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 Kolchinsky, P.
Right arrow Articles by Sodroski, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kolchinsky, P.
Right arrow Articles by Sodroski, J.

 Previous Article  |  Next Article 

Journal of Virology, April 2001, p. 3435-3443, Vol. 75, No. 7
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.7.3435-3443.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Loss of a Single N-Linked Glycan Allows CD4-Independent Human Immunodeficiency Virus Type 1 Infection by Altering the Position of the gp120 V1/V2 Variable Loops

Peter Kolchinsky,1 Enko Kiprilov,1 Peter Bartley,1,dagger Roee Rubinstein,1 and Joseph Sodroski1,2,*

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School,1 and Department of Immunology and Infectious Diseases, Harvard School of Public Health,2 Boston, Massachusetts 02115

Received 8 June 2000/Accepted 5 January 2001

The gp120 envelope glycoprotein of primary human immunodeficiency virus type 1 (HIV-1) promotes virus entry by sequentially binding CD4 and the CCR5 chemokine receptor on the target cell. Previously, we adapted a primary HIV-1 isolate, ADA, to replicate in CD4-negative canine cells expressing human CCR5. The gp120 changes responsible for CD4-independent replication were limited to the V2 loop-V1/V2 stem. Here we show that elimination of a single glycosylation site at asparagine 197 in the V1/V2 stem is sufficient for CD4-independent gp120 binding to CCR5 and for HIV-1 entry into CD4-negative cells expressing CCR5. Deletion of the V1/V2 loops also allowed CD4-independent viral entry and gp120 binding to CCR5. The binding of the wild-type ADA gp120 to CCR5 was less dependent upon CD4 at 4°C than at 37°C. In the absence of the V1/V2 loops, neither removal of the N-linked carbohydrate at asparagine 197 nor lowering of the temperature increased the CD4-independent phenotypes. A CCR5-binding conformation of gp120, achieved by CD4 interaction or by modification of temperature, glycosylation, or variable loops, was preferentially recognized by the monoclonal antibody 48d. These results suggest that the CCR5-binding region of gp120 is occluded by the V1/V2 variable loops, the position of which can be modulated by temperature, CD4 binding, or an N-linked glycan in the V1/V2 stem.

* Corresponding author. Mailing address: Dana-Farber Cancer Institute, 44 Binney St., FB 824, Boston, MA 02115. Phone: (617) 632-3371. Fax: (617) 632-4338. E-mail: joseph_sodroski{at}dfci.harvard.edu.

dagger Present address: University of Glasgow, Glasgow, Scotland.

