An anti-human immunodeficiency virus multiple antigen peptide encompassing the cleavage region of the env precursor interferes with membrane fusion at a post-CD4 binding step.
CLIV is a multiple antigen peptide ([PTKAKRRVVQREKR](4)-K(2)-K-betaA) that encompasses the cleavage region of the human immunodeficiency virus type 1 (HIV-1) envelope precursor. It displays an antiviral activity against HIV-1 and HIV-2 and inhibits HIV-1 Env-mediated cell-to-cell fusion. This effect has previously been attributed to interference with Env processing, resulting in the expression of a nonfusogenic envelope [Virology (1998) 247, 137]. However, we show here that CLIV does not alter the status of Env cleavage at steady state. Using various aggregation/syncytium assays that allow us to discriminate between gp120/CD4 binding and binding followed by gp41-mediated fusion, we demonstrate that CLIV inhibits a step of the cell-to-cell fusion process after CD4 binding. We demonstrate also that CLIV binds at 37 degrees C to a single class of protein present at the CD4(+) cell surface (Scatchard analysis: K(d) = 8 nM; B(max) = 10(4) sites/cell) and that the fusion inhibition activity seems to correlate with binding to this proteic component. In contrast, CLIV interacts with neither membrane-inserted nor CD4-associated Env. We therefore propose that CLIV interferes after Env/CD4 binding with a step of the membrane fusion process that may involve the C-terminal domain of gp120.
Barbouche
R
R
CNRS, Faculté de Médecine Nord, Marseille, France.
Decroly
E
E
Kieny
M P
MP
Fenouillet
E
E
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015686:Gene Products, env / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D005822:Genetic Vectors / Q000235:genetics; D015726:Giant Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D015488:HIV Antigens / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D015498:HIV-2 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008561:Membrane Fusion / Q000187:drug effects*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014616:Vaccinia virus / Q000235:genetics
D019380:Anti-HIV Agents; D015704:CD4 Antigens; C411806:CLIV peptide; D015686:Gene Products, env; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments