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Semin Liver Dis 2005; 25(1): 93-104
DOI: 10.1055/s-2005-864785
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Hepatitis C Virus Particles and Lipoprotein Metabolism

Patrice André1 , Gabriel Perlemuter2 , Agata Budkowska3 , Christian Bréchot4 , Vincent Lotteau5
  • 1Professeur, INSERM, Lyon, France
  • 2INSERM Avenir, Clarmart, France
  • 3Chef de laboratoire, Unité des Hepacivirus, Institut Pasteur, Paris, France
  • 4Professeur, Unité Mixte Pasteur/INSERM, Faculté de Médecine Necker Enfants malades, Paris, France
  • 5Directeur de Recherche, INSERM, Lyon, France
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Publication History

Publication Date:
25 February 2005 (online)

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ABSTRACT

The majority of infectious hepatitis C particles are present in the low-density fractions from plasma of infected patients, suggesting an association of the virus with lipoproteins and the use of lipoprotein receptors for cell entry. Although classical hepatitis C virus (HCV) virions have been reported by some investigators, their role in the HCV life cycle has not been clearly identified. Moreover, two other forms of particles have been characterized: low-density lipo-viro-particles (LVPs) and high-density particles. The latter are nonenveloped nucleocapsids that have immunoglobulin G Fcγ binding capacity. LVPs are spherical particles enriched in triglycerides. At a minimum, they contain apolipoprotein B, HCV RNA, and core protein. The main source of LVPs is likely to be the enterocytes rather than the hepatocytes, suggesting an interaction between chylomicron and LVP assembly. In experimental systems, HCV core protein inhibits the microsomal triglyceride transfer protein, binds to apolipoprotein AII, and induces accumulation of cytoplasmic lipid droplets. A model of LVP and HCV core-lipid droplet generation is proposed.

KEYWORDS

HCV - lipoprotein - lipo-viro-particle - steatosis

REFERENCES

1 Surface Plasmon Resonance (SPR; Biacore; Biacore International, Neuchatel, Switzerland) is a biosensor-based system for real-time analysis of biospecific interactions. Biosensor technology is based on the optical SPR and detects small changes in the refraction index on the surface of a gold film coated with a dextran matrix. One reactant is covalently linked to the matrix, while another one is introduced into flow passing by over the surface. The resonance angle, expressed in resonance units (Rus), depends on the refraction index in the vicinity of the surface. It changes as the concentration of molecules on the surface changes.

  • 1 Hoofnagle J H. Course and outcome of hepatitis C.  Hepatology. 2002;  36 S21-S29
    CrossrefPubMedSearch in Google Scholar
  • 2 Pawlotsky J M. Pathophysiology of hepatitis C virus infection and related liver disease.  Trends Microbiol. 2004;  12 96-102
    CrossrefPubMedSearch in Google Scholar
  • 3 Penin F, Dubuisson J, Rey F A, Moradpour D, Pawlotsky J M. Structural biology of hepatitis C virus.  Hepatology. 2004;  39 5-19
    CrossrefPubMedSearch in Google Scholar
  • 4 Pringle C R. Virus taxonomy-1999. The universal system of virus taxonomy, updated to include the new proposals ratified by the International Committee on Taxonomy of Viruses during 1998.  Arch Virol. 1999;  144 421-429
    CrossrefPubMedSearch in Google Scholar
  • 5 Rice C M. Flaviviridae: the viruses and their replication. In: Fields BN, Knipe DM, Howley PM, et al Fields Virology, 3rd ed., Vol. 1 Philadelphia; Lippincott-Raven 1996: 931-959
    Search in Google Scholar
  • 6 Stiasny K, Bressanelli S, Lepault J, Rey F A, Heinz F X. Characterization of a membrane-associated trimeric low-pH-induced Form of the class II viral fusion protein E from tick-borne encephalitis virus and its crystallization.  J Virol. 2004;  78 3178-3183
    CrossrefPubMedSearch in Google Scholar
  • 7 Rey F A. Dengue virus envelope glycoprotein structure: new insight into its interactions during viral entry.  Proc Natl Acad Sci USA. 2003;  100 6899-6901
    CrossrefPubMedSearch in Google Scholar
  • 8 Agnello V, Abel G, Elfahal M, Knight G B, Zhang Q X. Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor.  Proc Natl Acad Sci USA. 1999;  96 12766-12771
    CrossrefPubMedSearch in Google Scholar
  • 9 Andre P, Komurian-Pradel F, Deforges S et al.. Characterization of low- and very-low-density hepatitis C virus RNA-containing particles.  J Virol. 2002;  76 6919-6928
    CrossrefPubMedSearch in Google Scholar
  • 10 Thomssen R, Bonk S, Propfe C, Heermann K H, Kochel H G, Uy A. Association of hepatitis C virus in human sera with beta-lipoprotein.  Med Microbiol Immunol (Berl). 1992;  181 293-300
    CrossrefPubMedSearch in Google Scholar
  • 11 Miyamoto H, Okamoto H, Sato K, Tanaka T, Mishiro S. Extraordinarily low density of hepatitis C virus estimated by sucrose density gradient centrifugation and the polymerase chain reaction.  J Gen Virol. 1992;  73 715-718
    PubMedSearch in Google Scholar
  • 12 Kanto T, Hayashi N, Takehara T et al.. Buoyant density of hepatitis C virus recovered from infected hosts: two different features in sucrose equilibrium density-gradient centrifugation related to degree of liver inflammation.  Hepatology. 1994;  19 296-302
    CrossrefPubMedSearch in Google Scholar
  • 13 Carrick R J, Schlauder G G, Peterson D A, Mushahwar I K. Examination of the buoyant density of hepatitis C virus by the polymerase chain reaction.  J Virol Methods. 1992;  39 279-289
    CrossrefPubMedSearch in Google Scholar
  • 14 Choo S H, So H S, Cho J M, Ryu W S. Association of hepatitis C virus particles with immunoglobulin: a mechanism for persistent infection.  J Gen Virol. 1995;  76 2337-2341
    PubMedSearch in Google Scholar
  • 15 Hijikata M, Shimizu Y K, Kato H et al.. Equilibrium centrifugation studies of hepatitis C virus: evidence for circulating immune complexes.  J Virol. 1993;  67 1953-1958
    PubMedSearch in Google Scholar
  • 16 Kanto T, Hayashi N, Takehara T et al.. Serial density analysis of hepatitis C virus particle populations in chronic hepatitis C patients treated with interferon-alpha.  J Med Virol. 1995;  46 230-237
    PubMedSearch in Google Scholar
  • 17 Pumeechockchai W, Bevitt D, Agarwal K et al.. Hepatitis C virus particles of different density in the blood of chronically infected immunocompetent and immunodeficient patients: implications for virus clearance by antibody.  J Med Virol. 2002;  68 335-342
    CrossrefPubMedSearch in Google Scholar
  • 18 Fujita N, Kaito M, Ishida S et al.. Paraformaldehyde protects of hepatitis C virus particles during ultracentrifugation.  J Med Virol. 2001;  63 108-116
