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, March 2001, p. 2041-2050, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2041-2050.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Increased Neutralization Sensitivity of CD4-Independent Human Immunodeficiency Virus Variants

Peter Kolchinsky,1 Enko Kiprilov,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 21 July 2000/Accepted 1 December 2000

Naturally occurring human immunodeficiency virus (HIV-1) variants require the presence of CD4 and specific chemokine receptors to enter a cell. In the laboratory, HIV-1 variants that are capable of bypassing CD4 and utilizing only the CCR5 chemokine receptor for virus entry have been generated. Here we report that these CD4-independent viruses are significantly more sensitive to neutralization by soluble CD4 and a variety of antibodies. The same amino acid changes in the HIV-1 gp120 envelope glycoprotein determined CD4 independence and neutralization sensitivity. The CD4-independent envelope glycoproteins exhibited higher affinity for antibodies against CD4-induced gp120 epitopes but not other neutralizing ligands. The CD4-independent envelope glycoproteins did not exhibit increased lability relative to the wild-type envelope glycoproteins. The utilization of two receptors apparently allows HIV-1 to maintain a more neutralization-resistant state prior to engaging CD4 on the target cell, explaining the rarity of CD4 independence in wild-type HIV-1.

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

Journal of Virology, March 2001, p. 2041-2050, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2041-2050.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Vermeire, K., Van Laethem, K., Janssens, W., Bell, T. W., Schols, D. (2009). Human Immunodeficiency Virus Type 1 Escape from Cyclotriazadisulfonamide-Induced CD4-Targeted Entry Inhibition Is Associated with Increased Neutralizing Antibody Susceptibility. J. Virol. 83: 9577-9583 [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]  
  • Binley, J. M., Lybarger, E. A., Crooks, E. T., Seaman, M. S., Gray, E., Davis, K. L., Decker, J. M., Wycuff, D., Harris, L., Hawkins, N., Wood, B., Nathe, C., Richman, D., Tomaras, G. D., Bibollet-Ruche, F., Robinson, J. E., Morris, L., Shaw, G. M., Montefiori, D. C., Mascola, J. R. (2008). Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C. J. Virol. 82: 11651-11668 [Abstract] [Full Text]  
  • Taylor, B. M., Foulke, J. S., Flinko, R., Heredia, A., DeVico, A., Reitz, M. (2008). An Alteration of Human Immunodeficiency Virus gp41 Leads to Reduced CCR5 Dependence and CD4 Independence. J. Virol. 82: 5460-5471 [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]  
  • Kubo, Y., Yokoyama, M., Yoshii, H., Mitani, C., Tominaga, C., Tanaka, Y., Sato, H., Yamamoto, N. (2007). Inhibitory role of CXCR4 glycan in CD4-independent X4-tropic human immunodeficiency virus type 1 infection and its abrogation in CD4-dependent infection. J. Gen. Virol. 88: 3139-3144 [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]  
  • Li, M., Salazar-Gonzalez, J. F., Derdeyn, C. A., Morris, L., Williamson, C., Robinson, J. E., Decker, J. M., Li, Y., Salazar, M. G., Polonis, V. R., Mlisana, K., Karim, S. A., Hong, K., Greene, K. M., Bilska, M., Zhou, J., Allen, S., Chomba, E., Mulenga, J., Vwalika, C., Gao, F., Zhang, M., Korber, B. T. M., Hunter, E., Hahn, B. H., Montefiori, D. C. (2006). Genetic and Neutralization Properties of Subtype C Human Immunodeficiency Virus Type 1 Molecular env Clones from Acute and Early Heterosexually Acquired Infections in Southern Africa. J. Virol. 80: 11776-11790 [Abstract] [Full Text]  
  • Willett, B. J., McMonagle, E. L., Ridha, S., Hosie, M. J. (2006). Differential Utilization of CD134 as a Functional Receptor by Diverse Strains of Feline Immunodeficiency Virus.. J. Virol. 80: 3386-3394 [Abstract] [Full Text]  
  • Moore, P. L., Crooks, E. T., Porter, L., Zhu, P., Cayanan, C. S., Grise, H., Corcoran, P., Zwick, M. B., Franti, M., Morris, L., Roux, K. H., Burton, D. R., Binley, J. M. (2006). Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1. J. Virol. 80: 2515-2528 [Abstract] [Full Text]  
  • Amberg, S. M., Netter, R. C., Simmons, G., Bates, P. (2006). Expanded Tropism and Altered Activation of a Retroviral Glycoprotein Resistant to an Entry Inhibitor Peptide. J. Virol. 80: 353-359 [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]  
