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 Etemad-Moghadam, B.
Right arrow Articles by Sodroski, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Etemad-Moghadam, B.
Right arrow Articles by Sodroski, J.

 Previous Article  |  Next Article 

Journal of Virology, October 1999, p. 8873-8879, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Determinants of Neutralization Resistance in the Envelope Glycoproteins of a Simian-Human Immunodeficiency Virus Passaged In Vivo

Bijan Etemad-Moghadam,1 Ying Sun,1 Emma K. Nicholson,1 Gunilla B. Karlsson,1 Dominik Schenten,1 and Joseph Sodroski1,2,*

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

Received 29 March 1999/Accepted 7 July 1999

In vivo passage of a simian-human immunodeficiency virus (SHIV-89.6) generated a virus, SHIV-89.6P, that exhibited increased resistance to some neutralizing antibodies (G. B. Karlsson et al., J. Exp. Med. 188:1159-1171, 1998). Here we examine the range of human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies to which the passaged virus became resistant and identify envelope glycoprotein determinants of antibody resistance. Compared with the envelope glycoproteins derived from the parental SHIV-89.6, the envelope glycoproteins of the passaged virus were resistant to antibodies directed against the gp120 V3 variable loop and the CD4 binding site. By contrast, both viral envelope glycoproteins were equally sensitive to neutralization by two antibodies, 2G12 and 2F5, that recognize poorly immunogenic structures on gp120 and gp41, respectively. Changes in the V2 and V3 variable loops of gp120 were necessary and sufficient for full resistance to the IgG1b12 antibody, which is directed against the CD4 binding site. Changes in the V3 loop specified complete resistance to a V3 loop-directed antibody, while changes in the V1/V2 loops conferred partial resistance to this antibody. The epitopes of the neutralizing antibodies were not disrupted by the resistance-associated changes. These results indicate that in vivo selection occurs for HIV-1 envelope glycoproteins with variable loop conformations that restrict the access of antibodies to immunogenic neutralization epitopes.

* Corresponding author. Mailing address: Division of Human Retrovirology, 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, October 1999, p. 8873-8879, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Laird, M. E., Igarashi, T., Martin, M. A., Desrosiers, R. C. (2008). Importance of the V1/V2 Loop Region of Simian-Human Immunodeficiency Virus Envelope Glycoprotein gp120 in Determining the Strain Specificity of the Neutralizing Antibody Response. J. Virol. 82: 11054-11065 [Abstract] [Full Text]  
  • Laird, M. E., Desrosiers, R. C. (2007). Infectivity and Neutralization of Simian Immunodeficiency Virus with FLAG Epitope Insertion in gp120 Variable Loops. J. Virol. 81: 10838-10848 [Abstract] [Full Text]  
  • Harrington, P. R., Nelson, J. A. E., Kitrinos, K. M., Swanstrom, R. (2007). Independent Evolution of Human Immunodeficiency Virus Type 1 env V1/V2 and V4/V5 Hypervariable Regions during Chronic Infection. J. Virol. 81: 5413-5417 [Abstract] [Full Text]  
  • Shibata, J., Yoshimura, K., Honda, A., Koito, A., Murakami, T., Matsushita, S. (2007). Impact of V2 Mutations on Escape from a Potent Neutralizing Anti-V3 Monoclonal Antibody during In Vitro Selection of a Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol. 81: 3757-3768 [Abstract] [Full Text]  
  • Yang, X., Lipchina, I., Cocklin, S., Chaiken, I., Sodroski, J. (2006). Antibody Binding Is a Dominant Determinant of the Efficiency of Human Immunodeficiency Virus Type 1 Neutralization. J. Virol. 80: 11404-11408 [Abstract] [Full Text]  
  • Rusert, P., Kuster, H., Joos, B., Misselwitz, B., Gujer, C., Leemann, C., Fischer, M., Stiegler, G., Katinger, H., Olson, W. C., Weber, R., Aceto, L., Gunthard, H. F., Trkola, A. (2005). Virus Isolates during Acute and Chronic Human Immunodeficiency Virus Type 1 Infection Show Distinct Patterns of Sensitivity to Entry Inhibitors. J. Virol. 79: 8454-8469 [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]  
  • Painter, S. L., Biek, R., Holley, D. C., Poss, M. (2003). Envelope Variants from Women Recently Infected with Clade A Human Immunodeficiency Virus Type 1 Confer Distinct Phenotypes That Are Discerned by Competition and Neutralization Experiments. J. Virol. 77: 8448-8461 [Abstract] [Full Text]  
  • Kitrinos, K. M., Hoffman, N. G., Nelson, J. A. E., Swanstrom, R. (2003). Turnover of env Variable Region 1 and 2 Genotypes in Subjects with Late-Stage Human Immunodeficiency Virus Type 1 Infection. J. Virol. 77: 6811-6822 [Abstract] [Full Text]  
  • Herrera, C., Spenlehauer, C., Fung, M. S., Burton, D. R., Beddows, S., Moore, J. P. (2002). Nonneutralizing Antibodies to the CD4-Binding Site on the gp120 Subunit of Human Immunodeficiency Virus Type 1 Do Not Interfere with the Activity of a Neutralizing Antibody against the Same Site. J. Virol. 77: 1084-1091 [Abstract] [Full Text]  
  • Hofmann-Lehmann, R., Vlasak, J., Chenine, A.-L., Li, P.-L., Baba, T. W., Montefiori, D. C., McClure, H. M., Anderson, D. C., Ruprecht, R. M. (2002). Molecular Evolution of Human Immunodeficiency Virus env in Humans and Monkeys: Similar Patterns Occur during Natural Disease Progression or Rapid Virus Passage. J. Virol. 76: 5278-5284 [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]  
  • Hofmann-Lehmann, R., Vlasak, J., Rasmussen, R. A., Smith, B. A., Baba, T. W., Liska, V., Ferrantelli, F., Montefiori, D. C., McClure, H. M., Anderson, D. C., Bernacky, B. J., Rizvi, T. A., Schmidt, R., Hill, L. R., Keeling, M. E., Katinger, H., Stiegler, G., Cavacini, L. A., Posner, M. R., Chou, T.-C., Andersen, J., Ruprecht, R. M. (2001). Postnatal Passive Immunization of Neonatal Macaques with a Triple Combination of Human Monoclonal Antibodies against Oral Simian-Human Immunodeficiency Virus Challenge. J. Virol. 75: 7470-7480 [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]  
  • Shenoy, S. R., O'Keefe, B. R., Bolmstedt, A. J., Cartner, L. K., Boyd, M. R. (2001). Selective Interactions of the Human Immunodeficiency Virus-Inactivating Protein Cyanovirin-N with High-Mannose Oligosaccharides on gp120 and Other Glycoproteins. J. Pharmacol. Exp. Ther. 297: 704-710 [Abstract] [Full Text]  
  • Ye, Y., Si, Z. H., Moore, J. P., Sodroski, J. (2000). Association of Structural Changes in the V2 and V3 Loops of the gp120 Envelope Glycoprotein with Acquisition of Neutralization Resistance in a Simian-Human Immunodeficiency Virus Passaged In Vivo. J. Virol. 74: 11955-11962 [Abstract] [Full Text]  
  • Etemad-Moghadam, B., Sun, Y., Nicholson, E. K., Fernandes, M., Liou, K., Gomila, R., Lee, J., Sodroski, J. (2000). Envelope Glycoprotein Determinants of Increased Fusogenicity in a Pathogenic Simian-Human Immunodeficiency Virus (SHIV-KB9) Passaged In Vivo. J. Virol. 74: 4433-4440 [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»