    CrossrefPubMedSearch in Google Scholar
  • 19 Kaito M, Watanabe S, Tsukiyama-Kohara K et al.. Hepatitis C virus particle detected by immunoelectron microscopic study.  J Gen Virol. 1994;  75 1755-1760
    PubMedSearch in Google Scholar
  • 20 Takahashi K, Kishimoto S, Yoshizawa H, Okamoto H, Yoshikawa A, Mishiro S. p26 protein and 33-nm particle associated with nucleocapsid of hepatitis C virus recovered from the circulation of infected hosts.  Virology. 1992;  191 431-434
    CrossrefPubMedSearch in Google Scholar
  • 21 Prince A M, Huima-Byron T, Parker T S, Levine D M. Visualization of hepatitis C virions and putative defective interfering particles isolated from low-density lipoproteins.  J Viral Hepat. 1996;  3 11-17
    PubMedSearch in Google Scholar
  • 22 Ishida S, Kaito M, Kohara M et al.. Hepatitis C virus core particle detected by immunoelectron microscopy and optical rotation technique.  Hepatol Res. 2001;  20 335-347
    PubMedSearch in Google Scholar
  • 23 Kanto T, Hayashi N, Takehara T et al.. Density analysis of hepatitis C virus particle population in the circulation of infected hosts: implications for virus neutralization or persistence.  J Hepatol. 1995;  22 440-448
    CrossrefPubMedSearch in Google Scholar
  • 24 Masalova O V, Atanadze S N, Samokhvalov E I et al.. Detection of hepatitis C virus core protein circulating within different virus particle populations.  J Med Virol. 1998;  55 1-6
    CrossrefPubMedSearch in Google Scholar
  • 25 Trestard A, Bacq Y, Buzelay L et al.. Ultrastructural and physicochemical characterization of the hepatitis C virus recovered from the serum of an agammaglobulinemic patient.  Arch Virol. 1998;  143 2241-2245
    CrossrefPubMedSearch in Google Scholar
  • 26 Maillard P, Krawczynski K, Nitkiewicz J et al.. Nonenveloped nucleocapsids of hepatitis C virus in the serum of infected patients.  J Virol. 2001;  75 8240-8250
    CrossrefPubMedSearch in Google Scholar
  • 27 Okada K, Takishita Y, Shimomura H et al.. Detection of hepatitis C virus core protein in the glomeruli of patients with membranous glomerulonephritis.  Clin Nephrol. 1996;  45 71-76
    PubMedSearch in Google Scholar
  • 28 Shrivastava A, Manna S K, Ray R, Aggarwal B B. Ectopic expression of hepatitis C virus core protein differentially regulates nuclear transcription factors.  J Virol. 1998;  72 9722-9728
    PubMedSearch in Google Scholar
  • 29 Barba G, Harper F, Harada T et al.. Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets.  Proc Natl Acad Sci USA. 1997;  94 1200-1205
    CrossrefPubMedSearch in Google Scholar
  • 30 Zhu N, Khoshnan A, Schneider R et al.. Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis.  J Virol. 1998;  72 3691-3697
    PubMedSearch in Google Scholar
  • 31 Matsumoto M, Hsieh T Y, Zhu N et al.. Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-beta receptor.  J Virol. 1997;  71 1301-1309
    PubMedSearch in Google Scholar
  • 32 Jin D Y, Wang H L, Zhou Y et al.. Hepatitis C virus core protein-induced loss of LZIP function correlates with cellular transformation.  EMBO J. 2000;  19 729-740
    CrossrefPubMedSearch in Google Scholar
  • 33 Maillard P, Lavergne J P, Siberil S et al.. Fcgamma receptor-like activity of hepatitis C virus core protein.  J Biol Chem. 2004;  279 2430-2437
    PubMedSearch in Google Scholar
  • 34 Frank I, Friedman H M. A novel function of the herpes simplex virus type 1 Fc receptor: participation in bipolar bridging of antiviral immunoglobulin G.  J Virol. 1989;  63 4479-4488
    PubMedSearch in Google Scholar
  • 35 Van de Walle G R, Favoreel H W, Nauwynck H J, Pensaert M B. Antibody-induced internalization of viral glycoproteins and gE-gI Fc receptor activity protect pseudorabies virus-infected monocytes from efficient complement-mediated lysis.  J Gen Virol. 2003;  84 939-948
    CrossrefPubMedSearch in Google Scholar