  • Steckbeck, J. D., Orlov, I., Chow, A., Grieser, H., Miller, K., Bruno, J., Robinson, J. E., Montelaro, R. C., Cole, K. S. (2005). Kinetic Rates of Antibody Binding Correlate with Neutralization Sensitivity of Variant Simian Immunodeficiency Virus Strains. J. Virol. 79: 12311-12320 [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]  
  • Pancera, M., Lebowitz, J., Schon, A., Zhu, P., Freire, E., Kwong, P. D., Roux, K. H., Sodroski, J., Wyatt, R. (2005). Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with a Heterologous Trimerization Motif: Characterization and Ligand Binding Analysis. J. Virol. 79: 9954-9969 [Abstract] [Full Text]  
  • Vermeire, K., Schols, D. (2005). Cyclotriazadisulfonamides: promising new CD4-targeted anti-HIV drugs. J Antimicrob Chemother 56: 270-272 [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]  
  • Overholser, E. D., Babas, T., Zink, M. C., Barber, S. A., Clements, J. E. (2005). CD4-Independent Entry and Replication of Simian Immunodeficiency Virus in Primary Rhesus Macaque Astrocytes Are Regulated by the Transmembrane Protein. J. Virol. 79: 4944-4951 [Abstract] [Full Text]  
  • Borda, J. T., Alvarez, X., Kondova, I., Aye, P., Simon, M. A., Desrosiers, R. C., Lackner, A. A. (2004). Cell Tropism of Simian Immunodeficiency Virus in Culture Is Not Predictive of in Vivo Tropism or Pathogenesis. Am. J. Pathol. 165: 2111-2122 [Abstract] [Full Text]  
  • Pohlmann, S., Davis, C., Meister, S., Leslie, G. J., Otto, C., Reeves, J. D., Puffer, B. A., Papkalla, A., Krumbiegel, M., Marzi, A., Lorenz, S., Munch, J., Doms, R. W., Kirchhoff, F. (2004). Amino Acid 324 in the Simian Immunodeficiency Virus SIVmac V3 Loop Can Confer CD4 Independence and Modulate the Interaction with CCR5 and Alternative Coreceptors. J. Virol. 78: 3223-3232 [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]  
  • Vermeire, K., Schols, D. (2003). Specific CD4 down-modulating compounds with potent anti-HIV activity. J. Leukoc. Biol. 74: 667-675 [Abstract] [Full Text]  
  • Johnson, W. E., Sanford, H., Schwall, L., Burton, D. R., Parren, P. W. H. I., Robinson, J. E., Desrosiers, R. C. (2003). Assorted Mutations in the Envelope Gene of Simian Immunodeficiency Virus Lead to Loss of Neutralization Resistance against Antibodies Representing a Broad Spectrum of Specificities. J. Virol. 77: 9993-10003 [Abstract] [Full Text]  
  • Binley, J. M., Cayanan, C. S., Wiley, C., Schulke, N., Olson, W. C., Burton, D. R. (2003). Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions. J. Virol. 77: 5678-5684 [Abstract] [Full Text]  
  • Montefiori, D. C., Altfeld, M., Lee, P. K., Bilska, M., Zhou, J., Johnston, M. N., Gao, F., Walker, B. D., Rosenberg, E. S. (2003). Viremia Control Despite Escape from a Rapid and Potent Autologous Neutralizing Antibody Response After Therapy Cessation in an HIV-1-Infected Individual. J. Immunol. 170: 3906-3914 [Abstract] [Full Text]  
  • Vermeire, K., Bell, T. W., Choi, H.-J., Jin, Q., Samala, M. F., Sodoma, A., De Clercq, E., Schols, D. (2003). The Anti-HIV Potency of Cyclotriazadisulfonamide Analogs Is Directly Correlated with Their Ability to Down-Modulate the CD4 Receptor. Mol. Pharmacol. 63: 203-210 [Abstract] [Full Text]  
  • Johnson, W. E., Lifson, J. D., Lang, S. M., Johnson, R. P., Desrosiers, R. C. (2002). Importance of B-Cell Responses for Immunological Control of Variant Strains of Simian Immunodeficiency Virus. J. Virol. 77: 375-381 [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]  
  • Fouts, T., Godfrey, K., Bobb, K., Montefiori, D., Hanson, C. V., Kalyanaraman, V. S., DeVico, A., Pal, R. (2002). Crosslinked HIV-1 envelope-CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques. Proc. Natl. Acad. Sci. USA 99: 11842-11847 [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]  
  • Edwards, T. G., Wyss, S., Reeves, J. D., Zolla-Pazner, S., Hoxie, J. A., Doms, R. W., Baribaud, F. (2002). Truncation of the Cytoplasmic Domain Induces Exposure of Conserved Regions in the Ectodomain of Human Immunodeficiency Virus Type 1 Envelope Protein. J. Virol. 76: 2683-2691 [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]  
  • Lin, G., Lee, B., Haggarty, B. S., Doms, R. W., Hoxie, J. A. (2001). CD4-Independent Use of Rhesus CCR5 by Human Immunodeficiency Virus Type 2 Implicates an Electrostatic Interaction between the CCR5 N Terminus and the gp120 C4 Domain. J. Virol. 75: 10766-10778 [Abstract] [Full Text]  
  • Si, Z., Cayabyab, M., Sodroski, J. (2001). Envelope Glycoprotein Determinants of Neutralization Resistance in a Simian-Human Immunodeficiency Virus (SHIV-HXBc2P 3.2) Derived by Passage in Monkeys. J. Virol. 75: 4208-4218 [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»