更新于：2024-11-01

HCV E1 x HCV E2

更新于：2024-11-01

基本信息

关联

项与 HCV E1 x HCV E2 相关的药物

Hepatitis C virus glycoprotein nanoparticle vaccine(Universiteit van Amsterdam)

丙型病毒性肝炎纳米颗粒疫苗(阿姆斯特丹大学)

靶点

HCV E1 x HCV E2

作用机制

HCV E1抑制剂 [+1]

在研机构

University of Amsterdam

原研机构

University of Amsterdam

在研适应症

病毒性肝炎

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 HCV E1 x HCV E2 相关的临床结果

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100 项与 HCV E1 x HCV E2 相关的转化医学

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0 项与 HCV E1 x HCV E2 相关的专利（医药）

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项与 HCV E1 x HCV E2 相关的文献（医药）

2006-07-01·Journal of Biological Chemistry2区 · 生物学

High Density Lipoprotein Inhibits Hepatitis C Virus-neutralizing Antibodies by Stimulating Cell Entry via Activation of the Scavenger Receptor BI

2区 · 生物学

Article

作者: Philippe-Emmanuel Mangeot ; Thomas Pietschmann ; Zhenyong Keck ; Dimitri Lavillette ; Christelle Granier ; Marlène Dreux ; Francois-Loïc Cosset ; Cécile Voisset ; Ralf Bartenschlager ; Sylvie Ricard-Blum ; Ngoc Vu-Dac ; Steven Foung ; Jean Dubuisson

Hepatitis C virus (HCV) exploits serum-dependent mechanisms that inhibit neutralizing antibodies. Here we demonstrate that high density lipoprotein (HDL) is a key serum factor that attenuates neutralization by monoclonal and HCV patient-derived polyclonal antibodies of infectious pseudo-particles (HCVpp) harboring authentic E1E2 glycoproteins and cell culture-grown genuine HCV (HCVcc). Over 10-fold higher antibody concentrations are required to neutralize either HCV-enveloped particles in the presence of HDL or human serum, and less than 3-5-fold reduction of infectious titers are obtained at saturating antibody concentrations, in contrast to complete inhibition in serum-free conditions. We show that HDL interaction with the scavenger receptor BI (SR-BI), a proposed cell entry co-factor of HCV and a receptor mediating lipid transfer with HDL, strongly reduces neutralization of HCVpp and HCVcc. We found that HDL activation of target cells strongly stimulates cell entry of viral particles by accelerating their endocytosis, thereby suppressing a 1-h time lag during which cell-bound virions are not internalized and can be targeted by antibodies. Compounds that inhibit lipid transfer functions of SR-BI fully restore neutralization by antibodies in human serum. We demonstrate that this functional HDL/SR-BI interaction only interferes with antibodies blocking HCV-E2 binding to CD81, a major HCV receptor, reflecting its prominent role during the cell entry process. Moreover, we identify monoclonal antibodies targeted to epitopes in the E1E2 complex that are not inhibited by HDL. Consistently, we show that antibodies targeted to HCV-E1 efficiently neutralize HCVpp and HCVcc in the presence of human serum.

2003-11-01·Journal of Biological Chemistry2区 · 生物学

Mapping of a Conformational Epitope Shared between E1 and E2 on the Serum-derived Human Hepatitis C Virus Envelope

2区 · 生物学

Article

作者: Yvonne Michal ; Colette Jolivet-Reynaud ; Christian Trépo ; Marie-Anne Petit ; Estelle Peronnet

Monoclonal antibody D32.10 produced by immunizing mice with a hepatitis C virus (HCV)-enriched pellet obtained from plasmapheresis of a chronically HCV1b-infected patient binds HCV particles derived from serum of different HCV1a- and HCV1b-infected patients. Moreover, this monoclonal has been shown to recognize both HCV envelope proteins E1 and E2. In an attempt to provide novel insight into the membrane topology of HCV envelope glycoproteins E1 and E2, we localized the epitope recognized by D32.10 on the E1 and/or E2 sequence using Ph.D.-12 phage display peptide library technology. Mimotopes selected from the phage display dodecapeptide library by D32.10 shared partial similarities with 297RHWTTQGCNC306 of the HCV E1 glycoprotein and with both 613YRLWHYPCT621 and 480PDQRPYCWHYPPKPC494 of the HCV E2 glycoprotein. Immunoreactivity of D32.10 with overlapping peptides corresponding to these three HCV regions confirmed these localizations and suggested that the three regions identified are likely closely juxtaposed on the surface of serum-derived particles as predicted by the secondary model structure of HCV E2 derived from the tick-borne encephalitis virus E protein. This assertion was supported by the detection of specific antibodies directed against these three E1E2 regions in sera from HCV-infected patients.

International Journal of Molecular Medicine3区 · 医学

Morphological identification of hepatitis C virus E1 and E2 envelope glycoproteins on the virion surface using immunogold electron microscopy

3区 · 医学

Article

作者: Fujita, Naoki ; Tanaka, Hideaki ; Watanabe, Shozo ; Gabazza, Esteban Cesar ; Adachi, Yukihiko ; Tsukiyama-Kohara, Kyoko ; Kohara, Michinori ; Iwasa, Motoh ; Kaito, Masahiko ; Kobayashi, Yoshinao ; Konishi, Masayoshi

It is known that hepatitis C virus (HCV) particles are spherical, 55-65 nm particles with fine surface projections of about 6 nm in length and with a 30-35 nm inner core. We have reported that free HCV particles labeled with gold particles specific to the HCV E1 glycoprotein are located in 1.14-1.16 g/ml fractions from plasma samples with high HCV RNA titers after sucrose density gradient centrifugation. However, the morphology of the HCV E2 glycoprotein on the virion has not yet been elucidated. To visualize HCV E2 localization on the virion, we used the same plasma samples where HCV particles were clearly shown. An indirect immunogold electron microscopic study was carried out using monoclonal and polyclonal anti-HCV E2 antibodies. HCV-like particles specifically reacted with the anti-HCV E2 antibodies. Moreover, to evaluate the localization of the HCV E1 and E2 glycoproteins on the virion surface, an immunogold electron microscopic study using double labeling with anti-HCV E1 antibodies and anti-HCV E2 antibodies was also performed. These particles also specifically reacted with both anti-E1 and E2 antibodies. This is the first report showing the presence of both HCV E1 and E2 glycoproteins on HCV virion surface in human plasma samples.