|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 43, 41624-41630, October 24, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Cell Entry of Hepatitis C Virus Requires a Set of Co-receptors That Include the CD81 Tetraspanin and the SR-B1 Scavenger Receptor*
¶||||
From the
Laboratoire de Vectorologie Rétrovirale et Thérapie Génique, INSERM U412, Institut Fédératif de Recherche 128, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France, the ||Instituto di Recerche di Biologia Molecolare P. Angeletti, 00040 Pomezia, Roma, Italy, and the **CNRS-UPR2511, Institut de Biologie de Lille, Institut Pasteur de Lille, 1 rue Calmette, B. P. 447, 59021 Lille Cedex, France
Received for publication, May 20, 2003 , and in revised form, July 8, 2003.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONEXPERIMENTAL PROCEDURESRESULTSDISCUSSIONREFERENCES |
|---|
Several cell surface molecules have been proposed as receptor candidates, mediating cell entry of hepatitis C virus (HCV) on the basis of their physical association with virions or with soluble HCV E2 glycoproteins. However, due to the lack of infectious HCV particles, evidence that these receptor candidates support infection was missing. Using our recently described infectious HCV pseudotype particles (HCVpp) that display functional E1E2 glycoprotein complexes, here we show that HCV is a pH-dependent virus, implying that its receptor component(s) mediate virion internalization by endocytosis. Expression of the CD81 tetraspanin in non-permissive CD81-negative hepato-carcinoma cells was sufficient to restore susceptibility to HCVpp infection, confirming its critical role as a cell attachment factor. As a cell surface molecule likely to mediate endosomal trafficking, we demonstrate that the human scavenger receptor class B type 1 (SR-B1), a high-density lipoprotein-internalization molecule that we previously proposed as a novel HCV receptor candidate due to its affinity with E2 glycoproteins, is required for infection of CD81-expressing hepatic cells. By receptor competition assays, we found that SR-B1 antibodies that blocked binding of soluble E2 could prevent HCVpp infectivity. Furthermore, we establish that the hyper-variable region 1 of the HCV E2 glycoprotein is a critical determinant mediating entry in SR-B1-positive cells. Finally, by correlating expression of HCV receptors and infectivity, we suggest that, besides CD81 and SR-B1, additional hepatocyte-specific co-factor(s) are necessary for HCV entry.
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONEXPERIMENTAL PROCEDURESRESULTSDISCUSSIONREFERENCES |
|---|
Hepatitis C virus (HCV)1 is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide (1). About 170 million individuals are infected with HCV. The predominant site of replication and probably infection is the liver, yet several studies have suggested that HCV may infect other cell types, such as B cells, monocytes/macrophages, and dendritic cells (2, 3) where it could induce immune dysfunctions. Understanding the molecular basis by which HCV targets liver cells and extra-hepatic sites is critical to unravel the mechanisms of its pathogenesis and disease chronicity. Although substantial progresses have been made on the molecular knowledge of HCV proteins and genomic replication, there is still no efficient and reliable cell culture system available to amplify this virus (4). This represents a major hurdle for the characterization of some steps of HCV lifecycle, such as viral assembly and cell entry. Several surrogate models of HCV virions have been developed to facilitate the study of the steps of cell entry. Production of HCV virus-like particles in insect cells has already been reported (5–8). Yet, although useful to analyze interactions with the cell surface, these particles were not infectious and did not permit functional investigation of the putative HCV receptors. Alternatively, generation of viral pseudotypes is one of the most widely used methods for assaying functional receptors, allowing attachment, penetration, and uncoating to be studied. Thus, pseudotyped vesicular stomatitis virus (VSV) particles have been engineered with chimeric E1 and/or E2 HCV glycoproteins whose transmembrane domains were modified to allow transport to and assembly at the cell surface (9–13). However, as such modifications disturb conformation and functions of the E1E2 complexes (12), their use as a tool to investigate HCV assembly and cell entry remains controversial (9).
Recently, we have successfully generated infectious HCV pseudotype particles that were assembled by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles (14). The presence of a marker gene packaged within these HCV pseudotype particles (HCVpp) allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Our current knowledge of these particles indicates that they mimic the early infection steps of parental HCV as they exhibit a preferential tropism for hepatic cells and as they are specifically neutralized by anti-E2 monoclonal antibodies as well as sera of HCV-infected patients. Our results indicate that the E1 and E2 HCV glycoproteins represent the envelope glycoproteins of wild-type HCV and are both required for infection (14). The infectivity of E1E2-pseudotyped retroviruses for similar cells was confirmed by others, as was the ability of monoclonal antibodies to neutralize the viral particles (15, 16). These pseudotype particles may therefore allow for the first time to decipher the mechanisms of HCV entry into cells.
We recently identified the human scavenger receptor class B type 1 (SR-B1), a high-density lipoprotein-binding molecule, as a putative HCV receptor because of its affinity to soluble E2 glycoproteins (17). Here, we used HCVpp to determine the role of SR-B1 in HCV entry. We show that SR-B1 is required for infection of cells that also express the CD81 tetraspanin and the density lipoprotein receptor (LDLr), two other previously proposed HCV receptor candidates (18, 19). Furthermore, we establish that the hyper-variable region 1 of the HCV E2 glycoprotein is a critical determinant mediating entry in SR-B1-positive cells. Finally, our data indicate that, in addition to LDLr, CD81, and SR-B1, liver-specific co-factor(s) are necessary for HCV entry.
|
EXPERIMENTAL PROCEDURES |
|---|
|
TOPABSTRACTINTRODUCTIONEXPERIMENTAL PROCEDURESRESULTSDISCUSSIONREFERENCES |
|---|
Expression Constructs and Production of HCV Pseudotype Particles—Expression vectors for E1E2 glycoproteins of 1a and 1b genotypes have been described previously (14). They were used to construct by PCR-mediated and oligonucleotide site-directed mutagenesis (details and sequences available upon request) the expression vectors for the mutant E2 glycoproteins that harbor the deletion of the hyper-variable region 1 (del384–410) and/or the V514M and L615H point mutations. The CMV-Gag-Pol murine leukemia virus (MLV) packaging construct, encoding the MLV gag and pol genes, and the MLV-GFP plasmid, encoding an MLV-based transfer vector containing the GFP marker gene, have been described previously (20). The phCMV-G, phCMV-4070A, phCMV-HA, and phCMV-RD (21) expression vectors encode the VSV G protein, the amphotropic MLV glycoprotein, the fowl plague virus hemagglutinin, and the feline endogenous virus RD114 glycoprotein, respectively.
Production of HCV pseudotype particles was carried out as described previously (14). Briefly, 293T cells were transfected with expression vectors encoding the viral components, i.e. E1E2 glycoproteins, retroviral core proteins, and packaging-competent GFP-containing retroviral transfer vectors, using a calcium-phosphate transfection protocol (Clontech, Le Pont de Claix, France). Supernatants containing the pseudotype particles were harvested 24 h later, filtered through 0.45-µm pore-sized membranes, and used in infection assays.
Cells and Infection Assays—Huh-7 human hepatocellular carcinoma (22), PLC/PRF/5 human hepatoma (CRL-8024), Hep3B human hepatocellular carcinoma (HB-8064), HepG2 human hepatocellular carcinoma (HB-8065), 293 human embryo kidney cells (ATCC CRL-1573), HOS human osteosarcoma (CRL-1543), TE671 human rhabdomyosarcoma (CRL-8805), Molt-4 human lymphoblastic leukemia (CRL-1582), HeLa human cervix adenocarcinoma (CCL-2), SW-13 human adreno-cortical carcinoma (CCL-105), and CHO Chinese hamster ovary (CCL-61) were grown as recommended by the ATCC (American Type Culture Collection, Rockville, MD). 293-SR-B1 cells were derived from 293 cells by transfection with pcDNA3-SRB1, an expression vector encoding SR-B1 (or CLA-1), the human scavenger receptor class B type 1 (GenBankTM accession number Z22555 [GenBank] ) (23). CHO-SR-B1 cells were described previously (17). CHO-CD81/SR-B1 and HepG2-CD81 cells were obtained by infection of CHO-SR-B1 and HepG2 cells, respectively, with a retroviral vector containing the human CD81 gene (GenBankTM accession number NM_004356 [GenBank] ). Construct details are available upon request.
Infection assays were performed as described previously (14). Unless otherwise indicated, dilutions of viral supernatants containing the pseudotype particles were added to the cells seeded the day before and plates were incubated for 3 h. The supernatants were then removed and the cells incubated in regular medium for 72 h at 37 °C. The infectious titers, expressed as transducing units (TU)/ml, were deduced from the transduction efficiencies, determined as the percentage of GFP-positive cells measured by FACS analysis (21).
