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 Park, E. J.
Right arrow Articles by Quinnan, G. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Park, E. J.
Right arrow Articles by Quinnan, G. V., Jr.

 Previous Article  |  Next Article 

Journal of Virology, May 2000, p. 4183-4191, Vol. 74, No. 9
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Global Neutralization Resistance Phenotype of Human Immunodeficiency Virus Type 1 Is Determined by Distinct Mechanisms Mediating Enhanced Infectivity and Conformational Change of the Envelope Complex

Eun Ju Park,1 Miroslav K. Gorny,2 Susan Zolla-Pazner,2,3 and Gerald V. Quinnan Jr.1,*

Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 208141; New York University School of Medicine, New York, New York 100162; and Research Center for AIDS and HIV Infection, Veterans Affairs Medical Center, New York, New York 100103

Received 2 August 1999/Accepted 25 January 2000

We have described previously genetic characterization of neutralization-resistant, high-infectivity, and neutralization-sensitive, low-infectivity mutants of human immunodeficiency virus type 1 (HIV-1) MN envelope. The distinct phenotypes of these clones are attributable to six mutations affecting functional interactions between the gp120 C4-V5 regions and the gp41 leucine zipper. In the present study we examined mechanisms responsible for the phenotypic differences between these envelopes using neutralization and immunofluorescence assays (IFA). Most monoclonal antibodies (MAbs) tested against gp120 epitopes (V3, CD4 binding site, and CD4-induced) were 20 to 100 times more efficient at neutralizing pseudovirus expressing sensitive rather than resistant envelope. By IFA cells expressing neutralization sensitive envelope bound MAbs to gp120 epitopes more, but gp41 epitopes less, than neutralization-resistant envelope. This binding difference appeared to reflect conformational change, since it did not correlate with the level of protein expression or gp120-gp41 dissociation. This conformational change was mostly attributable to one mutation, L544P, which contributes to neutralization resistance but not to infectivity enhancement. The V420I mutation, which contributes a major effect to both high infectivity and neutralization resistance, had no apparent effect on conformation. Notably, a conformation-dependent V3 neutralization epitope remained sensitive to neutralization and accessible to binding by MAbs on neutralization-resistant HIV-1 envelope. Sensitivity to sCD4 did not distinguish the clones, suggesting that the phenotypes may be related to post-CD4-binding effects. The results demonstrate that neutralization resistance can be determined by distinguishable effects of mutations, which cause changes in envelope conformation and/or function(s) related to infectivity. A conformation-dependent V3 epitope may be an important target for neutralization of resistant strains of HIV-1.

* Corresponding author. Mailing address: Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814. Phone: (301) 295-3734. Fax: (301) 295-1971. E-mail: gqinnan{at}USUHS.mil.

