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 Bures, R.
Right arrow Articles by Montefiori, D. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bures, R.
Right arrow Articles by Montefiori, D. C.

 Previous Article  |  Next Article 

Journal of Virology, March 2002, p. 2233-2244, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2233-2244.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Regional Clustering of Shared Neutralization Determinants on Primary Isolates of Clade C Human Immunodeficiency Virus Type 1 from South Africa

*** Renata Bures,1 Lynn Morris,2 Carolyn Williamson,3 Gita Ramjee,4 Mark Deers,5 Susan A. Fiscus,6 Salim Abdool-Karim,4 and David C. Montefiori1*

Department of Surgery, Duke University Medical Center, Durham,1 Center for AIDS Research, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,6 National Institute for Virology, Johannesburg,2 Division of Medical Virology, University of Cape Town, Cape Town,3 Medical Research Council, Durban, South Africa,4 Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington 981095

Received 27 July 2001/ Accepted 20 September 2001

Clade C is one of the most prevalent genetic subtypes of human immunodeficiency virus type 1 (HIV-1) in the world today and one of the least studied with respect to neutralizing antibodies. Most information on HIV-1 serology as it relates to neutralization is derived from clade B. Clade C primary isolates of HIV-1 from South Africa and Malawi were shown here to resemble clade B isolates in their resistance to inhibition by soluble CD4 and their sensitivity to neutralization by human monoclonal antibody immunoglobulin G1b12 and, to a lesser extent, 2F5. Unlike clade B isolates, however, all 16 clade C isolates examined resisted neutralization by 2G12. Infection with clade C HIV-1 in a cohort of female sex workers in South Africa generated antibodies that neutralized the autologous clade C isolate and T-cell-line-adapted (TCLA) strains of clade B. Neutralization of clade B TCLA strains was much more sensitive to the presence of autologous gp120 V3 loop peptides compared to the neutralization of clade C isolates in most cases. Thus, the native structure of gp120 on primary isolates of clade C will likely pose a challenge for neutralizing antibody induction by candidate HIV-1 vaccines much the same as it has for clade B. The autologous neutralizing antibody response following primary infection with clade C HIV-1 in South Africa matured slowly, requiring at least 4 to 5 months to become detectable. Once detectable, extensive cross-neutralization of heterologous clade C isolates from South Africa was observed, suggesting an unusual degree of shared neutralization determinants at a regional level. This high frequency of cross-neutralization differed significantly from the ability of South African clade C serum samples to neutralize clade B isolates but did not differ significantly from results of other combinations of clade B and C reagents tested in checkerboard assays. Notably, two clade C serum samples obtained after less than 2 years of infection neutralized a broad spectrum of clade B and C isolates. Other individual serum samples showed a significant clade preference in their neutralizing activity. Our results suggest that clades B and C are each comprised of multiple neutralization serotypes, some of which are more clade specific than others. The clustering of shared neutralization determinants on clade C primary HIV-1 isolates from South Africa suggests that neutralizing antibodies induced by vaccines will have less epitope diversity to overcome at a regional level.

* Corresponding author. Mailing address: Department of Surgery, Box 2926, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-5278. Fax: (919) 684-4288. E-mail: monte{at}duke.edu.