Antibodies—E1 and E2 glycoproteins were detected with the A4 (24) and H52 (25) monoclonal antibodies, respectively. HCVpp core proteins were detected with an anti-capsid (MLV CA) antiserum (ViroMed Biosafety Laboratories). These reagents were used in Western blot analysis of purified pseudotype particles as previously described (14).
JS-81 (BD Biosciences) is a monoclonal antibody reactive with CD81. 15C8 (Oncogene-Science, France) is a monoclonal antibody reactive with the human LDL receptor. The mouse SR-B1 polyclonal serum was raised by muscle genetic immunization of BALB/c mice, using plasmid pVJ-hSR-B1 harboring the full-length human SR-B1 cDNA. Immunization protocol and plasmid vector have been previously described (26). The preimmune sera were collected from the same mice bleeded before immunization. The rat monoclonal antibody 9/27 recognizes an epitope contained in the hypervariable region of the E2 protein of genotype 1a (6).
Cell Binding Assays of E2 Glycoproteins—E2 soluble proteins harboring a C-terminal histidine tag were produced in the supernatants of 293 cells, as previously described (27). Binding of E2 to the cell surface was analyzed using a FACS-based assay. Cells were washed twice in phosphate-buffered saline, 0.2% bovine serum albumin, 10 mM Hepes (FACS buffer). Then, 4 x 105 cells were allowed to bind E2 concentrated supernatants at room temperature for 1 h. After one washing, a biotinylated anti-penta-His mouse monoclonal antibody (Qiagen) was added at a concentration of 2 µg/ml for 30 min at room temperature. Cells were washed again, and cell-bound antibodies were revealed by Streptavidin-R-phycoerythrin conjugated antibodies (Qiagen). For inhibition of binding, cells were pre-incubated with anti-SR-B1 serum, 30 min at 4 °C, as described previously (27).
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONEXPERIMENTAL PROCEDURESRESULTSDISCUSSIONREFERENCES |
|---|
Cell Entry of HCVpp Is pH-dependent—Enveloped viruses penetrate the host cells by a process of fusion between the viral and cell membranes that is catalyzed by a fusogenic activity harbored by viral surface glycoproteins. Activation of such fusion properties occurs in an acid pH-dependent manner, via acidified endosomal vesicles into which the virions are routed following receptor binding (28), or, alternatively, in a pH-independent manner via direct interaction of the viral glycoproteins with their receptors. These two cell entry pathways can be distinguished by assessing the effect in infection assays of drugs that inhibit endosomal-pH acidification, such as weak bases (e.g. chloroquine), and vacuolar H(+)-ATPase inhibitors (e.g. bafilomycin A1) (28). We determined whether entry of HCVpp in Huh-7 hepato-carcinoma cells is likely to proceed via internalization by treating target cells before and during infection with bafilomycin A1. Infectivity of control pseudotype particles generated with pH-independent glycoproteins from MLV-A or RD114 was not affected by bafilomycin A1, at concentrations of up to 50 nM (Fig. 1), consistent with the pH-independent entry route adopted by these retroviruses (29). That bafilomycin A1 seemingly reduced the infectivity of these two control viruses at 100 nM could be clearly attributed to cell toxicity of the drug (data not shown). In contrast, bafilomycin A1 reduced in a dose-dependent manner the infectious titers of HCVpp, as well as the infectivity of pseudotype particles generated with pH-dependent glycoproteins from fowl-plague virus, an avian influenza virus, or from VSV. At 100 nM of bafilomycin A1, the titers of the HCVpp and the pseudotype particles coated with FPV hemagglutinin were reduced by a factor of 30–50-fold (Fig. 1). Similar results were obtained with chloroquine and when using Hep3B as alternative target cells (data not shown). These data indicated that the fusion-activation of HCV E1E2 glycoproteins is pH-dependent and that cell entry of HCVpp most likely occurs by endocytosis. Thus some of the receptors used by HCV to infect the target cells may be responsible for virion internalization.
|
CD81 and SR-B1 Co-expression Is Not Sufficient for HCVpp Cell Entry—The LDLr, the CD81 tetraspanin, and the SR-B1 have been proposed as putative HCV receptors mediating entry into hepatic cells (17–19, 30) on the basis of their physical association with virions or with soluble E2 glycoproteins. Although virion association to LDLr is most likely due to indirect interaction, via virion-bound apolipoproteins (31), direct interaction between soluble E2 and CD81 or SR-B1 could be demonstrated (17, 27). However, due to the lack of infectious HCV particles, evidence that these receptor candidates could support infection was missing. By receptor competition assays, we recently provided evidence that CD81 was involved in the early steps of infection, but was not sufficient to permit infection (14). Indeed, non-hepatic human cells that express CD81 were found to be not or very poorly permissive to infection (Table I), with infectious titers of HCVpp more than 100-fold lower than those measured on Huh-7 cells. Furthermore, ectopic expression of human CD81 in non-permissive murine cells did not restore infection (14). Thus, hepato-carcinoma cells, which coexpress LDLr, CD81, and SR-B1, exhibited the maximal levels of infectivity. Therefore, because SR-B1 is expressed in most cells types, though at highly variable levels (Table I), non-permissiveness to infection may be due to lack of sufficient levels of SR-B1 expression, or, alternatively, to lack of a critical hepatocyte factor(s). To address either of these possibilities, we performed infection assays in CHO cells and 293 human embryo kidney cells that expressed no and low levels of SR-B1, respectively (Table I). CHO cells, which are not permissive to HCVpp infection (14), were engineered to allow stable and constitutive expression of CD81 alone, SR-B1 alone, or both molecules. Expression of either molecule was sufficient to allow binding of E2 soluble glycoproteins (17, 27). All these CHO-derived cells were highly permissive to infection with control pseudotype particles generated with the VSV-G glycoprotein, which binds a non-related receptor. However, despite densities of CD81 and/or SR-B1 molecules similar if not higher than that of the highly permissive Huh-7 cells (Table I), we found no evidence for infection with HCVpp based on genotype 1a (H77 strain) and 1b (J strain) (Fig. 2). In contrast, over-expression of SR-B1 in the poorly permissive 293 cells (14), which naturally express abundant levels of CD81 but very low levels of SR-B1 (Table I), resulted in increased levels of infection for both HCVpp-1a and -1b. Using HCVpp harboring a lacZ marker gene that allows the precise determination of low levels of infectivity in contrast to the GFP marker gene, over 10-fold increased infectivity were detected in 293-SR-B1 cells; yet the infectious titers remained below 103 TU/ml (Table I). Furthermore, we found that several human cells of non-hepatic origin, e.g. HeLa and SW13, expressed LDLr, CD81, and SR-B1 at levels comparable with those detected in hepato-carcinoma cells but were poorly permissive to infection, with infectious titers of HCVpp lower than 103 TU/ml (Table I). Altogether these results indicate that although hCD81 and/or SR-B1 bind HCV E2 glycoproteins and might play a role in cell surface attachment and internalization of HCV, their co-expression in a non-hepatic cell background is not sufficient to support efficient HCVpp infection. Additional interactions between the virions and hepatic cell surface components are likely necessary to allow HCVpp cell entry.
|
|
Both SR-B1 and CD81 Are Necessary for HCVpp Entry into Hepatic Cells—Our previous results established that the highest levels of infectivity were detected in all hepato-carcinoma cells tested, with the notable exception of HepG2 cells (14). Yet, as shown by us, HepG2 cells are fully competent for binding E2 glycoproteins of genotypes 1a and 1b, via interaction with SR-B1 (17). Because these SR-B1-positive cells do not express CD81 (Table I), it remained possible that their poor permissivity to HCVpp was a result of this defect. Interestingly, infection assays performed in HepG2-CD81 cells revealed that expression of CD81 was sufficient to restore HCVpp entry in HepG2 cells by factors of 100- and 30-fold for HCVpp of genotype 1a and 1b, respectively (Fig. 2). Altogether, these results pointed out the involvement of several cell surface molecules in HCV entry in cells of hepatic origin, among which CD81 and SR-B1 seem important, at least to bind E2 glycoproteins.
