Document 0418
 DOCN  M9490418
 TI    Multibranched V3 peptides inhibit human immunodeficiency virus infection
       in human lymphocytes and macrophages.
 DT    9411
 AU    Yahi N; Fantini J; Mabrouk K; Tamalet C; de Micco P; van Rietschoten J;
       Rochat H; Sabatier JM; CNRS URA 1455, Laboratoire de Biochimie,
       Ingenierie de; Proteines, Faculte de Medecine Secteur Nord, Marseille,;
       France.
 SO    J Virol. 1994 Sep;68(9):5714-20. Unique Identifier : AIDSLINE
       MED/94335086
 AB    Synthetic polymeric constructions (SPCs) including the consensus
       sequence of the human immunodeficiency virus type 1 (HIV-1) surface
       envelope glycoprotein gp120 V3 loop (GPGRAF) blocked the fusion between
       HIV-1- and HIV-2-infected cells and CD4+ uninfected cells. A
       structure-activity relationship study using V3 SPC analogs showed that
       the most efficient inhibitor of cell fusion was an eight-branched SPC
       with the hexapeptide motif GPGRAF (i.e., [GPGRAF]8-SPC). N-terminal
       acetylation or incorporation of D-amino acids in the GPGRAF sequence of
       this SPC resulted in significant loss of activity. Analogs with fewer
       than six residues in the motif (i.e., GPGRA or GPGR), as well as SPCs
       with a nonrelevant sequence, did not inhibit cell fusion, demonstrating
       the high specificity of the antifusion activity. [GPGRAF]8-SPC, which
       was not toxic to CEM cells at concentrations of up to 50 microM,
       inhibited 50% of HIV-1(LAI) replication in these cells at a
       concentration of 0.07 microM. Moreover, [GPGRAF]8-SPC inhibited the
       infection of human peripheral blood mononuclear cells by several HIV-1
       and HIV-2 isolates, including laboratory strains [HIV-1(LAI),
       HIV-1(NDK), and HIV-2(ROD)], and fresh primary isolates, including two
       zidovudine-resistant HIV-1 isolates and two HIV-2 isolates obtained from
       infected individuals. The multibranched peptide also inhibited infection
       of human primary macrophages by the highly cytopathic macrophage-tropic
       isolate HIV-1(89.6). The antiviral activity of [GPGRAF]8-SPC was not
       related to a virucidal effect, since preincubation of HIV-1 with the
       peptide did not affect its infectious titer. This result is in agreement
       with the concept that the multibranched peptide mimics a part of the V3
       loop and thus interacts with the host cell. The therapeutic properties
       of synthetic multibranched peptides based on the V3 loop consensus motif
       should be evaluated in HIV-infected patients.
 DE    Amino Acid Sequence  Cell Fusion/DRUG EFFECTS  Human  HIV Envelope
       Protein gp120/CHEMISTRY  HIV Infections/*MICROBIOLOGY  HIV-2/GROWTH &
       DEVELOPMENT  In Vitro  Leukocytes, Mononuclear/MICROBIOLOGY
       Macrophages/MICROBIOLOGY  Molecular Sequence Data  Peptides/CHEMISTRY
       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).