Document 0712
 DOCN  M9650712
 TI    Differential role of V3-specific antibodies in neutralization assays
       involving primary and laboratory-adapted isolates of HIV type 1.
 DT    9605
 AU    Vancott TC; Polonis VR; Loomis LD; Michael NL; Nara PL; Birx DL;
       Division of Retrovirology, Walter Reed Army Institute of; Research,
       Rockville, Maryland 20850, USA.
 SO    AIDS Res Hum Retroviruses. 1995 Nov;11(11):1379-91. Unique Identifier :
       AIDSLINE MED/96159136
 AB    To identify epitopes important in neutralizing primary HIV-1 isolates,
       we have selectively depleted HIV-1 sera of antibodies specific for the
       third hypervariable region (V3) of the HIV-1 envelope glycoprotein
       gp120, and then assessed the functional consequences of such depletion
       in neutralization assays. The nucleotide sequence of the V3 loop region
       from HIV-1 PBMC DNA was determined for three HIV-1-infected patients,
       corresponding peptides were synthesized, and then subsequently used for
       V3 depletion of the patient sera. Depletion using a single clade B V3
       peptide was capable of depleting > 98% of binding antibodies to multiple
       clade B V3 peptides, including those with changes within the GPGX tip of
       the loop. Depleted and undepleted sera were studied for their ability to
       neutralize both laboratory-adapted HIV-1MN and two primary HIV-1
       isolates with known V3 sequences, using a viral infectivity reduction
       assay. While the majority of HIV-1MN neutralization was lost on V3
       depletion, the loss in neutralization capacity against primary isolates
       by these same V3-depleted sera was substantially less pronounced. This
       suggests that V3 peptide-specific antibodies within HIV-1 serum play a
       fundamentally different role in mediating neutralization in assays
       involving laboratory-adapted and primary isolates and implicates
       antibodies with epitope specificities outside of V3 as major
       determinants in neutralization assays involving primary isolates.
 DE    Amino Acid Sequence  Base Sequence  Cell Line  DNA, Viral/GENETICS
       Epitopes/IMMUNOLOGY  Human  HIV Antibodies/*IMMUNOLOGY  HIV Envelope
       Protein gp120/CHEMISTRY/GENETICS/*IMMUNOLOGY  HIV
       Infections/*IMMUNOLOGY/VIROLOGY  HIV-1/*IMMUNOLOGY/ISOLATION & PURIF
       Molecular Sequence Data  Neutralization Tests  Peptide
       Fragments/CHEMISTRY/GENETICS/*IMMUNOLOGY  Protein Conformation  JOURNAL
       ARTICLE

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