Thus to specifically investigate a functional role played by SR-B1 in mediating HCVpp cell entry, we designed receptor competition assays using polyclonal antibodies reactive with the SR-B1 ectodomain (Table I). Pre-incubation of target cells with an SR-B1 anti-serum, which blocked binding of soluble E2 glycoproteins from the 1a and 1b HCV strains (Fig. 3A), diminished the infectivity of HCVpp of both genotypes 1a and 1b in Huh-7 (Fig. 3B) and HepG2-CD81 (data not shown) target cells, in a dose-dependent manner. Particularly, at a 1:10 serum dilution, an 80% inhibition of infection on Huh-7 could be obtained for HCVpp based on genotype 1a in a manner correlated with inhibition of soluble E2 binding. No reduction of infectivity was found for control pseudotype particles generated with a non-relevant glycoprotein, derived from RD114 cat endogenous virus (Fig. 3B), demonstrating the specificity of inhibition mediated by the SR-B1 antibodies. Likewise, pre-incubation of target cells with a preimmune serum or with non-relevant monoclonal antibodies inhibited neither binding of recombinant E2 (Fig. 3A) nor HCVpp infection (data not shown). Altogether, these results established that SR-B1 is involved in cell entry of HCVpp, perhaps by being part of an HCV receptor complex with CD81 and/or LDLr.
|
Hyper-variable Region 1 (HVR1) Is Involved in SR-B1-mediated HCVpp Cell Entry—Studies of epitopes that neutralize E2-binding to CD81 have raised the possibility that the CD81-binding domain consists of three discrete segments at both ends of E2 that may join together in the head-to-tail model of E2 glycoprotein homodimer (32). In this putative structure, the CD81-binding domain may be located in close proximity to HVR1, a 27-amino acid long segment found at the amino-terminal end of E2 that has been proposed to play a role in cell attachment (33). Interestingly, in studies with recombinant soluble E2, we found that deletion of HVR1 increased binding to CD81 (27) but decreased binding to SR-B1 (17). Furthermore, this latter phenotype was partially compensated by either the V514M or L615H compensatory mutations (17), which have been selected in the E2 glycoproteins of a HVR1-deleted HCV of genotype 1a following inoculation in chimpanzees (34). These previous results suggested that HVR1 represents an important determinant of SR-B1 binding and that the CD81-binding domain and HVR1 may compete for binding to these two HCV receptors. Thus to investigate the contribution of HVR1 and/or compensatory mutations in cell entry, we generated HCVpp with E1E2 glycoproteins harboring the deletion of HVR1 and/or the V514M and L615H mutations. As demonstrated by Western blot analysis of purified HCVpp (Fig. 4A), these pseudotype particles incorporated normal levels of mutated E1E2, compared with unmodified E1E2 glycoproteins. This indicated that the mutations harbored by the E2 glycoprotein did not impair its folding, maturation, and viral assembly, consistent with studies using soluble recombinant proteins (17). The HVCpp harboring the deletion of HVR1 were infectious (Fig. 4B); yet, compared with parental pseudotype particles, their infectivity was reduced by about 40-fold, on average, for both genotypes. Unexpectedly, the V514M and L615H mutations, introduced alone or together in the E2–1a glycoprotein, resulted in an even more dramatic loss of infectivity of the pseudotype particles harboring HVR1-deleted E2 glycoproteins (Fig. 4B), in contrast to their capacity to compensate an SR-B1-binding defect (17).
|
To further investigate the potential role of HVR1 in cell entry mediated by SR-B1, we performed competition assays of HVR1/SR-B1 interaction with HVR1 or with SR-B1 antibodies. The 9/27 monoclonal antibody, which binds the C-terminal part of the H77 HVR1 sequence (35) and specifically blocks binding of soluble genotype 1a E2 to SR-B1 (17), was found to efficiently neutralize infectivity of HCVpp of genotype 1a but not 1b in a dose-dependent manner (Fig. 4C). Furthermore, no significant neutralization of HVR1-deleted HVCpp-1a by the 9/27 antibody could be detected (Fig. 4C), indicating that neutralization of the parental pseudotype particles by these antibodies occurs via blocking of HVR1. In agreement with these findings, the SR-B1 antibodies were unable to inhibit the HVR1-deleted HCVpp, most likely because SR-B1-binding of the latter viruses was abolished, in contrast to pseudotype particles generated with unmodified E1E2 glycoproteins (Fig. 4D).
Altogether these results are consistent with a role for HVR1 in HCVpp entry via SR-B1. That the HVR1-deleted HCVpp were still infectious, albeit at significantly reduced levels, may be due to residual binding to SR-B1 or, alternatively, to increased binding to CD81.
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONEXPERIMENTAL PROCEDURESRESULTSDISCUSSIONREFERENCES |
|---|
Enveloped viruses enter into cells via a series of steps that involve, on the one hand, interactions between the viral surface glycoproteins and several cell surface molecules, called receptors and co-receptors, and, on the other hand, activation of cell entry pathways that lead to internalization of the viral particles. In the absence of a suitable cell culture system for HCV, an alternative approach to search for candidate receptors has been to use truncated soluble forms of HCV glycoproteins for binding studies to human cells. By using a soluble form of E2 as a probe, CD81 has been identified as a putative receptor for HCV (19). With a very similar approach, the SR-B1 scavenger receptor (17) and the mannose-binding lectins, DC-SIGN and L-SIGN (36–38), have also been proposed as candidate receptors for HCV. With several candidate receptors already identified and the current limitations to analyze their role in HCV entry, it is getting more and more difficult to propose a convincing model for HCV entry and explain its tropism to hepatic cells.
Upon appropriate activation of the viral surface glycoproteins occurs a dramatic refolding within the glycoproteins that results in the exposure of the fusion machinery. This conformational rearrangement is thought to release the energy necessary for the fusion process. Fusion activation of pH-independent viruses (e.g. most retroviruses) is triggered by highly ordered interactions of their glycoproteins with receptors to which they bind (39) and may occur at the cell surface. In contrast, the signal that initiates the conformational rearrangements of the pH-dependent viruses (e.g. influenza virus) is caused by acidification of the environment of the virion, implying that some cell surface receptors that mediate their binding internalize and traffic them to acid-pH cell compartments where membrane fusion occurs (28). Because of the structure of its genome and mechanisms of replication, HCV has been tentatively classified within its own genus, Hepacivirus, within the Flaviviridae family, which also comprises the Flavivirus and Pestivirus genera (40), and whose members, at least for the flaviviruses, exhibit pH-dependence in cell entry (41). Consistently, our results establish that inhibitors of endosomal-pH acidification reduce the infectivity of HCVpp to the same extent as that of pseudotype particles generated with glycoproteins from several pH-dependent viruses (Fig. 1), indicating that its cell surface receptor(s) should traffic cell-bound virions to endosomal compartments. Some of the different HCV receptor candidates are likely to fulfil this role. Although the LDL receptor was shown to mediate indirect HCV internalization, via binding to lipoproteins associated to virions, it is clear that alternative routes exist as suggested by studies with LDLr-deficient cells (18). The CD81 tetraspanin is likely involved in HCVpp infection because competition assays strongly inhibited the infectivity of HCVpp (14) and because HepG2 cells become permissive to infection only when they were engineered to express CD81 (Fig. 2). This is supported by the fact that none of the permissive cell types was found negative for CD81 expression (Table I). However, CD81 may have a very poor capacity to mediate virion internalization (42). Thus, CD81 may allow HCV attachment to the cell surface and subsequent interaction with a cell entry receptor, among which SR-B1 stands as a strong candidate. Indeed this receptor mediates selective uptake of a variety of macro-molecules such as high-density lipoprotein, LDL exchangeable apolipoproteins, protein-free lipid vesicles, and lipopolysaccharides (LPS) and is predominantly expressed in hepatocytes and steroidogenic tissues like adrenal glands and ovaries (43). Co-localization experiments demonstrated that SR-B1-bound LPS enters different intracellular compartments such as the Golgi complex and the endocytic recycling compartments after rapid endocytosis (44). This indicates that SR-B1 may have the capacity to traffic cell-bound virions to endosomal compartments wherein low-pH could activate the fusion properties of the HCV glycoproteins. Strain-specific differences in binding to either receptor have been detected (17, 27, 42, 45). E2 glycoproteins of the H77 strain, of genotype 1a, were found to bind more efficiently CD81 than E2 glycoproteins of genotype 1b, such as the J strain used in this study (27). Consistent with this finding, our results suggest that infectivity of HCVpp-1a is more efficiently inhibited by CD81-blocking antibodies (data not shown) and is restored to a level higher than HCVpp-1b in HepG2 cells expressing CD81 (Fig. 2). Nevertheless, despite a lower affinity to E2–1b glycoproteins, it is important to note that CD81 is critical for the infectivity of HCVpp of both genotypes as shown by results of genetic complementation assays in CD81-deficient hepato-carcinoma cells (Fig. 2) and by results of receptor competition assays (14). Hence, functional data, obtained with infectious pseudotype particles, may not completely match the data of binding assays and caution should be observed when interpreting the latter results. In contrast to CD81, there are no SR-B1-deficient hepato-carcinoma cells, thus limiting the experimental approaches to decipher the role of SR-B1 in HCV cell entry. Although over-expression of SR-B1 in 293 target cells resulted in significantly increased infectivity of HCVpp, the absolute titers of the latter virions remained low (Table I), most likely because of lack or insufficient expression of a factor predominantly expressed in hepatic cells. Therefore, formal demonstration of the involvement of SR-B1 in infection of hepato-carcinoma cells essentially relied on receptor competition assays using SR-B1 antibodies (Fig. 3) and on results obtained with the study of HVR1-deletion mutants (Fig. 4). The HVR1 segment, located at the amino terminus of the E2 glycoprotein, has been proposed to modulate accessibility to either CD81 or SR-B1 because its deletion from soluble E2 increased binding to CD81 (27) but abrogated binding to SR-B1 (17). Because infectivity of HVR1-deleted HCVpp was reduced by about 40-fold (Fig. 4B), these results indicate that loss of binding of E2 glycoproteins to either receptor can be compensated perhaps by interaction with another (co)-receptor. In agreement with this possibility, binding of soluble E2 glycoproteins could not be inhibited by more than 80% in Huh-7 or HepG2 cells, even at saturating concentration of SR-B1 antibodies (Fig. 3A), indicating interaction with other cell surface components. Alternatively and not exclusively, residual binding to SR-B1 may still occur with the HCVpp and may allow infection. That HCV may require very little amounts of receptors to mediate cell entry is consistent with recent results obtained with some other membrane-enveloped viruses (39, 46).