Journal of Virology, March 2002, p. 2233-2244, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2233-2244.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Song, L., Sun, Z.-Y. J., Coleman, K. E., Zwick, M. B., Gach, J. S., Wang, J.-h., Reinherz, E. L., Wagner, G., Kim, M. (2009). Broadly neutralizing anti-HIV-1 antibodies disrupt a hinge-related function of gp41 at the membrane interface. Proc. Natl. Acad. Sci. USA 106: 9057-9062 [Abstract] [Full Text]  
  • Chen, H., Xu, X., Lin, H.-H., Chen, S.-H., Forsman, A., Aasa-Chapman, M., Jones, I. M. (2008). Mapping the immune response to the outer domain of a human immunodeficiency virus-1 clade C gp120. J. Gen. Virol. 89: 2597-2604 [Abstract] [Full Text]  
  • Montero, M., van Houten, N. E., Wang, X., Scott, J. K. (2008). The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design. Microbiol. Mol. Biol. Rev. 72: 54-84 [Abstract] [Full Text]  
  • Moore, P. L., Gray, E. S., Choge, I. A., Ranchobe, N., Mlisana, K., Abdool Karim, S. S., Williamson, C., Morris, L., and the CAPRISA 002 Study Team, (2008). The C3-V4 Region Is a Major Target of Autologous Neutralizing Antibodies in Human Immunodeficiency Virus Type 1 Subtype C Infection. J. Virol. 82: 1860-1869 [Abstract] [Full Text]  
  • Gray, E. S., Moore, P. L., Pantophlet, R. A., Morris, L. (2007). N-Linked Glycan Modifications in gp120 of Human Immunodeficiency Virus Type 1 Subtype C Render Partial Sensitivity to 2G12 Antibody Neutralization. J. Virol. 81: 10769-10776 [Abstract] [Full Text]  
  • Manrique, A., Rusert, P., Joos, B., Fischer, M., Kuster, H., Leemann, C., Niederost, B., Weber, R., Stiegler, G., Katinger, H., Gunthard, H. F., Trkola, A. (2007). In Vivo and In Vitro Escape from Neutralizing Antibodies 2G12, 2F5, and 4E10. J. Virol. 81: 8793-8808 [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]  
  • 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]  
  • Li, B., Decker, J. M., Johnson, R. W., Bibollet-Ruche, F., Wei, X., Mulenga, J., Allen, S., Hunter, E., Hahn, B. H., Shaw, G. M., Blackwell, J. L., Derdeyn, C. A. (2006). Evidence for potent autologous neutralizing antibody titers and compact envelopes in early infection with subtype C human immunodeficiency virus type 1.. J. Virol. 80: 5211-5218 [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]  
  • Seaman, M. S., Xu, L., Beaudry, K., Martin, K. L., Beddall, M. H., Miura, A., Sambor, A., Chakrabarti, B. K., Huang, Y., Bailer, R., Koup, R. A., Mascola, J. R., Nabel, G. J., Letvin, N. L. (2005). Multiclade Human Immunodeficiency Virus Type 1 Envelope Immunogens Elicit Broad Cellular and Humoral Immunity in Rhesus Monkeys. J. Virol. 79: 2956-2963 [Abstract] [Full Text]  
  • Krachmarov, C., Pinter, A., Honnen, W. J., Gorny, M. K., Nyambi, P. N., Zolla-Pazner, S., Kayman, S. C. (2005). Antibodies That Are Cross-Reactive for Human Immunodeficiency Virus Type 1 Clade A and Clade B V3 Domains Are Common in Patient Sera from Cameroon, but Their Neutralization Activity Is Usually Restricted by Epitope Masking. J. Virol. 79: 780-790 [Abstract] [Full Text]  
  • Gao, F., Weaver, E. A., Lu, Z., Li, Y., Liao, H.-X., Ma, B., Alam, S. M., Scearce, R. M., Sutherland, L. L., Yu, J.-S., Decker, J. M., Shaw, G. M., Montefiori, D. C., Korber, B. T., Hahn, B. H., Haynes, B. F. (2005). Antigenicity and Immunogenicity of a Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein. J. Virol. 79: 1154-1163 [Abstract] [Full Text]  
  • Binley, J. M., Wrin, T., Korber, B., Zwick, M. B., Wang, M., Chappey, C., Stiegler, G., Kunert, R., Zolla-Pazner, S., Katinger, H., Petropoulos, C. J., Burton, D. R. (2004). Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies. J. Virol. 78: 13232-13252 [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]  
  • Zwick, M. B., Parren, P. W. H. I., Saphire, E. O., Church, S., Wang, M., Scott, J. K., Dawson, P. E., Wilson, I. A., Burton, D. R. (2003). Molecular Features of the Broadly Neutralizing Immunoglobulin G1 b12 Required for Recognition of Human Immunodeficiency Virus Type 1 gp120. J. Virol. 77: 5863-5876 [Abstract] [Full Text]  
  • Vinner, L., Wee, E. G.-T., Patel, S., Corbet, S., Gao, G. P., Nielsen, C., Wilson, J. M., Ertl, H. C. J., Hanke, T., Fomsgaard, A. (2003). Immunogenicity in Mamu-A*01 rhesus macaques of a CCR5-tropic human immunodeficiency virus type 1 envelope from the primary isolate (Bx08) after synthetic DNA prime and recombinant adenovirus 5 boost. J. Gen. Virol. 84: 203-213 [Abstract] [Full Text]  
  • Sanders, R. W., Venturi, M., Schiffner, L., Kalyanaraman, R., Katinger, H., Lloyd, K. O., Kwong, P. D., Moore, J. P. (2002). The Mannose-Dependent Epitope for Neutralizing Antibody 2G12 on Human Immunodeficiency Virus Type 1 Glycoprotein gp120. J. Virol. 76: 7293-7305 [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»