Document 0874
 DOCN  M9540874
 TI    Multibranched peptide constructs derived from the V3 loop of envelope
       glycoprotein gp120 inhibit human immunodeficiency virus type 1 infection
       through interaction with CD4.
 DT    9504
 AU    Benjouad A; Chapuis F; Fenouillet E; Gluckman JC; Laboratoire de
       Biologie et Genetique des Pathologies; Immunitaires, CNRS URA 1463,
       Paris, France.
 SO    Virology. 1995 Jan 10;206(1):457-64. Unique Identifier : AIDSLINE
       MED/95133180
 AB    The V3 loop of the gp120 of human immunodeficiency virus type 1 (HIV-1)
       is assumed to be involved in HIV-1-mediated membrane fusion. V3-derived
       peptides have been shown either to enhance or to prevent HIV-1
       infection. Multibranched peptide constructs (MBPCs) derived from the V3
       North American/European consensus sequence were designed to sort out
       these conflicting findings. At 5 microM, MBPC1 (8-branched GPGRAF)
       totally, and MBPC2 ([RKSIHIGPGRAFYT]4) partially, inhibited HIV-1LAI
       infection, whereas the GPGRAF monomer had only a limited effect. A
       peptide of the entire V3 consensus loop and a control MBPC had no
       detectable activity. The 5 microM MBPC1 HIV-1-inhibiting concentration
       was not cytotoxic, nor did it alter T lymphocyte allogeneic, antigen-,
       or mitogen-induced reactivities, and it was about 5- to 50-fold lower
       (MBPC2 and MBPC1, respectively) than that resulting in 50% cell death.
       Analysis of MBPC immunoreactivity showed that MBPC2, but not MBPC1,
       strongly reacted with human HIV-1 positive sera. Only MBPC2 elicited
       significant antibody responses in rabbits. The V3-derived MBPCs bound to
       CD4+ cells, as determined by immunofluorescence analysis. The binding
       was inhibited either by soluble CD4 or by CD4 monoclonal antibody (mAb)
       MT151, which recognizes the CDR3 region of the D1 domain of CD4, but not
       by other CD4 mAbs Leu3a, OKT4A, Q4021, 13B8-2, 5A8, RFT4, nor by the
       CD26 mAb BA5. Therefore, it appears likely that MBPCs inhibit HIV-1
       infection by interacting with the CDR3 region of CD4 or with a region in
       its vicinity.
 DE    Amino Acid Sequence  Animal  Antigens, CD4/*DRUG EFFECTS  Antiviral
       Agents/CHEMISTRY/*PHARMACOLOGY  Cell Division  Cell Line  Cross
       Reactions  Human  HIV Envelope Protein gp120/*PHARMACOLOGY  HIV-1/*DRUG
       EFFECTS/PATHOGENICITY  Lymphocytes/CYTOLOGY  Molecular Sequence Data
       Peptide Fragments/*PHARMACOLOGY
       Peptides/CHEMISTRY/IMMUNOLOGY/*PHARMACOLOGY  Protein Binding  Rabbits
       Support, Non-U.S. Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).