A growing body of evidence indicates that the DC-SIGN and L-SIGN lectins might play a role in HCV tropism. Both lectins, expressed in dendritic cells and in liver sinusoidal endothelial cells, bind high-mannose N-glycans of HCV E2 soluble glycoprotein, plasmatic HCV, and pseudotype particles (36–38). DC-SIGN has been shown to facilitate cell entry by enhancing cell attachment of several human pathogens like human immunodeficiency virus, Ebola virus, cytomegalovirus, and Dengue virus (47–51), thereby increasing the likelihood of interaction with specific entry receptors. Several studies have indeed reported alteration of dendritic cell functions in HCV-infected patients (52–54), and this may be a consequence of HCV interaction with DC-SIGN. Furthermore, because of its selective expression in liver sinusoidal endothelial cells, L-SIGN might have an important function in receptor-mediated targeting of HCV to the liver. Indeed, these cells play a key role in the initial uptake of viral pathogens into the liver, as shown for hepatitis B virus (55). A general mechanism by which hepatitis viruses, initially scavenged by liver sinusoidal endothelial cells are thereafter released to infect adjacent hepatocytes, the only cells capable of replicating these viruses, has been proposed (55). Thus HCV might be captured by L-SIGN after contamination by infected blood, resulting in concentration of virions in the liver and subsequent trans-luminal presentation to hepatocytes where it would then enter via use of specific receptors, including CD81 and SR-B1.
Although the capacity to bind DC-SIGN and L-SIGN may explain many features of HCV pathogenesis, it is unlikely that lectin-mediated capture of HCV is the sole determinant of hepato-tropism. Indeed L-SIGN is expressed in lymph nodes but is not expressed on hepatocytes, which represent the major target of infection. Furthermore, as shown elsewhere (16) and by us,2 expression of DC-SIGN in several non-permissive cells did not allow infection by HCVpp. Of note, all cells permissive to HCVpp co-express LDLr, CD81, and SR-B1 and are of liver origin (Table I). However, several cell lines of non-hepatic origin express all three cell surface molecules but are not or poorly permissive to HCVpp infection (Table I). These results imply that additional liver specific co-factor(s) are necessary for HCV entry. The nature of such molecule(s) is currently unknown, and the functional cloning of these additional molecules will be essential to decipher the early steps of HCV lifecycle.
|
FOOTNOTES |
|---|
* This work was supported by Agence Nationale pour la Recherche contre le SIDA (ANRS), the European Community (contracts QLK3 1999-00859 and QLRT-2000-01120), the Association pour la Recherche contre le Cancer (ARC), the Centre National de la Recherche Scientifique (CNRS), the Réseau National Hépatite C, and the Institut National de la Santé Et de la Recherche Médicale (INSERM, Action Thé-matique Concertée, Hépatite C). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
These authors have contributed equally to this study.
¶ Supported by a Marie Curie Fellowship from the European Community.
To whom correspondence should be addressed: Laboratoire de Vectorologie Rétrovirale et Thérapie Génique, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France. Tel.: 33-472-72-87-32; Fax: 33-472-72-80-80; E-mail: flcosset{at}ens-lyon.fr.
1 The abbreviations used are: HCV, hepatitis C virus; HCVpp, HCV pseudotype particles; E1, HCV glycoprotein 1; E2, HCV glycoprotein 2; SR-B1, scavenger receptor class B type 1; LDL, low density lipoprotein; LDLr, LDL receptor; MLV, murine leukemia virus; GFP, green fluorescent protein; VSV, vesicular stomatitis virus; VSV-G, VSV glycoprotein; CHO, Chinese hamster ovary; TU, transducing units; FACS, fluorescence-activated cell sorter; HVR1, hyper-variable region 1.
2 P. Y. Lozach, B. Bartosch, F.-L. Cosset, and R. Altmeyer, unpublished data.
|
ACKNOWLEDGMENTS |
|---|
We thank J. McKeating for providing the 9/27 anti-HVR1 monoclonal antibody.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONEXPERIMENTAL PROCEDURESRESULTSDISCUSSIONREFERENCES |
|---|
- Major, M. E., Rehermann, B., and Feinstone, S. M. (2001) in Fields Virology (Knipe, D. M., and Howley, P. M., eds) 4th Ed., Vol. 1, pp. 1127–1162, Lippincott Williams & Wilkins, Philadelphia, PA
- Lerat, H., Rumin, S., Habersetzer, F., Berby, F., Trabaud, M. A., Trepo, C., and Inchauspe, G. (1998) Blood 91, 3841–3849
[Abstract/Free Full Text] - Navas, M. C., Fuchs, A., Schvoerer, E., Bohbot, A., Aubertin, A. M., and Stoll-Keller, F. (2002) J. Med. Virol. 67, 152–161[CrossRef][Medline] [Order article via Infotrieve]
- Lindenbach, B. D., and Rice, C. M. (2001) in Fields Virology (Knipe, D. M., and Howley, P. M., eds, 4th Ed., pp. 991–1042, Lippincott Williams & Wilkins, Philadelphia, PA
- Baumert, T. F., Ito, S., Wong, D. T., and Liang, T. J. (1998) J. Virol. 72, 3827–3836
[Abstract/Free Full Text] - Owsianka, A., Clayton, R. F., Loomis-Price, L. D., McKeating, J. A., and Patel, A. H. (2001) J. Gen. Virol. 82, 1877–1883
[Abstract/Free Full Text] - Triyatni, M., Saunier, B., Maruvada, P., Davis, A. R., Ulianich, L., Heller, T., Patel, A., Kohn, L. D., and Liang, T. J. (2002) J. Virol. 76, 9335–9344
[Abstract/Free Full Text] - Wellnitz, S., Klumpp, B., Barth, H., Ito, S., Depla, E., Dubuisson, J., Blum, H. E., and Baumert, T. F. (2002) J. Virol. 76, 1181–1193
[Abstract/Free Full Text] - Buonocore, L., Blight, K. J., Rice, C. M., and Rose, J. K. (2002) J. Virol. 76, 6865–6872
[Abstract/Free Full Text] - Flint, M., Thomas, J. M., Maidens, C. M., Shotton, C., Levy, S., Barclay, W. S., and McKeating, J. A. (1999) J. Virol. 73, 6782–6790
[Abstract/Free Full Text] - Lagging, L. M., Meyer, K., Owens, R. J., and Ray, R. (1998) J. Virol. 72, 3539–3546
