This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Petracca, R.
Right arrow Articles by Grandi, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Petracca, R.
Right arrow Articles by Grandi, G.

 Previous Article  |  Next Article 

Journal of Virology, May 2000, p. 4824-4830, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Structure-Function Analysis of Hepatitis C Virus Envelope-CD81 Binding

Roberto Petracca,1 Fabiana Falugi,1 Giuliano Galli,1 Nathalie Norais,1 Domenico Rosa,1 Susanna Campagnoli,1 Vito Burgio,2 Enrico Di Stasio,3 Bruno Giardina,4 Michael Houghton,5 Sergio Abrignani,1 and Guido Grandi1,*

Chiron Research Centre, 53100 Siena,1 Fondazione Andrea Cesalpino, c/o Istituto I Clinica Medica, Università La Sapienza, Policlinico Umberto I, 00161 Rome,2 and Istituto di Fisica3 and Istituto di Chimica e Chimica Clinica,4 Facoltà di Medicina e Chirurgia, UCSC, 00168 Rome, Italy, and Chiron Technologies, Emeryville, California 946085

Received 30 November 1999/Accepted 10 February 2000

Hepatitis C virus (HCV) is a major human pathogen causing chronic liver disease. We have recently found that the large extracellular loop (LEL) of human CD81 binds HCV. This finding prompted us to assess the structure-function features of HCV-CD81 interaction by using recombinant E2 protein and a recombinant soluble form of CD81 LEL. We have found that HCV-E2 binds CD81 LEL with a Kd of 1.8 nM; CD81 can mediate attachment of E2 on hepatocytes; engagement of CD81 mediates internalization of only 30% of CD81 molecules even after 12 h; and the four cysteines of CD81 LEL form two disulfide bridges, the integrity of which is necessary for CD81-HCV interaction. Altogether our data suggest that neutralizing antibodies aimed at interfering with HCV binding to human cells should have an affinity higher than 10-9 M, that HCV binding to hepatocytes may not entirely depend on CD81, that CD81 is an attachment receptor with poor capacity to mediate virus entry, and that reducing environments do not favor CD81-HCV interaction. These studies provide a better understanding of the CD81-HCV interaction and should thus help to elucidate the viral life cycle and to develop new strategies aimed at interfering with HCV binding to human cells.

* Corresponding author. Mailing address: Chiron Research Centre, Via Fiorentina 1, 53100 Siena, Italy. Phone: 39-0577-243506. Fax: 39-0577-243564. E-mail: guido_grandi{at}biocine.it.

