaction with the HCV envelope is likely to involve species-specific protein elements. Most importantly, SR-BI mutants defective for sE2 binding, although retaining wild-type activity for receptor oligomerization and binding to the physiological ligand HDL, were impaired in their ability to fully restore HCVcc infectivity when transduced into an SR-BI-knocked-down Huh-7.5 cell line. These findings suggest a specific and direct role for the identified residues in binding HCV and mediating virus entry. Moreover, the observation that different regions of SR-BI are involved in HCV and HDL binding supports the hypothesis that new therapeutic strategies aimed at interfering with virus/SR-BI recognition are feasible.

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