       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).