  • 36 Ghetie V, Ward E S. Multiple roles for the major histocompatibility complex class I- related receptor FcRn.  Annu Rev Immunol. 2000;  18 739-766
    CrossrefPubMedSearch in Google Scholar
  • 37 Blumberg R S, Koss T, Story C M et al.. A major histocompatibility complex class I-related Fc receptor for IgG on rat hepatocytes.  J Clin Invest. 1995;  95 2397-2402
    PubMedSearch in Google Scholar
  • 38 Schilling R, Ijaz S, Davidoff M et al.. Endocytosis of hepatitis B immune globulin into hepatocytes inhibits the secretion of hepatitis B virus surface antigen and virions.  J Virol. 2003;  77 8882-8892
    CrossrefPubMedSearch in Google Scholar
  • 39 Zhu X, Meng G, Dickinson B L et al.. MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells.  J Immunol. 2001;  166 3266-3276
    PubMedSearch in Google Scholar
  • 40 Antonsson A, Johansson P J. Binding of human and animal immunoglobulins to the IgG Fc receptor induced by human cytomegalovirus.  J Gen Virol. 2001;  82 1137-1145
    PubMedSearch in Google Scholar
  • 41 Olson J K, Grose C. Endocytosis and recycling of varicella-zoster virus Fc receptor glycoprotein gE: internalization mediated by a YXXL motif in the cytoplasmic tail.  J Virol. 1997;  71 4042-4054
    PubMedSearch in Google Scholar
  • 42 Thale R, Lucin P, Schneider K, Eggers M, Koszinowski U H. Identification and expression of a murine cytomegalovirus early gene coding for an Fc receptor.  J Virol. 1994;  68 7757-7765
    PubMedSearch in Google Scholar
  • 43 Bradley D, McCaustland K, Krawczynski K, Spelbring J, Humphrey C, Cook E H. Hepatitis C virus: buoyant density of the factor VIII-derived isolate in sucrose.  J Med Virol. 1991;  34 206-208
    PubMedSearch in Google Scholar
  • 44 Shimizu Y K, Purcell R H, Yoshikura H. Correlation between the infectivity of hepatitis C virus in vivo and its infectivity in vitro.  Proc Natl Acad Sci USA. 1993;  90 6037-6041
    PubMedSearch in Google Scholar
  • 45 Thomssen R, Bonk S, Thiele A. Density heterogeneities of hepatitis C virus in human sera due to the binding of beta-lipoproteins and immunoglobulins.  Med Microbiol Immunol (Berl). 1993;  182 329-334
    PubMedSearch in Google Scholar
  • 46 Monazahian M, Kippenberger S, Muller A et al.. Binding of human lipoproteins (low, very low, high density lipoproteins) to recombinant envelope proteins of hepatitis C virus.  Med Microbiol Immunol (Berl). 2000;  188 177-184
    CrossrefPubMedSearch in Google Scholar
  • 47 Fisher E A, Ginsberg H N. Complexity in the secretory pathway: the assembly and secretion of apolipoprotein B-containing lipoproteins.  J Biol Chem. 2002;  277 17377-17380
    CrossrefPubMedSearch in Google Scholar
  • 48 Rustaeus S, Lindberg K, Stillemark P et al.. Assembly of very low density lipoprotein: a two-step process of apolipoprotein B core lipidation.  J Nutr. 1999;  129 463S-466S
    PubMedSearch in Google Scholar
  • 49 Hussain M M, Kancha R K, Zhou Z, Luchoomun J, Zu H, Bakillah A. Chylomicron assembly and catabolism: role of apolipoproteins and receptors.  Biochim Biophys Acta. 1996;  1300 151-170
    PubMedSearch in Google Scholar
  • 50 Yu K C, Cooper A D. Postprandial lipoproteins and atherosclerosis.  Front Biosci. 2001;  6 D332-D354
    CrossrefPubMedSearch in Google Scholar
  • 51 Deforges S, Evlashev A, Perret M et al.. Expression of hepatitis C virus proteins in epithelial intestinal cells in vivo.  J Gen Virol. 2004;  85 2015-2023
    CrossrefPubMedSearch in Google Scholar
  • 52 Yan F M, Chen A S, Hao F et al.. Hepatitis C virus may infect extrahepatic tissues in patients with hepatitis C.  World J Gastroenterol. 2000;  6 805-811
    PubMedSearch in Google Scholar
  • 53 Laskus T, Radkowski M, Wang L F, Jang S J, Vargas H, Rakela J. Hepatitis C virus quasispecies in patients infected with HIV-1: correlation with extrahepatic viral replication.  Virology. 1998;  248 164-171
    CrossrefPubMedSearch in Google Scholar
  • 54 Bain C, Fatmi A, Zoulim F, Zarski J P, Trepo C, Inchauspe G. Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection.  Gastroenterology. 2001;  120 512-524