[Abstract/Free Full Text] - Matsuura, Y., Tani, H., Suzuki, K., Kimura-Someya, T., Suzuki, R., Aizaki, H., Ishii, K., Moriishi, K., Robison, C. S., Whitt, M. A., and Miyamura, T. (2001) Virology 286, 263–275[CrossRef][Medline] [Order article via Infotrieve]
- Takikawa, S., Ishii, K., Aizaki, H., Suzuki, T., Asakura, H., Matsuura, Y., and Miyamura, T. (2000) J. Virol. 74, 5066–5074
[Abstract/Free Full Text] - Bartosch, B., Dubuisson, J., and Cosset, F. L. (2003) J. Exp. Med. 197, 633–642
[Abstract/Free Full Text] - Drummer, H. E., Maerz, A., and Poumbourios, P. (2003) FEBS Lett. 546, 385–390[CrossRef][Medline] [Order article via Infotrieve]
- Hsu, M., Zhang, J., Flint, M., Logvinoff, C., Cheng-Mayer, C., Rice, C. M., and McKeating, J. A. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 7271–7276
[Abstract/Free Full Text] - Scarselli, E., Ansuini, H., Cerino, R., Roccasecca, R., Acali, S., Filocamo, G., Traboni, C., Nicosia, A., Cortese, R., and Vitelli, A. (2002) EMBO J. 21, 5017–5025[CrossRef][Medline] [Order article via Infotrieve]
- Agnello, V., Abel, G., Elfahal, M., Knight, G. B., and Zhang, Q. X. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 12766–12771
[Abstract/Free Full Text] - Pileri, P., Uematsu, Y., Campagnoli, S., Galli, G., Falugi, F., Petracca, R., Weiner, A. J., Houghton, M., Rosa, D., Grandi, G., and Abrignani, S. (1998) Science 282, 938–941
[Abstract/Free Full Text] - Nègre, D., Mangeot, P., Duisit, G., Blanchard, S., Vidalain, P., Leissner, P., Winter, A., Rabourdin-Combe, C., Mehtali, M., Moullier, P., Darlix, J.-L., and Cosset, F.-L. (2000) Gene. Ther. 7, 1613–1623[CrossRef][Medline] [Order article via Infotrieve]
- Sandrin, V., Boson, B., Salmon, P., Gay, W., Nègre, D., LeGrand, R., Trono, D., and Cosset, F.-L. (2002) Blood 100, 823–832
[Abstract/Free Full Text] - Nakabayashi, H., Taketa, K., Miyano, K., Yamane, T., and Sato, J. (1982) Cancer Res. 42, 3858–3863
[Abstract/Free Full Text] - Calvo, D., and Vega, M. A. (1993) J. Biol. Chem. 268, 18929–18935
[Abstract/Free Full Text] - Flint, M., Maidens, C., Loomis-Price, L. D., Shotton, C., Dubuisson, J., Monk, P., Higginbottom, A., Levy, S., and McKeating, J. A. (1999) J. Virol. 73, 6235–6244
[Abstract/Free Full Text] - Dubuisson, J., Hsu, H. H., Cheung, R. C., Greenberg, H. B., Russell, D. G., and Rice, C. M. (1994) J. Virol. 68, 6147–6160
[Abstract/Free Full Text] - Zucchelli, S., Roccasecca, R., Meola, A., Ercole, B. B., Tafi, R., Dubuisson, J., Galfre, G., Cortese, R., and Nicosia, A. (2001) Hepatology 33, 692–703[CrossRef][Medline] [Order article via Infotrieve]
- Roccasecca, R., Ansuini, H., Vitelli, A., Meola, A., Scarselli, E., Acali, S., Pezzanera, M., Ercole, B. B., McKeating, J., Yagnik, A., Lahm, A., Tramontano, A., Cortese, R., and Nicosia, A. (2003) J. Virol. 77, 1856–1867
[Abstract/Free Full Text] - Sieczkarski, S. B., and Whittaker, G. R. (2002) J. Gen. Virol. 83, 1535–1545
[Abstract/Free Full Text] - McClure, M. O., Sommerfelt, M. A., Marsh, M., and Weiss, R. A. (1990) J. Gen. Virol. 71, 767–773
[Abstract/Free Full Text] - Monazahian, M., Bohme, I., Bonk, S., Koch, A., Scholz, C., Grethe, S., and Thomssen, R. (1999) J. Med. Virol. 57, 223–229[CrossRef][Medline] [Order article via Infotrieve]
- Andre, P., Komurian-Pradel, F., Deforges, S., Perret, M., Berland, J. L., Sodoyer, M., Pol, S., Brechot, C., Paranhos-Baccala, G., and Lotteau, V. (2002) J. Virol. 76, 6919–6928
[Abstract/Free Full Text] - Yagnik, A. T., Lahm, A., Meola, A., Roccasecca, R. M., Ercole, B. B., Nicosia, A., and Tramontano, A. (2000) Proteins 40, 355–366[CrossRef][Medline] [Order article via Infotrieve]
- Penin, F., Combet, C., Germanidis, G., Frainais, P. O., Deleage, G., and Pawlotsky, J. M. (2001) J. Virol. 75, 5703–5710
[Abstract/Free Full Text] - Forns, X., Thimme, R., Govindarajan, S., Emerson, S. U., Purcell, R. H., Chisari, F. V., and Bukh, J. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 13318–13323
[Abstract/Free Full Text] - Flint, M., Dubuisson, J., Maidens, C., Harrop, R., Guile, G. R., Borrow, P., and McKeating, J. A. (2000) J. Virol. 74, 702–709
[Abstract/Free Full Text] - Gardner, J. P., Durso, R. J., Arrigale, R. R., Donovan, G. P., Maddon, P. J., Dragic, T., and Olson, W. C. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 4498–4503
[Abstract/Free Full Text] - Lozach, P. Y., Lortat-Jacob, H., De Lacroix De Lavalette, A., Staropoli, I., Foung, S., Amara, A., Houles, C., Fieschi, F., Schwartz, Virelizier, J. L., Arenzana-Seisdedos, F., and Altmeyer, R. (2003) J. Biol. Chem.
- Pohlmann, S., Zhang, J., Baribaud, F., Chen, Z., Leslie, G. J., Lin, G., Granelli-Piperno, A., Doms, R. W., Rice, C. M., and McKeating, J. A. (2003) J. Virol. 77, 4070–4080
[Abstract/Free Full Text] - Lavillette, D., Ruggieri, A., Boson, B., Maurice, M., and Cosset, F.-L. (2002) J. Virol. 76, 9673–9685
[Abstract/Free Full Text] - Robertson, B., Myers, G., Howard, C., Brettin, T., Bukh, J., Gaschen, B., Gojobori, T., Maertens, G., Mizokami, M., Nainan, O., Netesov, S., Nishioka, K., Shin-i, T., Simmonds, P., Smith, D., Stuyver, L., and Weiner, A. (1998) Arch. Virol. 143, 2493–2503[CrossRef][Medline] [Order article via Infotrieve]
- Heinz, F. X., and Allison, S. L. (2001) Curr. Opin. Microbiol. 4, 450–455[CrossRef][Medline] [Order article via Infotrieve]
- Petracca, R., Falugi, F., Galli, G., Norais, N., Rosa, D., Campagnoli, S., Burgio, V., Di Stasio, E., Giardina, B., Houghton, M., Abrignani, S., and Grandi, G. (2000) J. Virol. 74, 4824–4830
[Abstract/Free Full Text] - Krieger, M. (2001) J. Clin. Invest. 108, 793–797[CrossRef][Medline] [Order article via Infotrieve]
- Vishnyakova, T. G., Bocharov, A. V., Baranova, I. N., Chen, Z., Remaley, A. T., Csako, G., Eggerman, T. L., and Patterson, A. P. (2003) J. Biol. Chem.
