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 Nabatov, A. A.
Right arrow Articles by Paxton, W. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nabatov, A. A.
Right arrow Articles by Paxton, W. A.

 Previous Article  |  Next Article 

Journal of Virology, January 2004, p. 524-530, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.524-530.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Alexey A. Nabatov, Georgios Pollakis, Thomas Linnemann, Aletta Kliphius, Moustapha I. M. Chalaby,{dagger} and William A. Paxton*

Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands

Received 15 July 2003/ Accepted 26 September 2003

We studied human immunodeficiency virus type 1 (HIV-1) chimeric viruses altering in their gp120 V1V2 and V3 envelope regions to better map which genetic alterations are associated with specific virus phenotypes associated with HIV-1 disease progression. The V1V2 and V3 regions studied were based on viruses isolated from an individual with progressing HIV-1 disease. Higher V3 charges were linked with CXCR4 usage, but only when considered within a specific V1V2 and V3 N-linked glycosylation context. When the virus gained R5X4 dual tropism, irrespective of its V3 charge, it became highly resistant to inhibition by RANTES and highly sensitive to inhibition by SDF-1{alpha}. R5 viruses with higher positive V3 charges were more sensitive to inhibition by RANTES, while R5X4 dualtropic viruses with higher positive V3 charges were more resistant to inhibition by SDF-1{alpha}. Loss of the V3 N-linked glycosylation event rendered the virus more resistant to inhibition by SDF-1{alpha}. The same alterations in the V1V2 and V3 regions influenced the extent to which the viruses were neutralized with soluble CD4, as well as monoclonal antibodies b12 and 2G12, but not monoclonal antibody 2F5. These results further identify a complex set of alterations within the V1V2 and V3 regions of HIV-1 that can be selected in the host via alterations of coreceptor usage, CC/CXC chemokine inhibition, CD4 binding, and antibody neutralization.

* Corresponding author. Mailing address: Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105AZ Amsterdam, The Netherlands. Phone: (31-20) 566 4739. Fax: (31-20) 691 6531. E-mail: w.a.paxton{at}amc.uva.nl.

{dagger} Present address: Genmab B.V., 3584 CK Utrecht, The Netherlands.

Journal of Virology, January 2004, p. 524-530, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.524-530.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bontjer, I., Land, A., Eggink, D., Verkade, E., Tuin, K., Baldwin, C., Pollakis, G., Paxton, W. A., Braakman, I., Berkhout, B., Sanders, R. W. (2009). Optimization of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins with V1/V2 Deleted, Using Virus Evolution. J. Virol. 83: 368-383 [Abstract] [Full Text]  
  • Joyce, J. G., Krauss, I. J., Song, H. C., Opalka, D. W., Grimm, K. M., Nahas, D. D., Esser, M. T., Hrin, R., Feng, M., Dudkin, V. Y., Chastain, M., Shiver, J. W., Danishefsky, S. J. (2008). An oligosaccharide-based HIV-1 2G12 mimotope vaccine induces carbohydrate-specific antibodies that fail to neutralize HIV-1 virions. Proc. Natl. Acad. Sci. USA 105: 15684-15689 [Abstract] [Full Text]  
  • van Montfort, T., Thomas, A. A. M., Pollakis, G., Paxton, W. A. (2008). Dendritic Cells Preferentially Transfer CXCR4-Using Human Immunodeficiency Virus Type 1 Variants to CD4+ T Lymphocytes in trans. J. Virol. 82: 7886-7896 [Abstract] [Full Text]  
  • 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]  
  • Huang, W., Toma, J., Fransen, S., Stawiski, E., Reeves, J. D., Whitcomb, J. M., Parkin, N., Petropoulos, C. J. (2008). Coreceptor Tropism Can Be Influenced by Amino Acid Substitutions in the gp41 Transmembrane Subunit of Human Immunodeficiency Virus Type 1 Envelope Protein. J. Virol. 82: 5584-5593 [Abstract] [Full Text]  
  • Voronin, Y., Chohan, B., Emerman, M., Overbaugh, J. (2007). Primary Isolates of Human Immunodeficiency Virus Type 1 Are Usually Dominated by the Major Variants Found in Blood. J. Virol. 81: 10232-10241 [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]  
  • Mild, M., Esbjornsson, J., Fenyo, E. M., Medstrand, P. (2007). Frequent Intrapatient Recombination between Human Immunodeficiency Virus Type 1 R5 and X4 Envelopes: Implications for Coreceptor Switch. J. Virol. 81: 3369-3376 [Abstract] [Full Text]  
  • van Montfort, T., Nabatov, A. A., Geijtenbeek, T. B. H., Pollakis, G., Paxton, W. A. (2007). Efficient Capture of Antibody Neutralized HIV-1 by Cells Expressing DC-SIGN and Transfer to CD4+ T Lymphocytes. J. Immunol. 178: 3177-3185 [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]  
  • Shi, Y., Brandin, E., Vincic, E., Jansson, M., Blaxhult, A., Gyllensten, K., Moberg, L., Brostrom, C., Fenyo, E. M., Albert, J. (2005). Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation. J. Gen. Virol. 86: 3385-3396 [Abstract] [Full Text]  
  • Saunders, C. J., McCaffrey, R. A., Zharkikh, I., Kraft, Z., Malenbaum, S. E., Burke, B., Cheng-Mayer, C., Stamatatos, L. (2005). The V1, V2, and V3 Regions of the Human Immunodeficiency Virus Type 1 Envelope Differentially Affect the Viral Phenotype in an Isolate-Dependent Manner. J. Virol. 79: 9069-9080 [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»