    PubMedSearch in Google Scholar
  • 55 Lanford R E, Chavez D, Chisari F V, Sureau C. Lack of detection of negative-strand hepatitis C virus RNA in peripheral blood mononuclear cells and other extrahepatic tissues by the highly strand-specific rTth reverse transcriptase PCR.  J Virol. 1995;  69 8079-8083
    PubMedSearch in Google Scholar
  • 56 Laskus T, Radkowski M, Wang L F, Cianciara J, Vargas H, Rakela J. Hepatitis C virus negative strand RNA is not detected in peripheral blood mononuclear cells and viral sequences are identical to those in serum: a case against extrahepatic replication.  J Gen Virol. 1997;  78 2747-2750
    PubMedSearch in Google Scholar
  • 57 Laskus T, Radkowski M, Wang L F, Nowicki M, Rakela J. Uneven distribution of hepatitis C virus quasispecies in tissues from subjects with end-stage liver disease: confounding effect of viral adsorption and mounting evidence for the presence of low-level extrahepatic replication.  J Virol. 2000;  74 1014-1017
    CrossrefPubMedSearch in Google Scholar
  • 58 Cabot B, Martell M, Esteban J I et al.. Longitudinal evaluation of the structure of replicating and circulating hepatitis C virus quasispecies in nonprogressive chronic hepatitis C patients.  J Virol. 2001;  75 12005-12013
    CrossrefPubMedSearch in Google Scholar
  • 59 Maggi F, Fornai C, Vatteroni M L et al.. Differences in hepatitis C virus quasispecies composition between liver, peripheral blood mononuclear cells and plasma.  J Gen Virol. 1997;  78 1521-1525
    PubMedSearch in Google Scholar
  • 60 Roque Afonso A M, Jiang J, Penin F et al.. Nonrandom distribution of hepatitis C virus quasispecies in plasma and peripheral blood mononuclear cell subsets.  J Virol. 1999;  73 9213-9221
    PubMedSearch in Google Scholar
  • 61 Levy E, Beaulieu J F, Delvin E et al.. Human crypt intestinal epithelial cells are capable of lipid production, apolipoprotein synthesis, and lipoprotein assembly.  J Lipid Res. 2000;  41 12-22
    PubMedSearch in Google Scholar
  • 62 Patterson A P, Chen Z, Rubin D C et al.. Developmental regulation of apolipoprotein B mRNA editing is an autonomous function of small intestine involving homeobox gene Cdx1.  J Biol Chem. 2003;  278 7600-7606
    CrossrefPubMedSearch in Google Scholar
  • 63 Petit J M, Benichou M, Duvillard L et al.. Hepatitis C virus-associated hypobetalipoproteinemia is correlated with plasma viral load, steatosis, and liver fibrosis.  Am J Gastroenterol. 2003;  98 1150-1154
    PubMedSearch in Google Scholar
  • 64 Pileri P, Uematsu Y, Campagnoli S et al.. Binding of hepatitis C virus to CD81.  Science. 1998;  282 938-941
    CrossrefPubMedSearch in Google Scholar
  • 65 Scarselli E, Ansuini H, Cerino R et al.. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus.  EMBO J. 2002;  21 5017-5025
    CrossrefPubMedSearch in Google Scholar
  • 66 Okochi H, Mine T, Nashiro K, Suzuki J, Fujita T, Furue M. Expression of tetraspans transmembrane family in the epithelium of the gastrointestinal tract.  J Clin Gastroenterol. 1999;  29 63-67
    CrossrefPubMedSearch in Google Scholar
  • 67 Altmann S W, Davis Jr H R, Yao X et al.. The identification of intestinal scavenger receptor class B, type I (SR-BI) by expression cloning and its role in cholesterol absorption.  Biochim Biophys Acta. 2002;  1580 77-93
    PubMedSearch in Google Scholar
  • 68 Cai S F, Kirby R J, Howles P N, Hui D Y. Differentiation-dependent expression and localization of the class B type I scavenger receptor in intestine.  J Lipid Res. 2001;  42 902-909
    PubMedSearch in Google Scholar
  • 69 Out R, Kruijt J K, Rensen P C et al.. Scavenger receptor BI plays a role in facilitating chylomicron metabolism.  J Biol Chem. 2004;  279 18401-18406
    CrossrefPubMedSearch in Google Scholar
  • 70 Hope R G, McLauchlan J. Sequence motifs required for lipid droplet association and protein stability are unique to the hepatitis C virus core protein.  J Gen Virol. 2000;  81 1913-1925