- Shaw, M. L., McLauchlan, J., Mills, P. R., Patel, A. H., and McCruden, E. A. (2003) J. Med. Virol. 70, 361–372[CrossRef][Medline] [Order article via Infotrieve]
- Wensel, D. L., Li, W., and Cunningham, J. M. (2003) J. Virol. 77, 3460–3469
[Abstract/Free Full Text] - Alvarez, C. P., Lasala, F., Carrillo, J., Muniz, O., Corbi, A. L., and Delgado, R. (2002) J. Virol. 76, 6841–6844
[Abstract/Free Full Text] - Geijtenbeek, T. B., Kwon, D. S., Torensma, R., van Vliet, S. J., van Duijnhoven, G. C., Middel, J., Cornelissen, I. L., Nottet, H. S., KewalRamani, V. N., Littman, D. R., Figdor, C. G., and van Kooyk, Y. (2000) Cell 100, 587–597[CrossRef][Medline] [Order article via Infotrieve]
- Halary, F., Amara, A., Lortat-Jacob, H., Messerle, M., Delaunay, T., Houles, C., Fieschi, F., Arenzana-Seisdedos, F., Moreau, J. F., and Dechanet-Merville, J. (2002) Immunity 17, 653–664[CrossRef][Medline] [Order article via Infotrieve]
- Navarro-Sanchez, E., Altmeyer, R., Amara, A., Schwartz, O., Fieschi, F., Virelizier, J. L., Arenzana-Seisdedos, F., and Despres, P. (2003) EMBO Rep. 4, 1–6[Medline] [Order article via Infotrieve]
- Tassaneetrithep, B., Burgess, T. H., Granelli-Piperno, A., Trumpfheller, C., Finke, J., Sun, W., Eller, M. A., Pattanapanyasat, K., Sarasombath, S., Birx, D. L., Steinman, R. M., Schlesinger, S., and Marovich, M. A. (2003) J. Exp. Med. 197, 823–829
[Abstract/Free Full Text] - Akbar, S. M., Horiike, N., Onji, M., and Hino, O. (2001) Intervirology 44, 199–208[CrossRef][Medline] [Order article via Infotrieve]
- Auffermann-Gretzinger, S., Keeffe, E. B., and Levy, S. (2001) Blood 97, 3171–3176
[Abstract/Free Full Text] - Bain, C., Fatmi, A., Zoulim, F., Zarski, J. P., Trepo, C., and Inchauspe, G. (2001) Gastroenterology 120, 512–524[CrossRef][Medline] [Order article via Infotrieve]
- Breiner, K. M., Schaller, H., and Knolle, P. A. (2001) Hepatology 34, 803–808[CrossRef][Medline] [Order article via Infotrieve]
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Bungyoku, I. Shoji, T. Makine, T. Adachi, K. Hayashida, M. Nagano-Fujii, Y.-H. Ide, L. Deng, and H. Hotta Efficient production of infectious hepatitis C virus with adaptive mutations in cultured hepatoma cells J. Gen. Virol., July 1, 2009; 90(7): 1681 - 1691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Haid, T. Pietschmann, and E.-I. Pecheur Low pH-dependent Hepatitis C Virus Membrane Fusion Depends on E2 Integrity, Target Lipid Composition, and Density of Virus Particles J. Biol. Chem., June 26, 2009; 284(26): 17657 - 17667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Mee, H. J. Harris, M. J. Farquhar, G. Wilson, G. Reynolds, C. Davis, S. C. D. van IJzendoorn, P. Balfe, and J. A. McKeating Polarization Restricts Hepatitis C Virus Entry into HepG2 Hepatoma Cells J. Virol., June 15, 2009; 83(12): 6211 - 6221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Burlone and A. Budkowska Hepatitis C virus cell entry: role of lipoproteins and cellular receptors J. Gen. Virol., May 1, 2009; 90(5): 1055 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Stamataki, C. Shannon-Lowe, J. Shaw, D. Mutimer, A. B. Rickinson, J. Gordon, D. H. Adams, P. Balfe, and J. A. McKeating Hepatitis C virus association with peripheral blood B lymphocytes potentiates viral infection of liver-derived hepatoma cells Blood, January 15, 2009; 113(3): 585 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J M Timpe and J A McKeating Hepatitis C virus entry: possible targets for therapy Gut, December 1, 2008; 57(12): 1728 - 1737. [Full Text] [PDF]
|
|
|
|
|
|
M. Brazzoli, A. Bianchi, S. Filippini, A. Weiner, Q. Zhu, M. Pizza, and S. Crotta CD81 Is a Central Regulator of Cellular Events Required for Hepatitis C Virus Infection of Human Hepatocytes J. Virol., September 1, 2008; 82(17): 8316 - 8329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Farquhar, H. J. Harris, M. Diskar, S. Jones, C. J. Mee, S. U. Nielsen, C. L. Brimacombe, S. Molina, G. L. Toms, P. Maurel, et al. Protein Kinase A-Dependent Step(s) in Hepatitis C Virus Entry and Infectivity J. Virol., September 1, 2008; 82(17): 8797 - 8811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Harris, M. J. Farquhar, C. J. Mee, C. Davis, G. M. Reynolds, A. Jennings, K. Hu, F. Yuan, H. Deng, S. G. Hubscher, et al. CD81 and Claudin 1 Coreceptor Association: Role in Hepatitis C Virus Entry J. Virol., May 15, 2008; 82(10): 5007 - 5020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jones and J. S Owen How does interferon inhibit HCV cell entry? Gut, May 1, 2008; 57(5): 573 - 574. [Full Text] [PDF]
|
|
|
|
|
|
K Murao, H Imachi, X Yu, W M Cao, T Nishiuchi, K Chen, J Li, R A M Ahmed, N C W Wong, and T Ishida Interferon {alpha} decreases expression of human scavenger receptor class BI, a possible HCV receptor in hepatocytes Gut, May 1, 2008; 57(5): 664 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Owsianka, A. W. Tarr, Z.-Y. Keck, T.-K. Li, J. Witteveldt, R. Adair, S. K. H. Foung, J. K. Ball, and A. H. Patel Broadly neutralizing human monoclonal antibodies to the hepatitis C virus E2 glycoprotein J. Gen. Virol., March 1, 2008; 89(3): 653 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Gastaminza, G. Cheng, S. Wieland, J. Zhong, W. Liao, and F. V. Chisari Cellular Determinants of Hepatitis C Virus Assembly, Maturation, Degradation, and Secretion J. Virol., March 1, 2008; 82(5): 2120 - 2129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. von Hahn and C. M. Rice Hepatitis C Virus Entry J. Biol. Chem., February 15, 2008; 283(7): 3689 - 3693. [Full Text] [PDF]
|
|
|
|
|
|
S. Molina, V. Castet, L. Pichard-Garcia, C. Wychowski, E. Meurs, J.-M. Pascussi, C. Sureau, J.-M. Fabre, A. SaCunha, D. Larrey, et al. Serum-Derived Hepatitis C Virus Infection of Primary Human Hepatocytes Is Tetraspanin CD81 Dependent J. Virol., January 1, 2008; 82(1): 569 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-S. Chang, J. Jiang, Z. Cai, and G. Luo Human Apolipoprotein E Is Required for Infectivity and Production of Hepatitis C Virus in Cell Culture J. Virol., December 15, 2007; 81(24): 13783 - 13793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dreux, B. Boson, S. Ricard-Blum, J. Molle, D. Lavillette, B. Bartosch, E.-I. Pecheur, and F.-L. Cosset The Exchangeable Apolipoprotein ApoC-I Promotes Membrane Fusion of Hepatitis C Virus J. Biol. Chem., November 2, 2007; 282(44): 32357 - 32369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lavillette, E.-I. Pecheur, P. Donot, J. Fresquet, J. Molle, R. Corbau, M. Dreux, F. Penin, and F.-L. Cosset Characterization of Fusion Determinants Points to the Involvement of Three Discrete Regions of Both E1 and E2 Glycoproteins in the Membrane Fusion Process of Hepatitis C Virus J. Virol., August 15, 2007; 81(16): 8752 - 8765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tani, Y. Komoda, E. Matsuo, K. Suzuki, I. Hamamoto, T. Yamashita, K. Moriishi, K. Fujiyama, T. Kanto, N. Hayashi, et al. Replication-Competent Recombinant Vesicular Stomatitis Virus Encoding Hepatitis C Virus Envelope Proteins J. Virol., August 15, 2007; 81(16): 8601 - 8612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Gottwein and J. Bukh Hepatitis C virus host cell interactions uncovered PNAS, August 14, 2007; 104(33): 13215 - 13216. [Full Text] [PDF]
|
|
|
|
|
|