Journal of Virology, May 2000, p. 4824-4830, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Machida, K., Kondo, Y., Huang, J. Y., Chen, Y.-C., Cheng, K. T.-H., Keck, Z., Foung, S., Dubuisson, J., Sung, V. M.-H., Lai, M. M. C. (2008). Hepatitis C Virus (HCV)-Induced Immunoglobulin Hypermutation Reduces the Affinity and Neutralizing Activities of Antibodies against HCV Envelope Protein. J. Virol. 82: 6711-6720 [Abstract] [Full Text]  
  • Yang, W., Qiu, C., Biswas, N., Jin, J., Watkins, S. C., Montelaro, R. C., Coyne, C. B., Wang, T. (2008). Correlation of the Tight Junction-like Distribution of Claudin-1 to the Cellular Tropism of Hepatitis C Virus. J. Biol. Chem. 283: 8643-8653 [Abstract] [Full Text]  
  • Molina, S., Castet, V., Pichard-Garcia, L., Wychowski, C., Meurs, E., Pascussi, J.-M., Sureau, C., Fabre, J.-M., SaCunha, A., Larrey, D., Dubuisson, J., Coste, J., McKeating, J., Maurel, P., Fournier-Wirth, C. (2008). Serum-Derived Hepatitis C Virus Infection of Primary Human Hepatocytes Is Tetraspanin CD81 Dependent. J. Virol. 82: 569-574 [Abstract] [Full Text]  
  • Viswanatha, D S, Dogan, A (2007). Hepatitis C virus and lymphoma. J. Clin. Pathol. 60: 1378-1383 [Abstract] [Full Text]  
  • Sansonno, D., Carbone, A., De Re, V., Dammacco, F. (2007). Hepatitis C virus infection, cryoglobulinaemia, and beyond. Rheumatology (Oxford) 46: 572-578 [Abstract] [Full Text]  
  • McLinden, J. H., Kaufman, T. M., Xiang, J., Chang, Q., Klinzman, D., Engel, A. M., Hess, G., Schmidt, U., Houghton, M., Stapleton, J. T. (2006). Characterization of an Immunodominant Antigenic Site on GB Virus C Glycoprotein E2 That Is Involved in Cell Binding. J. Virol. 80: 12131-12140 [Abstract] [Full Text]  
  • Meertens, L., Bertaux, C., Dragic, T. (2006). Hepatitis C Virus Entry Requires a Critical Postinternalization Step and Delivery to Early Endosomes via Clathrin-Coated Vesicles. J. Virol. 80: 11571-11578 [Abstract] [Full Text]  
  • Flint, M., von Hahn, T., Zhang, J., Farquhar, M., Jones, C. T., Balfe, P., Rice, C. M., McKeating, J. A. (2006). Diverse CD81 Proteins Support Hepatitis C Virus Infection. J. Virol. 80: 11331-11342 [Abstract] [Full Text]  
  • Codran, A., Royer, C., Jaeck, D., Bastien-Valle, M., Baumert, T. F., Kieny, M. P., Pereira, C. A., Martin, J.-P. (2006). Entry of hepatitis C virus pseudotypes into primary human hepatocytes by clathrin-dependent endocytosis. J. Gen. Virol. 87: 2583-2593 [Abstract] [Full Text]  
  • Drummer, H. E., Boo, I., Maerz, A. L., Poumbourios, P. (2006). 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. 80: 7844-7853 [Abstract] [Full Text]  
  • Zhao, L.-J., Zhang, X.-L., Zhao, P., Cao, J., Cao, M.-M., Zhu, S.-Y., Liu, H.-Q., Qi, Z.-T. (2006). Up-regulation of ERK and p38 MAPK signaling pathways by hepatitis C virus E2 envelope protein in human T lymphoma cell line. J. Leukoc. Biol. 80: 424-432 [Abstract] [Full Text]  
  • Ho, S.-H., Martin, F., Higginbottom, A., Partridge, L. J., Parthasarathy, V., Moseley, G. W., Lopez, P., Cheng-Mayer, C., Monk, P. N. (2006). Recombinant extracellular domains of tetraspanin proteins are potent inhibitors of the infection of macrophages by human immunodeficiency virus type 1.. J. Virol. 80: 6487-6496 [Abstract] [Full Text]  
  • Cocquerel, L., Voisset, C., Dubuisson, J. (2006). Hepatitis C virus entry: potential receptors and their biological functions.. J. Gen. Virol. 87: 1075-1084 [Abstract] [Full Text]  
  • Bertaux, C., Dragic, T. (2006). Different domains of CD81 mediate distinct stages of hepatitis C virus pseudoparticle entry.. J. Virol. 80: 4940-4948 [Abstract] [Full Text]  
  • Tscherne, D. M., Jones, C. T., Evans, M. J., Lindenbach, B. D., McKeating, J. A., Rice, C. M. (2006). Time- and Temperature-Dependent Activation of Hepatitis C Virus for Low-pH-Triggered Entry. J. Virol. 80: 1734-1741 [Abstract] [Full Text]  