Journal of Virology, April 2001, p. 3435-3443, Vol. 75, No. 7
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.7.3435-3443.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Wu, X., Zhou, T., O'Dell, S., Wyatt, R. T., Kwong, P. D., Mascola, J. R. (2009). Mechanism of Human Immunodeficiency Virus Type 1 Resistance to Monoclonal Antibody b12 That Effectively Targets the Site of CD4 Attachment. J. Virol. 83: 10892-10907 [Abstract] [Full Text]  
  • Kassa, A., Madani, N., Schon, A., Haim, H., Finzi, A., Xiang, S.-H., Wang, L., Princiotto, A., Pancera, M., Courter, J., Smith, A. B. III, Freire, E., Kwong, P. D., Sodroski, J. (2009). Transitions to and from the CD4-Bound Conformation Are Modulated by a Single-Residue Change in the Human Immunodeficiency Virus Type 1 gp120 Inner Domain. J. Virol. 83: 8364-8378 [Abstract] [Full Text]  
  • Kassa, A., Finzi, A., Pancera, M., Courter, J. R., Smith, A. B. III, Sodroski, J. (2009). Identification of a Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Variant Resistant to Cold Inactivation. J. Virol. 83: 4476-4488 [Abstract] [Full Text]  
  • Pantophlet, R., Wang, M., Aguilar-Sino, R. O., Burton, D. R. (2009). The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions. J. Virol. 83: 1649-1659 [Abstract] [Full Text]  
  • Davis, K. L., Bibollet-Ruche, F., Li, H., Decker, J. M., Kutsch, O., Morris, L., Salomon, A., Pinter, A., Hoxie, J. A., Hahn, B. H., Kwong, P. D., Shaw, G. M. (2009). Human Immunodeficiency Virus Type 2 (HIV-2)/HIV-1 Envelope Chimeras Detect High Titers of Broadly Reactive HIV-1 V3-Specific Antibodies in Human Plasma. J. Virol. 83: 1240-1259 [Abstract] [Full Text]  
  • Yuste, E., Bixby, J., Lifson, J., Sato, S., Johnson, W., Desrosiers, R. (2008). Glycosylation of gp41 of Simian Immunodeficiency Virus Shields Epitopes That Can Be Targets for Neutralizing Antibodies. J. Virol. 82: 12472-12486 [Abstract] [Full Text]  
  • Sugimoto, C., Nakayama, E. E., Shioda, T., Villinger, F., Ansari, A. A., Yamamoto, N., Suzuki, Y., Nagai, Y., Mori, K. (2008). Impact of glycosylation on antigenicity of simian immunodeficiency virus SIV239: induction of rapid V1/V2-specific non-neutralizing antibody and delayed neutralizing antibody following infection with an attenuated deglycosylated mutant. J. Gen. Virol. 89: 554-566 [Abstract] [Full Text]  
  • Li, Y., Cleveland, B., Klots, I., Travis, B., Richardson, B. A., Anderson, D., Montefiori, D., Polacino, P., Hu, S.-L. (2008). Removal of a Single N-Linked Glycan in Human Immunodeficiency Virus Type 1 gp120 Results in an Enhanced Ability To Induce Neutralizing Antibody Responses. J. Virol. 82: 638-651 [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]  
  • Kraft, Z., Derby, N. R., McCaffrey, R. A., Niec, R., Blay, W. M., Haigwood, N. L., Moysi, E., Saunders, C. J., Wrin, T., Petropoulos, C. J., McElrath, M. J., Stamatatos, L. (2007). Macaques Infected with a CCR5-Tropic Simian/Human Immunodeficiency Virus (SHIV) Develop Broadly Reactive Anti-HIV Neutralizing Antibodies. J. Virol. 81: 6402-6411 [Abstract] [Full Text]  
  • Rong, R., Gnanakaran, S., Decker, J. M., Bibollet-Ruche, F., Taylor, J., Sfakianos, J. N., Mokili, J. L., Muldoon, M., Mulenga, J., Allen, S., Hahn, B. H., Shaw, G. M., Blackwell, J. L., Korber, B. T., Hunter, E., Derdeyn, C. A. (2007). Unique Mutational Patterns in the Envelope {alpha}2 Amphipathic Helix and Acquisition of Length in gp120 Hypervariable Domains Are Associated with Resistance to Autologous Neutralization of Subtype C Human Immunodeficiency Virus Type 1. J. Virol. 81: 5658-5668 [Abstract] [Full Text]  
  • Rong, R., Bibollet-Ruche, F., Mulenga, J., Allen, S., Blackwell, J. L., Derdeyn, C. A. (2007). Role of V1V2 and Other Human Immunodeficiency Virus Type 1 Envelope Domains in Resistance to Autologous Neutralization during Clade C Infection. J. Virol. 81: 1350-1359 [Abstract] [Full Text]  