Journal of Virology, May 2000, p. 4183-4191, Vol. 74, No. 9
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Chien, M.-P., Jiang, S., Chang, D.-K. (2008). The function of coreceptor as a basis for the kinetic dissection of HIV type 1 envelope protein-mediated cell fusion. FASEB J. 22: 1179-1192 [Abstract] [Full Text]  
  • Blay, W. M., Kasprzyk, T., Misher, L., Richardson, B. A., Haigwood, N. L. (2007). Mutations in Envelope gp120 Can Impact Proteolytic Processing of the gp160 Precursor and Thereby Affect Neutralization Sensitivity of Human Immunodeficiency Virus Type 1 Pseudoviruses. J. Virol. 81: 13037-13049 [Abstract] [Full Text]  
  • Zhang, M.-Y., Xiao, X., Sidorov, I. A., Choudhry, V., Cham, F., Zhang, P. F., Bouma, P., Zwick, M., Choudhary, A., Montefiori, D. C., Broder, C. C., Burton, D. R., Quinnan, G. V. Jr., Dimitrov, D. S. (2004). Identification and Characterization of a New Cross-Reactive Human Immunodeficiency Virus Type 1-Neutralizing Human Monoclonal Antibody. J. Virol. 78: 9233-9242 [Abstract] [Full Text]  
  • Gorny, M. K., Revesz, K., Williams, C., Volsky, B., Louder, M. K., Anyangwe, C. A., Krachmarov, C., Kayman, S. C., Pinter, A., Nadas, A., Nyambi, P. N., Mascola, J. R., Zolla-Pazner, S. (2004). The V3 Loop Is Accessible on the Surface of Most Human Immunodeficiency Virus Type 1 Primary Isolates and Serves as a Neutralization Epitope. J. Virol. 78: 2394-2404 [Abstract] [Full Text]  
  • Pistello, M., Matteucci, D., Giannecchini, S., Bonci, F., Sichi, O., Presciuttini, S., Bendinelli, M. (2003). Evolution of Two Amino Acid Positions Governing Broad Neutralization Resistance in a Strain of Feline Immunodeficiency Virus over 7 Years of Persistence in Cats. CVI 10: 1109-1116 [Abstract] [Full Text]  
  • Bouma, P., Leavitt, M., Zhang, P. F., Sidorov, I. A., Dimitrov, D. S., Quinnan, G. V. Jr. (2003). Multiple Interactions across the Surface of the gp120 Core Structure Determine the Global Neutralization Resistance Phenotype of Human Immunodeficiency Virus Type 1. J. Virol. 77: 8061-8071 [Abstract] [Full Text]  
  • Dong, M., Zhang, P. F., Grieder, F., Lee, J., Krishnamurthy, G., VanCott, T., Broder, C., Polonis, V. R., Yu, X.-F., Shao, Y., Faix, D., Valente, P., Quinnan, G. V. Jr. (2003). Induction of Primary Virus-Cross-Reactive Human Immunodeficiency Virus Type 1-Neutralizing Antibodies in Small Animals by Using an Alphavirus-Derived In Vivo Expression System. J. Virol. 77: 3119-3130 [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]  
  • Leavitt, M., Park, E. J., Sidorov, I. A., Dimitrov, D. S., Quinnan, G. V. Jr. (2002). Concordant Modulation of Neutralization Resistance and High Infectivity of the Primary Human Immunodeficiency Virus Type 1 MN Strain and Definition of a Potential gp41 Binding Site in gp120. J. Virol. 77: 560-570 [Abstract] [Full Text]  
  • Gorny, M. K., Williams, C., Volsky, B., Revesz, K., Cohen, S., Polonis, V. R., Honnen, W. J., Kayman, S. C., Krachmarov, C., Pinter, A., Zolla-Pazner, S. (2002). Human Monoclonal Antibodies Specific for Conformation-Sensitive Epitopes of V3 Neutralize Human Immunodeficiency Virus Type 1 Primary Isolates from Various Clades. J. Virol. 76: 9035-9045 [Abstract] [Full Text]  
  • Zhang, P. F., Bouma, P., Park, E. J., Margolick, J. B., Robinson, J. E., Zolla-Pazner, S., Flora, M. N., Quinnan, G. V. Jr (2002). A Variable Region 3 (V3) Mutation Determines a Global Neutralization Phenotype and CD4-Independent Infectivity of a Human Immunodeficiency Virus Type 1 Envelope Associated with a Broadly Cross-Reactive, Primary Virus-Neutralizing Antibody Response. J. Virol. 76: 644-655 [Abstract] [Full Text]  
  • Giannecchini, S., Matteucci, D., Ferrari, A., Pistello, M., Bendinelli, M. (2001). Feline Immunodeficiency Virus-Infected Cat Sera Associated with the Development of Broad Neutralization Resistance In Vivo Drive Similar Reversions In Vitro. J. Virol. 75: 8868-8873 [Abstract] [Full Text]  
  • Moore, J. P., Parren, P. W. H. I., Burton, D. R. (2001). Genetic Subtypes, Humoral Immunity, and Human Immunodeficiency Virus Type 1 Vaccine Development. J. Virol. 75: 5721-5729 [Full Text]  
  • Bendinelli, M., Pistello, M., Del Mauro, D., Cammarota, G., Maggi, F., Leonildi, A., Giannecchini, S., Bergamini, C., Matteucci, D. (2001). During Readaptation In Vivo, a Tissue Culture-Adapted Strain of Feline Immunodeficiency Virus Reverts to Broad Neutralization Resistance at Different Times in Individual Hosts but through Changes at the Same Position of the Surface Glycoprotein. J. Virol. 75: 4584-4593 [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]  
  • Nyambi, P. N., Nádas, A., Mbah, H. A., Burda, S., Williams, C., Gorny, M. K., Zolla-Pazner, S. (2000). Immunoreactivity of Intact Virions of Human Immunodeficiency Virus Type 1 (HIV-1) Reveals the Existence of Fewer HIV-1 Immunotypes than Genotypes. J. Virol. 74: 10670-10680 [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»