M. T. Catanese, R. Graziani, T. von Hahn, M. Moreau, T. Huby, G. Paonessa, C. Santini, A. Luzzago, C. M. Rice, R. Cortese, et al. High-Avidity Monoclonal Antibodies against the Human Scavenger Class B Type I Receptor Efficiently Block Hepatitis C Virus Infection in the Presence of High-Density Lipoprotein J. Virol., August 1, 2007; 81(15): 8063 - 8071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Falkowska, F. Kajumo, E. Garcia, J. Reinus, and T. Dragic Hepatitis C Virus Envelope Glycoprotein E2 Glycans Modulate Entry, CD81 Binding, and Neutralization J. Virol., August 1, 2007; 81(15): 8072 - 8079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Helle, A. Goffard, V. Morel, G. Duverlie, J. McKeating, Z.-Y. Keck, S. Foung, F. Penin, J. Dubuisson, and C. Voisset The Neutralizing Activity of Anti-Hepatitis C Virus Antibodies Is Modulated by Specific Glycans on the E2 Envelope Protein J. Virol., August 1, 2007; 81(15): 8101 - 8111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Randall, M. Panis, J. D. Cooper, T. L. Tellinghuisen, K. E. Sukhodolets, S. Pfeffer, M. Landthaler, P. Landgraf, S. Kan, B. D. Lindenbach, et al. Cellular cofactors affecting hepatitis C virus infection and replication PNAS, July 31, 2007; 104(31): 12884 - 12889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Cai, L. Cai, J. Jiang, K.-S. Chang, D. R. van der Westhuyzen, and G. Luo Human Serum Amyloid A Protein Inhibits Hepatitis C Virus Entry into Cells J. Virol., June 1, 2007; 81(11): 6128 - 6133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Akazawa, T. Date, K. Morikawa, A. Murayama, M. Miyamoto, M. Kaga, H. Barth, T. F. Baumert, J. Dubuisson, and T. Wakita CD81 Expression Is Important for the Permissiveness of Huh7 Cell Clones for Heterogeneous Hepatitis C Virus Infection J. Virol., May 15, 2007; 81(10): 5036 - 5045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Schaller, N. Appel, G. Koutsoudakis, S. Kallis, V. Lohmann, T. Pietschmann, and R. Bartenschlager Analysis of Hepatitis C Virus Superinfection Exclusion by Using Novel Fluorochrome Gene-Tagged Viral Genomes J. Virol., May 1, 2007; 81(9): 4591 - 4603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Tscherne, M. J. Evans, T. von Hahn, C. T. Jones, Z. Stamataki, J. A. McKeating, B. D. Lindenbach, and C. M. Rice Superinfection Exclusion in Cells Infected with Hepatitis C Virus J. Virol., April 15, 2007; 81(8): 3693 - 3703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Grove, T. Huby, Z. Stamataki, T. Vanwolleghem, P. Meuleman, M. Farquhar, A. Schwarz, M. Moreau, J. S. Owen, G. Leroux-Roels, et al. Scavenger Receptor BI and BII Expression Levels Modulate Hepatitis C Virus Infectivity J. Virol., April 1, 2007; 81(7): 3162 - 3169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ciczora, N. Callens, F. Penin, E.-I. Pecheur, and J. Dubuisson Transmembrane Domains of Hepatitis C Virus Envelope Glycoproteins: Residues Involved in E1E2 Heterodimerization and Involvement of These Domains in Virus Entry J. Virol., March 1, 2007; 81(5): 2372 - 2381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-Y. Keck, J. Xia, Z. Cai, T.-K. Li, A. M. Owsianka, A. H. Patel, G. Luo, and S. K. H. Foung Immunogenic and Functional Organization of Hepatitis C Virus (HCV) Glycoprotein E2 on Infectious HCV Virions J. Virol., January 15, 2007; 81(2): 1043 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Kapadia, H. Barth, T. Baumert, J. A. McKeating, and F. V. Chisari Initiation of Hepatitis C Virus Infection Is Dependent on Cholesterol and Cooperativity between CD81 and Scavenger Receptor B Type I J. Virol., January 1, 2007; 81(1): 374 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Breiman, D. Vitour, M. Vilasco, C. Ottone, S. Molina, L. Pichard, C. Fournier, D. Delgrange, P. Charneau, G. Duverlie, et al. A hepatitis C virus (HCV) NS3/4A protease-dependent strategy for the identification and purification of HCV-infected cells J. Gen. Virol., December 1, 2006; 87(12): 3587 - 3598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Meertens, C. Bertaux, and T. Dragic Hepatitis C Virus Entry Requires a Critical Postinternalization Step and Delivery to Early Endosomes via Clathrin-Coated Vesicles J. Virol., December 1, 2006; 80(23): 11571 - 11578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mannova, R. Fang, H. Wang, B. Deng, M. W. McIntosh, S. M. Hanash, and L. Beretta Modification of Host Lipid Raft Proteome upon Hepatitis C Virus Replication Mol. Cell. Proteomics, December 1, 2006; 5(12): 2319 - 2325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Flint, T. von Hahn, J. Zhang, M. Farquhar, C. T. Jones, P. Balfe, C. M. Rice, and J. A. McKeating Diverse CD81 Proteins Support Hepatitis C Virus Infection J. Virol., November 15, 2006; 80(22): 11331 - 11342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhong, P. Gastaminza, J. Chung, Z. Stamataki, M. Isogawa, G. Cheng, J. A. McKeating, and F. V. Chisari Persistent Hepatitis C Virus Infection In Vitro: Coevolution of Virus and Host J. Virol., November 15, 2006; 80(22): 11082 - 11093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Vishnyakova, R. Kurlander, A. V. Bocharov, I. N. Baranova, Z. Chen, M. S. Abu-Asab, M. Tsokos, D. Malide, F. Basso, A. Remaley, et al. CLA-1 and its splicing variant CLA-2 mediate bacterial adhesion and cytosolic bacterial invasion in mammalian cells PNAS, November 7, 2006; 103(45): 16888 - 16893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Barth, E. K. Schnober, F. Zhang, R. J. Linhardt, E. Depla, B. Boson, F.-L. Cosset, A. H. Patel, H. E. Blum, and T. F. Baumert Viral and Cellular Determinants of the Hepatitis C Virus Envelope-Heparan Sulfate Interaction J. Virol., November 1, 2006; 80(21): 10579 - 10590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Falkowska, R. J. Durso, J. P. Gardner, E. G. Cormier, R. A. Arrigale, R. N. Ogawa, G. P. Donovan, P. J. Maddon, W. C. Olson, and T. Dragic L-SIGN (CD209L) isoforms differently mediate trans-infection of hepatoma cells by hepatitis C virus pseudoparticles J. Gen. Virol., September 1, 2006; 87(9): 2571 - 2576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Codran, C. Royer, D. Jaeck, M. Bastien-Valle, T. F. Baumert, M. P. Kieny, C. A. Pereira, and J.-P. Martin Entry of hepatitis C virus pseudotypes into primary human hepatocytes by clathrin-dependent endocytosis J. Gen. Virol., September 1, 2006; 87(9): 2583 - 2593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Owsianka, J. M. Timms, A. W. Tarr, R. J. P. Brown, T. P. Hickling, A. Szwejk, K. Bienkowska-Szewczyk, B. J. Thomson, A. H. Patel, and J. K. Ball Identification of conserved residues in the e2 envelope glycoprotein of the hepatitis C virus that are critical for CD81 binding. J. Virol., September 1, 2006; 80(17): 8695 - 8704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Drummer, I. Boo, A. L. Maerz, and P. Poumbourios A conserved gly436-trp-leu-ala-gly-leu-phe-tyr motif in hepatitis C virus glycoprotein e2 is a determinant of CD81 binding and viral entry. J. Virol., August 1, 2006; 80(16): 7844 - 7853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Blanchard, S. Belouzard, L. Goueslain, T. Wakita, J. Dubuisson, C. Wychowski, and Y. Rouille Hepatitis C Virus Entry Depends on Clathrin-Mediated Endocytosis J. Virol., July 15, 2006; 80(14): 6964 - 6972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gesierich, I. Berezovskiy, E. Ryschich, and M. Zoller Systemic Induction of the Angiogenesis Switch by the Tetraspanin D6.1A/CO-029. Cancer Res., July 15, 2006; 66(14): 7083 - 7094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dreux, T. Pietschmann, C. Granier, C. Voisset, S. Ricard-Blum, P.-E. Mangeot, Z. Keck, S. Foung, N. Vu-Dac, J. Dubuisson, et al. High Density Lipoprotein Inhibits Hepatitis C Virus-neutralizing Antibodies by Stimulating Cell Entry via Activation of the Scavenger Receptor BI J. Biol. Chem., July 7, 2006; 281(27): 18285 - 18295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. K. Lai, P. J. Sun, J. Zhang, A. Jennings, P. F. Lalor, S. Hubscher, J. A. McKeating, and D. H. Adams Expression of DC-SIGN and DC-SIGNR on Human Sinusoidal Endothelium: A Role for Capturing Hepatitis C Virus Particles Am. J. Pathol., July 1, 2006; 169(1): 200 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Koutsoudakis, A. Kaul, E. Steinmann, S. Kallis, V. Lohmann, T. Pietschmann, and R. Bartenschlager Characterization of the early steps of hepatitis C virus infection by using luciferase reporter viruses. J. Virol., June 1, 2006; 80(11): 5308 - 5320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Silvie, S. Charrin, M. Billard, J.-F. Franetich, K. L. Clark, G.-J. van Gemert, R. W. Sauerwein, F. Dautry, C. Boucheix, D. Mazier, et al. Cholesterol contributes to the organization of tetraspanin-enriched microdomains and to CD81-dependent infection by malaria sporozoites J. Cell Sci., May 15, 2006; 119(10): 1992 - 2002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Cocquerel, C. Voisset, and J. Dubuisson Hepatitis C virus entry: potential receptors and their biological functions. J. Gen. Virol., May 1, 2006; 87(Pt 5): 1075 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bertaux and T. Dragic Different domains of CD81 mediate distinct stages of hepatitis C virus pseudoparticle entry. J. Virol., May 1, 2006; 80(10): 4940 - 4948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D A Price, M F Bassendine, S M Norris, C Golding, G L Toms, M L Schmid, C M Morris, A D Burt, and P T Donaldson Apolipoprotein {varepsilon}3 allele is associated with persistent hepatitis C virus infection Gut, May 1, 2006; 55(5): 715 - 718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Eren, D. Landstein, D. Terkieltaub, O. Nussbaum, A. Zauberman, J. Ben-Porath, J. Gopher, R. Buchnick, R. Kovjazin, Z. Rosenthal-Galili, et al. Preclinical Evaluation of Two Neutralizing Human Monoclonal Antibodies against Hepatitis C Virus (HCV): a Potential Treatment To Prevent HCV Reinfection in Liver Transplant Patients J. Virol., March 15, 2006; 80(6): 2654 - 2664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lavillette, B. Bartosch, D. Nourrisson, G. Verney, F.