  • Martin, F., Roth, D. M., Jans, D. A., Pouton, C. W., Partridge, L. J., Monk, P. N., Moseley, G. W. (2005). Tetraspanins in Viral Infections: a Fundamental Role in Viral Biology?. J. Virol. 79: 10839-10851 [Full Text]  
  • Mazzocca, A., Sciammetta, S. C., Carloni, V., Cosmi, L., Annunziato, F., Harada, T., Abrignani, S., Pinzani, M. (2005). Binding of Hepatitis C Virus Envelope Protein E2 to CD81 Up-regulates Matrix Metalloproteinase-2 in Human Hepatic Stellate Cells. J. Biol. Chem. 280: 11329-11339 [Abstract] [Full Text]  
  • Tan, Y.-J., Teng, E., Shen, S., Tan, T. H. P., Goh, P.-Y., Fielding, B. C., Ooi, E.-E., Tan, H.-C., Lim, S. G., Hong, W. (2004). A Novel Severe Acute Respiratory Syndrome Coronavirus Protein, U274, Is Transported to the Cell Surface and Undergoes Endocytosis. J. Virol. 78: 6723-6734 [Abstract] [Full Text]  
  • Heo, T.-H., Chang, J.-H., Lee, J.-W., Foung, S. K. H., Dubuisson, J., Kang, C.-Y. (2004). Incomplete Humoral Immunity against Hepatitis C Virus Is Linked with Distinct Recognition of Putative Multiple Receptors by E2 Envelope Glycoprotein. J. Immunol. 173: 446-455 [Abstract] [Full Text]  
  • Cormier, E. G., Tsamis, F., Kajumo, F., Durso, R. J., Gardner, J. P., Dragic, T. (2004). CD81 is an entry coreceptor for hepatitis C virus. Proc. Natl. Acad. Sci. USA 101: 7270-7274 [Abstract] [Full Text]  
  • Clark, K. L., Oelke, A., Johnson, M. E., Eilert, K. D., Simpson, P. C., Todd, S. C. (2004). CD81 Associates with 14-3-3 in a Redox-regulated Palmitoylation-dependent Manner. J. Biol. Chem. 279: 19401-19406 [Abstract] [Full Text]  
  • Zhang, J., Randall, G., Higginbottom, A., Monk, P., Rice, C. M., McKeating, J. A. (2004). CD81 Is Required for Hepatitis C Virus Glycoprotein-Mediated Viral Infection. J. Virol. 78: 1448-1455 [Abstract] [Full Text]  
  • Ellerman, D. A., Ha, C., Primakoff, P., Myles, D. G., Dveksler, G. S. (2003). Direct Binding of the Ligand PSG17 to CD9 Requires a CD9 Site Essential for Sperm-Egg Fusion. Mol. Biol. Cell 14: 5098-5103 [Abstract] [Full Text]  
  • Bartosch, B., Vitelli, A., Granier, C., Goujon, C., Dubuisson, J., Pascale, S., Scarselli, E., Cortese, R., Nicosia, A., Cosset, F.-L. (2003). 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. 278: 41624-41630 [Abstract] [Full Text]  
  • Balasubramanian, A., Ganju, R. K., Groopman, J. E. (2003). Hepatitis C Virus and HIV Envelope Proteins Collaboratively Mediate Interleukin-8 Secretion through Activation of p38 MAP Kinase and SHP2 in Hepatocytes. J. Biol. Chem. 278: 35755-35766 [Abstract] [Full Text]  
  • Lozach, P.-Y., Lortat-Jacob, H., De Lacroix De Lavalette, A., Staropoli, I., Foung, S., Amara, A., Houles, C., Fieschi, F., Schwartz, O., Virelizier, J.-L., Arenzana-Seisdedos, F., Altmeyer, R. (2003). DC-SIGN and L-SIGN Are High Affinity Binding Receptors for Hepatitis C Virus Glycoprotein E2. J. Biol. Chem. 278: 20358-20366 [Abstract] [Full Text]  
  • Nozaki, A., Ikeda, M., Naganuma, A., Nakamura, T., Inudoh, M., Tanaka, K., Kato, N. (2003). Identification of a Lactoferrin-derived Peptide Possessing Binding Activity to Hepatitis C Virus E2 Envelope Protein. J. Biol. Chem. 278: 10162-10173 [Abstract] [Full Text]  
  • Drummer, H. E., Wilson, K. A., Poumbourios, P. (2002). Identification of the Hepatitis C Virus E2 Glycoprotein Binding Site on the Large Extracellular Loop of CD81. J. Virol. 76: 11143-11147 [Abstract] [Full Text]  
  • Triyatni, M., Saunier, B., Maruvada, P., Davis, A. R., Ulianich, L., Heller, T., Patel, A., Kohn, L. D., Liang, T. J. (2002). Interaction of Hepatitis C Virus-Like Particles and Cells: a Model System for Studying Viral Binding and Entry. J. Virol. 76: 9335-9344 [Abstract] [Full Text]  