  • Madani, N., Hubicki, A. M., Perdigoto, A. L., Springer, M., Sodroski, J. (2007). Inhibition of Human Immunodeficiency Virus Envelope Glycoprotein- Mediated Single Cell Lysis by Low-Molecular-Weight Antagonists of Viral Entry. J. Virol. 81: 532-538 [Abstract] [Full Text]  
  • Yang, X., Kurteva, S., Ren, X., Lee, S., Sodroski, J. (2006). Subunit Stoichiometry of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers during Virus Entry into Host Cells. J. Virol. 80: 4388-4395 [Abstract] [Full Text]  
  • Ho, H.-T., Fan, L., Nowicka-Sans, B., McAuliffe, B., Li, C.-B., Yamanaka, G., Zhou, N., Fang, H., Dicker, I., Dalterio, R., Gong, Y.-F., Wang, T., Yin, Z., Ueda, Y., Matiskella, J., Kadow, J., Clapham, P., Robinson, J., Colonno, R., Lin, P.-F. (2006). Envelope conformational changes induced by human immunodeficiency virus type 1 attachment inhibitors prevent CD4 binding and downstream entry events.. J. Virol. 80: 4017-4025 [Abstract] [Full Text]  
  • Pastore, C., Nedellec, R., Ramos, A., Pontow, S., Ratner, L., Mosier, D. E. (2006). Human Immunodeficiency Virus Type 1 Coreceptor Switching: V1/V2 Gain-of-Fitness Mutations Compensate for V3 Loss-of-Fitness Mutations. J. Virol. 80: 750-758 [Abstract] [Full Text]  
  • Wyss, S., Dimitrov, A. S., Baribaud, F., Edwards, T. G., Blumenthal, R., Hoxie, J. A. (2005). Regulation of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Fusion by a Membrane-Interactive Domain in the gp41 Cytoplasmic Tail. J. Virol. 79: 12231-12241 [Abstract] [Full Text]  
  • Pikora, C., Wittish, C., Desrosiers, R. C. (2005). Identification of Two N-Linked Glycosylation Sites within the Core of the Simian Immunodeficiency Virus Glycoprotein Whose Removal Enhances Sensitivity to Soluble CD4. J. Virol. 79: 12575-12583 [Abstract] [Full Text]  
  • Pinter, A., Honnen, W. J., D'Agostino, P., Gorny, M. K., Zolla-Pazner, S., Kayman, S. C. (2005). The C108g Epitope in the V2 Domain of gp120 Functions as a Potent Neutralization Target When Introduced into Envelope Proteins Derived from Human Immunodeficiency Virus Type 1 Primary Isolates. J. Virol. 79: 6909-6917 [Abstract] [Full Text]  
  • Brown, B. K., Darden, J. M., Tovanabutra, S., Oblander, T., Frost, J., Sanders-Buell, E., de Souza, M. S., Birx, D. L., McCutchan, F. E., Polonis, V. R. (2005). Biologic and Genetic Characterization of a Panel of 60 Human Immunodeficiency Virus Type 1 Isolates, Representing Clades A, B, C, D, CRF01_AE, and CRF02_AG, for the Development and Assessment of Candidate Vaccines. J. Virol. 79: 6089-6101 [Abstract] [Full Text]  
  • Decker, J. M., Bibollet-Ruche, F., Wei, X., Wang, S., Levy, D. N., Wang, W., Delaporte, E., Peeters, M., Derdeyn, C. A., Allen, S., Hunter, E., Saag, M. S., Hoxie, J. A., Hahn, B. H., Kwong, P. D., Robinson, J. E., Shaw, G. M. (2005). Antigenic conservation and immunogenicity of the HIV coreceptor binding site. JEM 201: 1407-1419 [Abstract] [Full Text]  
  • Ren, X., Sodroski, J., Yang, X. (2005). An Unrelated Monoclonal Antibody Neutralizes Human Immunodeficiency Virus Type 1 by Binding to an Artificial Epitope Engineered in a Functionally Neutral Region of the Viral Envelope Glycoproteins. J. Virol. 79: 5616-5624 [Abstract] [Full Text]  
  • Walter, B. L., Wehrly, K., Swanstrom, R., Platt, E., Kabat, D., Chesebro, B. (2005). Role of Low CD4 Levels in the Influence of Human Immunodeficiency Virus Type 1 Envelope V1 and V2 Regions on Entry and Spread in Macrophages. J. Virol. 79: 4828-4837 [Abstract] [Full Text]  
