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 Farzan, M.
Right arrow Articles by Sodroski, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Farzan, M.
Right arrow Articles by Sodroski, J.

 Previous Article  |  Next Article 

Journal of Virology, September 1998, p. 7620-7625, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Stabilization of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers by Disulfide Bonds Introduced into the gp41 Glycoprotein Ectodomain

Michael Farzan,1,* Hyeryun Choe,1 Elizabeth Desjardins,1 Ying Sun,1 Jens Kuhn,1 Jie Cao,1 Danielle Archambault,1 Peter Kolchinsky,1 Markus Koch,1 Richard Wyatt,1 and Joseph Sodroski1,2

Division of Human Retrovirology, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School,1 and Department of Cancer Biology, Harvard School of Public Health,2 Boston, Massachusetts 02115

Received 8 August 1997/Accepted 21 May 1998

Biochemical and structural studies of fragments of the ectodomain of the human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane envelope glycoprotein have demonstrated that the molecular contacts between alpha helices allow the formation of a trimeric coiled coil. By introducing cysteine residues into specific locations along these alpha helices, the normally labile HIV-1 gp160 envelope glycoprotein was converted into a stable disulfide-linked oligomer. Although proteolytic cleavage into gp120 and gp41 glycoproteins was largely blocked, the disulfide-linked oligomer was efficiently transported to the cell surface and was recognized by a series of conformationally dependent antibodies. The pattern of hetero-oligomer formation between this construct and an analogous construct lacking portions of the gp120 variable loops and of the gp41 cytoplasmic tail demonstrates that these oligomers are trimers. These results support the relevance of the proposed gp41 structure and intersubunit contacts to the native, complete HIV-1 envelope glycoprotein. Disulfide-mediated stabilization of the labile HIV-1 envelope glycoprotein oligomer, which has been suggested to possess advantages as an immunogen, may assist attempts to develop vaccines.

* Corresponding author. Mailing address: JFB824, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115. Phone: (617) 632-4358. Fax: (617) 632-3113. E-mail: farzan{at}mbcrr.harvard.edu.