  • Clayton, R. F., Owsianka, A., Aitken, J., Graham, S., Bhella, D., Patel, A. H. (2002). Analysis of Antigenicity and Topology of E2 Glycoprotein Present on Recombinant Hepatitis C Virus-Like Particles. J. Virol. 76: 7672-7682 [Abstract] [Full Text]  
  • Andre, P., Komurian-Pradel, F., Deforges, S., Perret, M., Berland, J. L., Sodoyer, M., Pol, S., Brechot, C., Paranhos-Baccala, G., Lotteau, V. (2002). Characterization of Low- and Very-Low-Density Hepatitis C Virus RNA-Containing Particles. J. Virol. 76: 6919-6928 [Abstract] [Full Text]  
  • Lambot, M., Fretier, S., De Beeck, A. O., Quatannens, B., Lestavel, S., Clavey, V., Dubuisson, J. (2002). Reconstitution of Hepatitis C Virus Envelope Glycoproteins into Liposomes as a Surrogate Model to Study Virus Attachment. J. Biol. Chem. 277: 20625-20630 [Abstract] [Full Text]  
  • Meyer, K., Basu, A., Przysiecki, C. T., Lagging, L. M., Di Bisceglie, A. M., Conley, A. J., Ray, R. (2002). Complement-Mediated Enhancement of Antibody Function for Neutralization of Pseudotype Virus Containing Hepatitis C Virus E2 Chimeric Glycoprotein. J. Virol. 76: 2150-2158 [Abstract] [Full Text]  
  • Wellnitz, S., Klumpp, B., Barth, H., Ito, S., Depla, E., Dubuisson, J., Blum, H. E., Baumert, T. F. (2002). Binding of Hepatitis C Virus-Like Particles Derived from Infectious Clone H77C to Defined Human Cell Lines. J. Virol. 76: 1181-1193 [Abstract] [Full Text]  
  • Quinn, E. R., Chan, C. H., Hadlock, K. G., Foung, S. K. H., Flint, M., Levy, S. (2001). The B-cell receptor of a hepatitis C virus (HCV)-associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis. Blood 98: 3745-3749 [Abstract] [Full Text]  
  • Yeh, C.-T., Lai, H.-Y., Chen, T.-C., Chu, C.-M., Liaw, Y.-F. (2001). Identification of a Hepatic Factor Capable of Supporting Hepatitis C Virus Replication in a Nonpermissive Cell Line. J. Virol. 75: 11017-11024 [Abstract] [Full Text]  
  • Clark, K. L., Zeng, Z., Langford, A. L., Bowen, S. M., Todd, S. C. (2001). PGRL Is a Major CD81-Associated Protein on Lymphocytes and Distinguishes a New Family of Cell Surface Proteins. J. Immunol. 167: 5115-5121 [Abstract] [Full Text]  
  • Cerino, A., Meola, A., Segagni, L., Furione, M., Marciano, S., Triyatni, M., Liang, T. J., Nicosia, A., Mondelli, M. U. (2001). Monoclonal Antibodies with Broad Specificity for Hepatitis C Virus Hypervariable Region 1 Variants Can Recognize Viral Particles. J. Immunol. 167: 3878-3886 [Abstract] [Full Text]  
  • Owsianka, A., Clayton, R. F., Loomis-Price, L. D., McKeating, J. A., Patel, A. H. (2001). Functional analysis of hepatitis C virus E2 glycoproteins and virus-like particles reveals structural dissimilarities between different forms of E2. J. Gen. Virol. 82: 1877-1883 [Abstract] [Full Text]  
  • Takahashi, Y., Bigler, D., Ito, Y., White, J. M. (2001). Sequence-Specific Interaction between the Disintegrin Domain of Mouse ADAM 3 and Murine Eggs: Role of {beta}1 Integrin-associated Proteins CD9, CD81, and CD98. Mol. Biol. Cell 12: 809-820 [Abstract] [Full Text]  
  • Wünschmann, S., Medh, J. D., Klinzmann, D., Schmidt, W. N., Stapleton, J. T. (2000). Characterization of Hepatitis C Virus (HCV) and HCV E2 Interactions with CD81 and the Low-Density Lipoprotein Receptor. J. Virol. 74: 10055-10062 [Abstract] [Full Text]  
  • Heile, J. M., Fong, Y.-L., Rosa, D., Berger, K., Saletti, G., Campagnoli, S., Bensi, G., Capo, S., Coates, S., Crawford, K., Dong, C., Wininger, M., Baker, G., Cousens, L., Chien, D., Ng, P., Archangel, P., Grandi, G., Houghton, M., Abrignani, S. (2000). Evaluation of Hepatitis C Virus Glycoprotein E2 for Vaccine Design: an Endoplasmic Reticulum-Retained Recombinant Protein Is Superior to Secreted Recombinant Protein and DNA-Based Vaccine Candidates. J. Virol. 74: 6885-6892 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»