Document 0544
 DOCN  M9650544
 TI    Alanine substitution of two arginines in amino terminus of V3 of SIV
       disrupts CD4 binding whereas a similar replacement of two amino acids,
       lysine and arginine, in the carboxyl half of V3 prevents binding of a
       neutralizing monoclonal antibody.
 DT    9605
 AU    Javaherian K; Zuchowski L; Clark FT; Repligen Corporation, Cambridge,
       Massachusetts 02139, USA.
 SO    AIDS Res Hum Retroviruses. 1995 Sep;11(9):1101-5. Unique Identifier :
       AIDSLINE MED/96089217
 AB    A series of amino acid substitutions were carried out in the V3 loop of
       SIV gp120 to investigate their effects on binding of the envelope to CD4
       and neutralizing monoclonal antibodies. Alanine replacement of two
       adjacent arginines at the amino terminus of V3 resulted in a molecule
       that bound neither sCD4 nor conformation-dependent neutralizing
       monoclonal KK5 and KK9. A similar substitution of two amino acids,
       lysine and arginine, in the carboxyl half of V3 disrupted binding to KK9
       without affecting CD4 binding. Removal of V3 from the envelope gave rise
       to a molecule that was not secreted. These data suggest a close linkage
       between V3 and CD4 binding domains of gp120, although neutralizing
       antibodies directed to V3 do not block binding of gp120 to CD4. We
       propose that differences in the modes of interactions of the V3
       disulfide loops with CD4 in SIV and HIV may be responsible for the
       observed different neutralizing properties of the two V3 loops.
 DE    Amino Acid Sequence  Animal  Antibodies, Monoclonal/METABOLISM
       Antibodies, Viral/METABOLISM  Antigens, CD4/*METABOLISM  Binding Sites
       Cell Line  HIV Envelope Protein gp120/CHEMISTRY/*GENETICS/*IMMUNOLOGY
       Models, Molecular  Molecular Sequence Data  Mutagenesis, Site-Directed
       Neutralization Tests  SIV/*GENETICS/*IMMUNOLOGY  JOURNAL ARTICLE

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