Journal of Virology, September 1998, p. 7620-7625, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Kraft, Z., Strouss, K., Sutton, W. F., Cleveland, B., Tso, F. Y., Polacino, P., Overbaugh, J., Hu, S.-L., Stamatatos, L. (2008). Characterization of Neutralizing Antibody Responses Elicited by Clade A Envelope Immunogens Derived from Early Transmitted Viruses. J. Virol. 82: 5912-5921 [Abstract] [Full Text]  
  • Lazear, E., Carfi, A., Whitbeck, J. C., Cairns, T. M., Krummenacher, C., Cohen, G. H., Eisenberg, R. J. (2008). Engineered Disulfide Bonds in Herpes Simplex Virus Type 1 gD Separate Receptor Binding from Fusion Initiation and Viral Entry. J. Virol. 82: 700-709 [Abstract] [Full Text]  
  • Pacheco, B., Basmaciogullari, S., LaBonte, J. A., Xiang, S.-H., Sodroski, J. (2008). Adaptation of the Human Immunodeficiency Virus Type 1 Envelope Glycoproteins to New World Monkey Receptors. J. Virol. 82: 346-357 [Abstract] [Full Text]  
  • Forsell, M. N. E., McInerney, G. M., Dosenovic, P., Hidmark, A. S., Eriksson, C., Liljestrom, P., Grundner, C., Karlsson Hedestam, G. B. (2007). Increased human immunodeficiency virus type 1 Env expression and antibody induction using an enhanced alphavirus vector. J. Gen. Virol. 88: 2774-2779 [Abstract] [Full Text]  
  • Forsell, M. N. E., Li, Y., Sundback, M., Svehla, K., Liljestrom, P., Mascola, J. R., Wyatt, R., Hedestam, G. B. K. (2005). Biochemical and Immunogenic Characterization of Soluble Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers Expressed by Semliki Forest Virus. J. Virol. 79: 10902-10914 [Abstract] [Full Text]  
  • Connolly, S. A., Landsburg, D. J., Carfi, A., Whitbeck, J. C., Zuo, Y., Wiley, D. C., Cohen, G. H., Eisenberg, R. J. (2005). Potential Nectin-1 Binding Site on Herpes Simplex Virus Glycoprotein D. J. Virol. 79: 1282-1295 [Abstract] [Full Text]  
  • Yang, X., Tomov, V., Kurteva, S., Wang, L., Ren, X., Gorny, M. K., Zolla-Pazner, S., Sodroski, J. (2004). Characterization of the Outer Domain of the gp120 Glycoprotein from Human Immunodeficiency Virus Type 1. J. Virol. 78: 12975-12986 [Abstract] [Full Text]  
  • Bower, J. F., Yang, X., Sodroski, J., Ross, T. M. (2004). Elicitation of Neutralizing Antibodies with DNA Vaccines Expressing Soluble Stabilized Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers Conjugated to C3d. J. Virol. 78: 4710-4719 [Abstract] [Full Text]  
  • Vinayagam, A., Pugalenthi, G., Rajesh, R., Sowdhamini, R. (2004). DSDBASE: a consortium of native and modelled disulphide bonds in proteins. Nucleic Acids Res 32: D200-202 [Abstract] [Full Text]  
  • Nishimura, Y., Igarashi, T., Haigwood, N. L., Sadjadpour, R., Donau, O. K., Buckler, C., Plishka, R. J., Buckler-White, A., Martin, M. A. (2003). Transfer of neutralizing IgG to macaques 6 h but not 24 h after SHIV infection confers sterilizing protection: Implications for HIV-1 vaccine development. Proc. Natl. Acad. Sci. USA 100: 15131-15136 [Abstract] [Full Text]  
  • Poumbourios, P., Maerz, A. L., Drummer, H. E. (2003). Functional Evolution of the HIV-1 Envelope Glycoprotein 120 Association Site of Glycoprotein 41. J. Biol. Chem. 278: 42149-42160 [Abstract] [Full Text]  
  • Srivastava, I. K., Stamatatos, L., Kan, E., Vajdy, M., Lian, Y., Hilt, S., Martin, L., Vita, C., Zhu, P., Roux, K. H., Vojtech, L., C. Montefiori, D., Donnelly, J., Ulmer, J. B., Barnett, S. W. (2003). Purification, Characterization, and Immunogenicity of a Soluble Trimeric Envelope Protein Containing a Partial Deletion of the V2 Loop Derived from SF162, an R5-Tropic Human Immunodeficiency Virus Type 1 Isolate. J. Virol. 77: 11244-11259 [Abstract] [Full Text]  
  • Willey, R. L., Byrum, R., Piatak, M., Kim, Y. B., Cho, M. W., Rossio, J. L. Jr., Bess, J. Jr., Igarashi, T., Endo, Y., Arthur, L. O., Lifson, J. D., Martin, M. A. (2002). Control of Viremia and Prevention of Simian-Human Immunodeficiency Virus-Induced Disease in Rhesus Macaques Immunized with Recombinant Vaccinia Viruses plus Inactivated Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Particles. J. Virol. 77: 1163-1174 [Abstract] [Full Text]  
  • Sanders, R. W., Vesanen, M., Schuelke, N., Master, A., Schiffner, L., Kalyanaraman, R., Paluch, M., Berkhout, B., Maddon, P. J., Olson, W. C., Lu, M., Moore, J. P. (2002). Stabilization of the Soluble, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1. J. Virol. 76: 8875-8889 [Abstract] [Full Text]  
  • Schulke, N., Vesanen, M. S., Sanders, R. W., Zhu, P., Lu, M., Anselma, D. J., Villa, A. R., Parren, P. W. H. I., Binley, J. M., Roux, K. H., Maddon, P. J., Moore, J. P., Olson, W. C. (2002). Oligomeric and Conformational Properties of a Proteolytically Mature, Disulfide-Stabilized Human Immunodeficiency Virus Type 1 gp140 Envelope Glycoprotein. J. Virol. 76: 7760-7776 [Abstract] [Full Text]  
  • Center, R. J., Leapman, R. D., Lebowitz, J., Arthur, L. O., Earl, P. L., Moss, B. (2002). Oligomeric Structure of the Human Immunodeficiency Virus Type 1 Envelope Protein on the Virion Surface. J. Virol. 76: 7863-7867 [Abstract] [Full Text]  