    PubMedSearch in Google Scholar
  • 71 Pietschmann T, Lohmann V, Kaul A et al.. Persistent and transient replication of full-length hepatitis C virus genomes in cell culture.  J Virol. 2002;  76 4008-4021
    CrossrefPubMedSearch in Google Scholar
  • 72 Shi S T, Polyak S J, Tu H, Taylor D R, Gretch D R, Lai M M. Hepatitis C virus NS5A colocalizes with the core protein on lipid droplets and interacts with apolipoproteins.  Virology. 2002;  292 198-210
    CrossrefPubMedSearch in Google Scholar
  • 73 Lerat H, Honda M, Beard M R et al.. Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus.  Gastroenterology. 2002;  122 352-365
    CrossrefPubMedSearch in Google Scholar
  • 74 Moriya K, Yotsuyanagi H, Shintani Y et al.. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice.  J Gen Virol. 1997;  78 1527-1531
    PubMedSearch in Google Scholar
  • 75 Czaja A J, Carpenter H A, Santrach P J, Moore S B. Host- and disease-specific factors affecting steatosis in chronic hepatitis C.  J Hepatol. 1998;  29 198-206
    CrossrefPubMedSearch in Google Scholar
  • 76 Goodman Z D, Ishak K G. Histopathology of hepatitis C virus infection.  Semin Liver Dis. 1995;  15 70-81
    PubMedSearch in Google Scholar
  • 77 Serfaty L, Andreani T, Giral P, Carbonell N, Chazouilleres O, Poupon R. Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C.  J Hepatol. 2001;  34 428-434
    CrossrefPubMedSearch in Google Scholar
  • 78 Hope R G, Murphy D J, McLauchlan J. The domains required to direct core proteins of hepatitis C virus and GB virus-B to lipid droplets share common features with plant oleosin proteins.  J Biol Chem. 2002;  277 4261-4270
    CrossrefPubMedSearch in Google Scholar
  • 79 McLauchlan J, Lemberg M K, Hope G, Martoglio B. Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets.  EMBO J. 2002;  21 3980-3988
    CrossrefPubMedSearch in Google Scholar
  • 80 Sabile A, Perlemuter G, Bono F et al.. Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates.  Hepatology. 1999;  30 1064-1076
    CrossrefPubMedSearch in Google Scholar
  • 81 Perlemuter G, Sabile A, Letteron P et al.. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis.  FASEB J. 2002;  16 185-194
    CrossrefPubMedSearch in Google Scholar
  • 82 Gordon D A. Recent advances in elucidating the role of the microsomal triglyceride transfer protein in apolipoprotein B lipoprotein assembly.  Curr Opin Lipidol. 1997;  8 131-137
    PubMedSearch in Google Scholar
  • 83 Raabe M, Veniant M M, Sullivan M A et al.. Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice.  J Clin Invest. 1999;  103 1287-1298
    CrossrefPubMedSearch in Google Scholar
  • 84 Cocquerel L, Op de Beeck A, Lambot M et al.. Topological changes in the transmembrane domains of hepatitis C virus envelope glycoproteins.  EMBO J. 2002;  21 2893-2902
    CrossrefPubMedSearch in Google Scholar
  • 85 Cocquerel L, Meunier J C, Pillez A, Wychowski C, Dubuisson J. A retention signal necessary and sufficient for endoplasmic reticulum localization maps to the transmembrane domain of hepatitis C virus glycoprotein E2.  J Virol. 1998;  72 2183-2191
    PubMedSearch in Google Scholar
  • 86 Flint M, Maidens C, Loomis-Price L D et al.. Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81.  J Virol. 1999;  73 6235-6244
    PubMedSearch in Google Scholar
  • 87 Lambot M, Fretier S, Op De Beeck A et al.. Reconstitution of hepatitis C virus envelope glycoproteins into liposomes as a surrogate model to study virus attachment.  J Biol Chem. 2002;  277 20625-20630
    CrossrefPubMedSearch in Google Scholar
  • 88 Wellnitz S, Klumpp B, Barth H et al.. Binding of hepatitis C virus-like particles derived from infectious clone H77C to defined human cell lines.  J Virol. 2002;  76 1181-1193
    PubMedSearch in Google Scholar
  • 89 Clayton R F, Owsianka A, Aitken J, Graham S, Bhella D, Patel A H. Analysis of antigenicity and topology of E2 glycoprotein present on recombinant hepatitis C virus-like particles.  J Virol. 2002;  76 7672-7682