-L. Cosset, F. Penin, and E.-I. Pecheur Hepatitis C Virus Glycoproteins Mediate Low pH-dependent Membrane Fusion with Liposomes J. Biol. Chem., February 17, 2006; 281(7): 3909 - 3917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Tscherne, C. T. Jones, M. J. Evans, B. D. Lindenbach, J. A. McKeating, and C. M. Rice Time- and Temperature-Dependent Activation of Hepatitis C Virus for Low-pH-Triggered Entry J. Virol., February 15, 2006; 80(4): 1734 - 1741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kobayashi, M. C. Bennett, T. Bercot, and I. R. Singh Functional Analysis of Hepatitis C Virus Envelope Proteins, Using a Cell-Cell Fusion Assay J. Virol., February 15, 2006; 80(4): 1817 - 1825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Sandrin and F.-L. Cosset Intracellular Versus Cell Surface Assembly of Retroviral Pseudotypes Is Determined by the Cellular Localization of the Viral Glycoprotein, Its Capacity to Interact with Gag, and the Expression of the Nef Protein J. Biol. Chem., January 6, 2006; 281(1): 528 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Callens, Y. Ciczora, B. Bartosch, N. Vu-Dac, F.-L. Cosset, J.-M. Pawlotsky, F. Penin, and J. Dubuisson Basic Residues in Hypervariable Region 1 of Hepatitis C Virus Envelope Glycoprotein E2 Contribute to Virus Entry J. Virol., December 15, 2005; 79(24): 15331 - 15341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Griffin, D. Clarke, C. McCormick, D. Rowlands, and M. Harris Signal Peptide Cleavage and Internal Targeting Signals Direct the Hepatitis C Virus p7 Protein to Distinct Intracellular Membranes J. Virol., December 15, 2005; 79(24): 15525 - 15536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Sandrin, P. Boulanger, F. Penin, C. Granier, F.-L. Cosset, and B. Bartosch Assembly of functional hepatitis C virus glycoproteins on infectious pseudoparticles occurs intracellularly and requires concomitant incorporation of E1 and E2 glycoproteins J. Gen. Virol., December 1, 2005; 86(12): 3189 - 3199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-Y. Keck, T.-K. Li, J. Xia, B. Bartosch, F.-L. Cosset, J. Dubuisson, and S. K. H. Foung Analysis of a Highly Flexible Conformational Immunogenic Domain A in Hepatitis C Virus E2 J. Virol., November 1, 2005; 79(21): 13199 - 13208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Yamada, M. Montoya, C. G. Schuettler, T. P. Hickling, A. W. Tarr, A. Vitelli, J. Dubuisson, A. H. Patel, J. K. Ball, and P. Borrow Analysis of the binding of hepatitis C virus genotype 1a and 1b E2 glycoproteins to peripheral blood mononuclear cell subsets J. Gen. Virol., September 1, 2005; 86(9): 2507 - 2512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Martin, D. M. Roth, D. A. Jans, C. W. Pouton, L. J. Partridge, P. N. Monk, and G. W. Moseley Tetraspanins in Viral Infections: a Fundamental Role in Viral Biology? J. Virol., September 1, 2005; 79(17): 10839 - 10851. [Full Text] [PDF]
|
|
|
|
|
|
A. Owsianka, A. W. Tarr, V. S. Juttla, D. Lavillette, B. Bartosch, F.-L. Cosset, J. K. Ball, and A. H. Patel Monoclonal Antibody AP33 Defines a Broadly Neutralizing Epitope on the Hepatitis C Virus E2 Envelope Glycoprotein J. Virol., September 1, 2005; 79(17): 11095 - 11104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lecot, S. Belouzard, J. Dubuisson, and Y. Rouille Bovine Viral Diarrhea Virus Entry Is Dependent on Clathrin-Mediated Endocytosis J. Virol., August 15, 2005; 79(16): 10826 - 10829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Lindenbach, M. J. Evans, A. J. Syder, B. Wolk, T. L. Tellinghuisen, C. C. Liu, T. Maruyama, R. O. Hynes, D. R. Burton, J. A. McKeating, et al. Complete Replication of Hepatitis C Virus in Cell Culture Science, July 22, 2005; 309(5734): 623 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. P. Brown, V. S. Juttla, A. W. Tarr, R. Finnis, W. L. Irving, S. Hemsley, D. R. Flower, P. Borrow, and J. K. Ball Evolutionary dynamics of hepatitis C virus envelope genes during chronic infection J. Gen. Virol., July 1, 2005; 86(7): 1931 - 1942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Bartosch, G. Verney, M. Dreux, P. Donot, Y. Morice, F. Penin, J.-M. Pawlotsky, D. Lavillette, and F.-L. Cosset An Interplay between Hypervariable Region 1 of the Hepatitis C Virus E2 Glycoprotein, the Scavenger Receptor BI, and High-Density Lipoprotein Promotes both Enhancement of Infection and Protection against Neutralizing Antibodies J. Virol., July 1, 2005; 79(13): 8217 - 8229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Barth, R. Cerino, M. Arcuri, M. Hoffmann, P. Schurmann, M. I. Adah, B. Gissler, X. Zhao, V. Ghisetti, B. Lavezzo, et al. Scavenger Receptor Class B Type I and Hepatitis C Virus Infection of Primary Tupaia Hepatocytes J. Virol., May 1, 2005; 79(9): 5774 - 5785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Voisset, N. Callens, E. Blanchard, A. Op De Beeck, J. Dubuisson, and N. Vu-Dac High Density Lipoproteins Facilitate Hepatitis C Virus Entry through the Scavenger Receptor Class B Type I J. Biol. Chem., March 4, 2005; 280(9): 7793 - 7799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Stein, P. Primakoff, and D. Myles Sperm-egg fusion: events at the plasma membrane J. Cell Sci., December 15, 2004; 117(26): 6269 - 6274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Cormier, R. J. Durso, F. Tsamis, L. Boussemart, C. Manix, W. C. Olson, J. P. Gardner, and T. Dragic L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus PNAS, September 28, 2004; 101(39): 14067 - 14072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-Y. Keck, A. Op De Beeck, K. G. Hadlock, J. Xia, T.-K. Li, J. Dubuisson, and S. K. H. Foung Hepatitis C Virus E2 Has Three Immunogenic Domains Containing Conformational Epitopes with Distinct Properties and Biological Functions J. Virol., September 1, 2004; 78(17): 9224 - 9232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. McKeating, L. Q. Zhang, C. Logvinoff, M. Flint, J. Zhang, J. Yu, D. Butera, D. D. Ho, L. B. Dustin, C. M. Rice, et al. Diverse Hepatitis C Virus Glycoproteins Mediate Viral Infection in a CD81-Dependent Manner J. Virol., August 15, 2004; 78(16): 8496 - 8505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-Y. Lozach, A. Amara, B. Bartosch, J.-L. Virelizier, F. Arenzana-Seisdedos, F.-L. Cosset, and R. Altmeyer C-type Lectins L-SIGN and DC-SIGN Capture and Transmit Infectious Hepatitis C Virus Pseudotype Particles J. Biol. Chem., July 30, 2004; 279(31): 32035 - 32045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Drummer and P. Poumbourios Hepatitis C Virus Glycoprotein E2 Contains a Membrane-proximal Heptad Repeat Sequence That Is Essential for E1E2 Glycoprotein Heterodimerization and Viral Entry J. Biol. Chem., July 16, 2004; 279(29): 30066 - 30072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-H. Heo, J.-H. Chang, J.-W. Lee, S. K. H. Foung, J. Dubuisson, and C.-Y. Kang Incomplete Humoral Immunity against Hepatitis C Virus Is Linked with Distinct Recognition of Putative Multiple Receptors by E2 Envelope Glycoprotein J. Immunol., July 1, 2004; 173(1): 446 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Cormier, F. Tsamis, F. Kajumo, R. J. Durso, J. P. Gardner, and T. Dragic CD81 is an entry coreceptor for hepatitis C virus PNAS, May 11, 2004; 101(19): 7270 - 7274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Op De Beeck, C. Voisset, B. Bartosch, Y. Ciczora, L. Cocquerel, Z. Keck, S. Foung, F.-L. Cosset, and J. Dubuisson Characterization of Functional Hepatitis C Virus Envelope Glycoproteins J. Virol., March 15, 2004; 78(6): 2994 - 3002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Bartosch, J. Bukh, J.-C. Meunier, C. Granier, R. E. Engle, W. C. Blackwelder, S. U. Emerson, F.-L. Cosset, and R. H. Purcell In vitro assay for neutralizing antibody to hepatitis C virus: Evidence for broadly conserved neutralization epitopes PNAS, November 25, 2003; 100(24): 14199 - 14204. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |