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M9630107.TXT
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1996-02-27
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Document 0107
DOCN M9630107
TI Quantitative analysis of serum neutralization of human immunodeficiency
virus type 1 from subtypes A, B, C, D, E, F, and I: lack of direct
correlation between neutralization serotypes and genetic subtypes and
evidence for prevalent serum-dependent infectivity enhancement.
DT 9603
AU Kostrikis LG; Cao Y; Ngai H; Moore JP; Ho DD; Aaron Diamond AIDS
Research Center, New York University School of; Medicine, New York
10016, USA.
SO J Virol. 1996 Jan;70(1):445-58. Unique Identifier : AIDSLINE
MED/96099459
AB Human immunodeficiency virus type 1 (HIV-1) M group strains have been
assigned to date to nine distinct genetic subtypes, designated A through
I, according to phylogenetic analyses of nucleotide sequences of their
env or gag genes. Whether there is any relationship between phylogenetic
subtypes and the neutralization serotypes is not clear, yet defining the
nature of any such relationship by mathematical means would be of major
importance for the development of globally effective HIV-1 vaccines. We
have therefore developed a quantitative method to analyze serum
neutralization of HIV-1 isolates and to identify HIV-1 neutralization
serotypes. This method involves calculations of the neutralization
index, N(i), a newly defined parameter derived from plots generated from
in vitro neutralization assays, calculations of pairwise serum-virus
vector distances, and cluster analyses. We have applied this approach to
analyze three independent neutralization matrices involving primary
HIV-1 strains and sera from genetic subtypes A, B, C, D, E, F, and I.
Detailed serum and HIV-1 isolate cluster analyses have shown that in
general, the identified neutralization serotypes do not directly
correlate with HIV-1 genetic subtypes. These results suggest that
neutralization serotypes do not during natural HIV-1 infection are not
governed by antibodies directed against simple epitopes within gp120
monomers. A significant proportion (28%) of 1,213 combinations of sera
and HIV-1 isolates caused serum-dependent infectivity enhancement
[negative N(i) values] rather than neutralization. We also noted that
negative N(i) values tended to correlate better with certain HIV-1
isolates rather than with HIV-1-positive sera. Syncytium-inducing
variants of HIV-1 were slightly more likely than non-syncytium-inducing
variants to undergo serum-dependent infectivity enhancement, although
the latter variants could clearly be susceptible to enhancement.
DE Amino Acids/IMMUNOLOGY Cluster Analysis Human HIV
Antibodies/IMMUNOLOGY HIV Envelope Protein gp120/IMMUNOLOGY HIV
Infections/BLOOD/*IMMUNOLOGY
HIV-1/CLASSIFICATION/GENETICS/*IMMUNOLOGY/ISOLATION & PURIF
Neutralization Tests Peptide Fragments/IMMUNOLOGY Phylogeny
Serotyping Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S.
JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).