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PMID: 11836401 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regional clustering of shared neutralization determinants on primary isolates of clade C human immunodeficiency virus type 1 from South Africa.

Journal of virology ·Vol. 76 ·No. 5 ·2002-03-00 ·Pages 2233-44

Bures R, Morris L, Williamson C, Ramjee G, Deers M, Fiscus SA, Abdool-Karim S, Montefiori DC

Abstract

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.

MeSH Terms
Amino Acid Sequence Antibodies, Monoclonal/blood,immunology Female HIV Antibodies/blood,immunology HIV Envelope Protein gp120/genetics,immunology HIV Infections/immunology,virology HIV-1/classification,immunology Humans Molecular Sequence Data Neutralization Tests Peptide Fragments/genetics,immunology Sequence Analysis, DNA Sex Work South Africa
Chemicals
Antibodies, Monoclonal HIV Antibodies HIV Envelope Protein gp120 HIV envelope protein gp120 (305-321) Peptide Fragments
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Bures Renata
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Morris Lynn
Williamson Carolyn
Ramjee Gita
Deers Mark
Fiscus Susan A
Abdool-Karim Salim
Montefiori David C
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.76.5.2233-2244.2002
Published
2002-03-00
Pages
2233-44
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC135941
Subset
IM
Grants
NICHD NIH HHS · P30-HD 37260 · United States
NIDDK NIH HHS · R37 DK049381 · United States
NIAID NIH HHS · AI 46705 · United States
NIDDK NIH HHS · R01 DK049381 · United States
NIDDK NIH HHS · DK 49381 · United States
External Links
PubMed source DOI: 10.1128/jvi.76.5.2233-2244.2002 PMC Full Text View journal details
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