  • Liu, J., Wang, S., Hoxie, J. A., LaBranche, C. C., Lu, M. (2002). Mutations That Destabilize the gp41 Core Are Determinants for Stabilizing the Simian Immunodeficiency Virus-CPmac Envelope Glycoprotein Complex. J. Biol. Chem. 277: 12891-12900 [Abstract] [Full Text]  
  • Yang, X., Lee, J., Mahony, E. M., Kwong, P. D., Wyatt, R., Sodroski, J. (2002). Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin. J. Virol. 76: 4634-4642 [Abstract] [Full Text]  
  • Puffer, B. A., Pohlmann, S., Edinger, A. L., Carlin, D., Sanchez, M. D., Reitter, J., Watry, D. D., Fox, H. S., Desrosiers, R. C., Doms, R. W. (2002). CD4 Independence of Simian Immunodeficiency Virus Envs Is Associated with Macrophage Tropism, Neutralization Sensitivity, and Attenuated Pathogenicity. J. Virol. 76: 2595-2605 [Abstract] [Full Text]  
  • Binley, J. M., Sanders, R. W., Master, A., Cayanan, C. S., Wiley, C. L., Schiffner, L., Travis, B., Kuhmann, S., Burton, D. R., Hu, S.-L., Olson, W. C., Moore, J. P. (2002). Enhancing the Proteolytic Maturation of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins. J. Virol. 76: 2606-2616 [Abstract] [Full Text]  
  • Srivastava, I. K., Stamatatos, L., Legg, H., Kan, E., Fong, A., Coates, S. R., Leung, L., Wininger, M., Donnelly, J. J., Ulmer, J. B., Barnett, S. W. (2002). Purification and Characterization of Oligomeric Envelope Glycoprotein from a Primary R5 Subtype B Human Immunodeficiency Virus. J. Virol. 76: 2835-2847 [Abstract] [Full Text]  
  • Yang, X., Wyatt, R., Sodroski, J. (2001). Improved Elicitation of Neutralizing Antibodies against Primary Human Immunodeficiency Viruses by Soluble Stabilized Envelope Glycoprotein Trimers. J. Virol. 75: 1165-1171 [Abstract] [Full Text]  
  • Salzwedel, K., Berger, E. A. (2000). Cooperative subunit interactions within the oligomeric envelope glycoprotein of HIV-1: Functional complementation of specific defects in gp120 and gp41. Proc. Natl. Acad. Sci. USA 10.1073/pnas.230438497v1 [Abstract] [Full Text]  
  • Maerz, A. L., Center, R. J., Kemp, B. E., Kobe, B., Poumbourios, P. (2000). Functional Implications of the Human T-Lymphotropic Virus Type 1 Transmembrane Glycoprotein Helical Hairpin Structure. J. Virol. 74: 6614-6621 [Abstract] [Full Text]  
  • Yang, X., Farzan, M., Wyatt, R., Sodroski, J. (2000). Characterization of Stable, Soluble Trimers Containing Complete Ectodomains of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins. J. Virol. 74: 5716-5725 [Abstract] [Full Text]  
  • Sanders, R. W., Schiffner, L., Master, A., Kajumo, F., Guo, Y., Dragic, T., Moore, J. P., Binley, J. M. (2000). Variable-Loop-Deleted Variants of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Can Be Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits. J. Virol. 74: 5091-5100 [Abstract] [Full Text]  
  • Yang, X., Florin, L., Farzan, M., Kolchinsky, P., Kwong, P. D., Sodroski, J., Wyatt, R. (2000). Modifications That Stabilize Human Immunodeficiency Virus Envelope Glycoprotein Trimers in Solution. J. Virol. 74: 4746-4754 [Abstract] [Full Text]  
  • Kwong, P. D., Wyatt, R., Sattentau, Q. J., Sodroski, J., Hendrickson, W. A. (2000). Oligomeric Modeling and Electrostatic Analysis of the gp120 Envelope Glycoprotein of Human Immunodeficiency Virus. J. Virol. 74: 1961-1972 [Abstract] [Full Text]  
  • Binley, J. M., Sanders, R. W., Clas, B., Schuelke, N., Master, A., Guo, Y., Kajumo, F., Anselma, D. J., Maddon, P. J., Olson, W. C., Moore, J. P. (2000). A Recombinant Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Complex Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits Is an Antigenic Mimic of the Trimeric Virion-Associated Structure. J. Virol. 74: 627-643 [Abstract] [Full Text]  
  • Louis, J. M., Bewley, C. A., Clore, G. M. (2001). Design and Properties of NCCG-gp41, a Chimeric gp41 Molecule with Nanomolar HIV Fusion Inhibitory Activity. J. Biol. Chem. 276: 29485-29489 [Abstract] [Full Text]  
  • Staropoli, I., Chanel, C., Girard, M., Altmeyer, R. (2000). Processing, Stability, and Receptor Binding Properties of Oligomeric Envelope Glycoprotein from a Primary HIV-1 Isolate. J. Biol. Chem. 275: 35137-35145 [Abstract] [Full Text]  
  • Chen, B., Zhou, G., Kim, M., Chishti, Y., Hussey, R. E., Ely, B., Skehel, J. J., Reinherz, E. L., Harrison, S. C., Wiley, D. C. (2000). Expression, Purification, and Characterization of gp160e, the Soluble, Trimeric Ectodomain of the Simian Immunodeficiency Virus Envelope Glycoprotein, gp160. J. Biol. Chem. 275: 34946-34953 [Abstract] [Full Text]  
  • Schnell, M. J., Foley, H. D., Siler, C. A., McGettigan, J. P., Dietzschold, B., Pomerantz, R. J. (2000). Recombinant rabies virus as potential live-viral vaccines for HIV-1. Proc. Natl. Acad. Sci. USA 97: 3544-3549 [Abstract] [Full Text]  
  • Salzwedel, K., Berger, E. A. (2000). Cooperative subunit interactions within the oligomeric envelope glycoprotein of HIV-1: Functional complementation of specific defects in gp120 and gp41. Proc. Natl. Acad. Sci. USA 97: 12794-12799 [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»