    CrossrefPubMedSearch in Google Scholar
  • 90 Pohlmann S, Zhang J, Baribaud F et al.. Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR.  J Virol. 2003;  77 4070-4080
    CrossrefPubMedSearch in Google Scholar
  • 91 Lozach P Y, Lortat-Jacob H, de Lacroix-de Lavalette A et al.. DC-SIGN and L-SIGN are high affinity binding receptors for hepatitis C virus glycoprotein E2.  J Biol Chem. 2003;  278 20358-20366
    CrossrefPubMedSearch in Google Scholar
  • 92 Lagging L M, Meyer K, Owens R J, Ray R. Functional role of hepatitis C virus chimeric glycoproteins in the infectivity of pseudotyped virus.  J Virol. 1998;  72 3539-3546
    PubMedSearch in Google Scholar
  • 93 Matsuura Y, Tani H, Suzuki K et al.. Characterization of pseudotype VSV possessing HCV envelope proteins.  Virology. 2001;  286 263-275
    CrossrefPubMedSearch in Google Scholar
  • 94 Buonocore L, Blight K J, Rice C M, Rose J K. Characterization of vesicular stomatitis virus recombinants that express and incorporate high levels of hepatitis C virus glycoproteins.  J Virol. 2002;  76 6865-6872
    CrossrefPubMedSearch in Google Scholar
  • 95 Bartosch B, Dubuisson J, Cosset F L. Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes.  J Exp Med. 2003;  197 633-642
    CrossrefPubMedSearch in Google Scholar
  • 96 Hsu M, Zhang J, Flint M et al.. Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles.  Proc Natl Acad Sci USA. 2003;  100 7271-7276
    CrossrefPubMedSearch in Google Scholar
  • 97 Bartosch B, Vitelli A, Granier C et al.. Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor.  J Biol Chem. 2003;  278 41624-41630
    CrossrefPubMedSearch in Google Scholar
  • 98 Forns X, Thimme R, Govindarajan S et al.. Hepatitis C virus lacking the hypervariable region 1 of the second envelope protein is infectious and causes acute resolving or persistent infection in chimpanzees.  Proc Natl Acad Sci USA. 2000;  97 13318-13323
    CrossrefPubMedSearch in Google Scholar
  • 99 Murphy D J, Vance J. Mechanisms of lipid-body formation.  Trends Biochem Sci. 1999;  24 109-115
    CrossrefPubMedSearch in Google Scholar
  • 100 Konan K V, Giddings Jr T H, Ikeda M, Li K, Lemon S M, Kirkegaard K. Nonstructural protein precursor NS4A/B from hepatitis C virus alters function and ultrastructure of host secretory apparatus.  J Virol. 2003;  77 7843-7855
    CrossrefPubMedSearch in Google Scholar
  • 101 Moradpour D, Gosert R, Egger D, Penin F, Blum H E, Bienz K. Membrane association of hepatitis C virus nonstructural proteins and identification of the membrane alteration that harbors the viral replication complex.  Antiviral Res. 2003;  60 103-109
    CrossrefPubMedSearch in Google Scholar
  • 102 Miura S, Gan J W, Brzostowski J et al.. Functional conservation for lipid storage droplet association among Perilipin, ADRP, and TIP47 (PAT)-related proteins in mammals, Drosophila, and Dictyostelium.  J Biol Chem. 2002;  277 32253-32257
    CrossrefPubMedSearch in Google Scholar
  • 103 Targett-Adams P, Chambers D, Gledhill S et al.. Live cell analysis and targeting of the lipid droplet-binding adipocyte differentiation-related protein.  J Biol Chem. 2003;  278 15998-16007
    CrossrefPubMedSearch in Google Scholar
  • 104 Imamura M, Inoguchi T, Ikuyama S et al.. ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts.  Am J Physiol Endocrinol Metab. 2002;  283 E775-E783
    PubMedSearch in Google Scholar
  • 105 Caldas H, Herman G E. NSDHL, an enzyme involved in cholesterol biosynthesis, traffics through the Golgi and accumulates on ER membranes and on the surface of lipid droplets.  Hum Mol Genet. 2003;  12 2981-2991
    CrossrefPubMedSearch in Google Scholar
  • 106 van Meer G. Caveolin, cholesterol, and lipid droplets?.  J Cell Biol. 2001;  152 F29-34
    CrossrefPubMedSearch in Google Scholar

Patrice AndréM.D. 

Professeur, INSERM U503, IFR 128 Biosciences Lyon Gerland

21 avenue Tony Garnier, 69365 Lyon cedex 07, France

Email: andre@cervi-lyon.inserm.fr