  • Platt, E. J., Shea, D. M., Rose, P. P., Kabat, D. (2005). Variants of Human Immunodeficiency Virus Type 1 That Efficiently Use CCR5 Lacking the Tyrosine-Sulfated Amino Terminus Have Adaptive Mutations in gp120, Including Loss of a Functional N-Glycan. J. Virol. 79: 4357-4368 [Abstract] [Full Text]  
  • McCaffrey, R. A., Saunders, C., Hensel, M., Stamatatos, L. (2004). N-Linked Glycosylation of the V3 Loop and the Immunologically Silent Face of gp120 Protects Human Immunodeficiency Virus Type 1 SF162 from Neutralization by Anti-gp120 and Anti-gp41 Antibodies. J. Virol. 78: 3279-3295 [Abstract] [Full Text]  
  • Madani, N., Perdigoto, A. L., Srinivasan, K., Cox, J. M., Chruma, J. J., LaLonde, J., Head, M., Smith, A. B. III, Sodroski, J. G. (2004). Localized Changes in the gp120 Envelope Glycoprotein Confer Resistance to Human Immunodeficiency Virus Entry Inhibitors BMS-806 and #155. J. Virol. 78: 3742-3752 [Abstract] [Full Text]  
  • Derdeyn, C. A., Decker, J. M., Bibollet-Ruche, F., Mokili, J. L., Muldoon, M., Denham, S. A., Heil, M. L., Kasolo, F., Musonda, R., Hahn, B. H., Shaw, G. M., Korber, B. T., Allen, S., Hunter, E. (2004). Envelope-Constrained Neutralization-Sensitive HIV-1 After Heterosexual Transmission. Science 303: 2019-2022 [Abstract] [Full Text]  
  • Cole, K. S., Steckbeck, J. D., Rowles, J. L., Desrosiers, R. C., Montelaro, R. C. (2004). Removal of N-Linked Glycosylation Sites in the V1 Region of Simian Immunodeficiency Virus gp120 Results in Redirection of B-Cell Responses to V3. J. Virol. 78: 1525-1539 [Abstract] [Full Text]  
  • Nabatov, A. A., Pollakis, G., Linnemann, T., Kliphius, A., Chalaby, M. I. M., Paxton, W. A. (2004). Intrapatient Alterations in the Human Immunodeficiency Virus Type 1 gp120 V1V2 and V3 Regions Differentially Modulate Coreceptor Usage, Virus Inhibition by CC/CXC Chemokines, Soluble CD4, and the b12 and 2G12 Monoclonal Antibodies. J. Virol. 78: 524-530 [Abstract] [Full Text]  
  • Guo, Q., Ho, H.-T., Dicker, I., Fan, L., Zhou, N., Friborg, J., Wang, T., McAuliffe, B. V., Wang, H.-g. H., Rose, R. E., Fang, H., Scarnati, H. T., Langley, D. R., Meanwell, N. A., Abraham, R., Colonno, R. J., Lin, P.-f. (2003). Biochemical and Genetic Characterizations of a Novel Human Immunodeficiency Virus Type 1 Inhibitor That Blocks gp120-CD4 Interactions. J. Virol. 77: 10528-10536 [Abstract] [Full Text]  
  • Labrijn, A. F., Poignard, P., Raja, A., Zwick, M. B., Delgado, K., Franti, M., Binley, J., Vivona, V., Grundner, C., Huang, C.-C., Venturi, M., Petropoulos, C. J., Wrin, T., Dimitrov, D. S., Robinson, J., Kwong, P. D., Wyatt, R. T., Sodroski, J., Burton, D. R. (2003). Access of Antibody Molecules to the Conserved Coreceptor Binding Site on Glycoprotein gp120 Is Sterically Restricted on Primary Human Immunodeficiency Virus Type 1. J. Virol. 77: 10557-10565 [Abstract] [Full Text]  
  • LaBonte, J. A., Madani, N., Sodroski, J. (2003). Cytolysis by CCR5-Using Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Is Dependent on Membrane Fusion and Can Be Inhibited by High Levels of CD4 Expression. J. Virol. 77: 6645-6659 [Abstract] [Full Text]  
  • Dehghani, H., Puffer, B. A., Doms, R. W., Hirsch, V. M. (2003). Unique Pattern of Convergent Envelope Evolution in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques: Association with CD4-Independent Usage of CCR5. J. Virol. 77: 6405-6418 [Abstract] [Full Text]  
  • Pantophlet, R., Ollmann Saphire, E., Poignard, P., Parren, P. W. H. I., Wilson, I. A., Burton, D. R. (2002). Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120. J. Virol. 77: 642-658 [Abstract] [Full Text]  
  • Raja, A., Venturi, M., Kwong, P., Sodroski, J. (2002). CD4 Binding Site Antibodies Inhibit Human Immunodeficiency Virus gp120 Envelope Glycoprotein Interaction with CCR5. J. Virol. 77: 713-718 [Abstract] [Full Text]  
