Document Detail


Factors determining the breadth and potency of neutralization by V3-specific human monoclonal antibodies derived from subjects infected with clade A or clade B strains of human immunodeficiency virus type 1.
MedLine Citation:
PMID:  16809318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The neutralizing activities of anti-V3 antibodies for HIV-1 isolates is affected both by sequence variation within V3 and by epitope masking by the V1/V2 domain. To analyze the relative contribution of V3 sequence variation, chimeric Env genes that contained consensus V3 sequences from seven HIV-1 subtypes in the neutralization-sensitive SF162 Env backbone were constructed. Resulting viral pseudotypes were tested for neutralization by 15 anti-V3 MAbs isolated from humans infected with viruses of either subtype B (anti-V3(B) MAbs) or subtype A (anti-V3(A) MAbs). Pseudovirions with the subtype B consensus V3 sequence were potently neutralized (IC(50) < 0.006 microg/ml) by all but one of these MAbs, while pseudovirions with V3 subtypes A, C, F, H, AG, and AE were generally neutralized more effectively by anti-V3(A) MAbs than by anti-V3(B) MAbs. A V1/V2-masked Env version of SF162 Env with the consensus B V3 sequence was also neutralized by these MAbs, although with considerably lower potency, while similarly masked chimeras with V3 sequences of subtype A, C, or AG were weakly neutralized by anti-V3(A) MAbs but not by anti-V3(B) MAbs. Mutations in the V1/V2 domain of YU-2 Env increased the sensitivity of this highly resistant Env to a pool of anti-V3(B) MAbs several thousand-fold. These results demonstrated (i) the exceptional sensitivity of representative V3 domains of multiple subtypes to neutralization in the absence of epitope masking, (ii) the broader neutralizing activity of anti-V3(A) MAbs for viruses containing diverse V3 sequences, and (iii) the generality and dominant effect of V1/V2 masking on restriction of V3-mediated neutralization.
Authors:
C P Krachmarov; W J Honnen; S C Kayman; M K Gorny; S Zolla-Pazner; Abraham Pinter
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  80     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-30     Completed Date:  2006-08-30     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7127-35     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / genetics,  immunology*
Antibodies, Viral / genetics,  immunology*
Antibody Specificity / genetics,  immunology*
Epitopes / genetics,  immunology*
Female
Gene Products, env / genetics,  immunology*
HIV-1 / genetics,  immunology*
Humans
Male
Mutation
Protein Structure, Tertiary / genetics
Species Specificity
Virion / genetics,  immunology
Grant Support
ID/Acronym/Agency:
AI27742/AI/NIAID NIH HHS; AI36085/AI/NIAID NIH HHS; AI46283/AI/NIAID NIH HHS; AI47053/AI/NIAID NIH HHS; AI50452/AI/NIAID NIH HHS; HL59725/HL/NHLBI NIH HHS; R01 AI036085/AI/NIAID NIH HHS; R01 HL059725/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Viral; 0/Epitopes; 0/Gene Products, env
Comments/Corrections

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