  • Imamichi, H., Igarashi, T., Imamichi, T., Donau, O. K., Endo, Y., Nishimura, Y., Willey, R. L., Suffredini, A. F., Lane, H. C., Martin, M. A. (2002). Amino acid deletions are introduced into the V2 region of gp120 during independent pathogenic simian immunodeficiency virus/HIV chimeric virus (SHIV) infections of rhesus monkeys generating variants that are macrophage tropic. Proc. Natl. Acad. Sci. USA 99: 13813-13818 [Abstract] [Full Text]  
  • Basmaciogullari, S., Babcock, G. J., Van Ryk, D., Wojtowicz, W., Sodroski, J. (2002). Identification of Conserved and Variable Structures in the Human Immunodeficiency Virus gp120 Glycoprotein of Importance for CXCR4 Binding. J. Virol. 76: 10791-10800 [Abstract] [Full Text]  
  • Wojtowicz, W. M., Farzan, M., Joyal, J. L., Carter, K., Babcock, G. J., Israel, D. I., Sodroski, J., Mirzabekov, T. (2002). Stimulation of Enveloped Virus Infection by beta -Amyloid Fibrils. J. Biol. Chem. 277: 35019-35024 [Abstract] [Full Text]  
  • Xiang, S.-H., Kwong, P. D., Gupta, R., Rizzuto, C. D., Casper, D. J., Wyatt, R., Wang, L., Hendrickson, W. A., Doyle, M. L., Sodroski, J. (2002). Mutagenic Stabilization and/or Disruption of a CD4-Bound State Reveals Distinct Conformations of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein. J. Virol. 76: 9888-9899 [Abstract] [Full Text]  
  • Ryzhova, E., Whitbeck, J. C., Canziani, G., Westmoreland, S. V., Cohen, G. H., Eisenberg, R. J., Lackner, A., Gonzalez-Scarano, F. (2002). Rapid Progression to Simian AIDS Can Be Accompanied by Selection of CD4-Independent gp120 Variants with Impaired Ability To Bind CD4. J. Virol. 76: 7903-7909 [Abstract] [Full Text]  
  • Gorry, P. R., Taylor, J., Holm, G. H., Mehle, A., Morgan, T., Cayabyab, M., Farzan, M., Wang, H., Bell, J. E., Kunstman, K., Moore, J. P., Wolinsky, S. M., Gabuzda, D. (2002). Increased CCR5 Affinity and Reduced CCR5/CD4 Dependence of a Neurovirulent Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol. 76: 6277-6292 [Abstract] [Full Text]  
  • Johnson, W. E., Morgan, J., Reitter, J., Puffer, B. A., Czajak, S., Doms, R. W., Desrosiers, R. C. (2002). A Replication-Competent, Neutralization-Sensitive Variant of Simian Immunodeficiency Virus Lacking 100 Amino Acids of Envelope. J. Virol. 76: 2075-2086 [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]  
  • Chakrabarti, L. A., Ivanovic, T., Cheng-Mayer, C. (2002). Properties of the Surface Envelope Glycoprotein Associated with Virulence of Simian-Human Immunodeficiency Virus SHIVSF33A Molecular Clones. J. Virol. 76: 1588-1599 [Abstract] [Full Text]  
  • Zhu, C.-B., Zhu, L., Holz-Smith, S., Matthews, T. J., Chen, C. H. (2001). The role of the third beta strand in gp120 conformation and neutralization sensitivity of the HIV-1 primary isolate DH012. Proc. Natl. Acad. Sci. USA 10.1073/pnas.261359098v1 [Abstract] [Full Text]  
  • Gorry, P. R., Bristol, G., Zack, J. A., Ritola, K., Swanstrom, R., Birch, C. J., Bell, J. E., Bannert, N., Crawford, K., Wang, H., Schols, D., De Clercq, E., Kunstman, K., Wolinsky, S. M., Gabuzda, D. (2001). Macrophage Tropism of Human Immunodeficiency Virus Type 1 Isolates from Brain and Lymphoid Tissues Predicts Neurotropism Independent of Coreceptor Specificity. J. Virol. 75: 10073-10089 [Abstract] [Full Text]  
  • Babcock, G. J., Mirzabekov, T., Wojtowicz, W., Sodroski, J. (2001). Ligand Binding Characteristics of CXCR4 Incorporated into Paramagnetic Proteoliposomes. J. Biol. Chem. 276: 38433-38440 [Abstract] [Full Text]  
  • Zhu, C.-B., Zhu, L., Holz-Smith, S., Matthews, T. J., Chen, C. H. (2001). The role of the third beta strand in gp120 conformation and neutralization sensitivity of the HIV-1 primary isolate DH012. Proc. Natl. Acad. Sci. USA 98: 15227-15232 [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»