Characterization and anti-HIV properties of CD 4-coated red blood cells.
Entry of HIV into its target cells requires its binding to the CD 4 molecule, the HIV receptor. Blocking this initial step of HIV life cycle is a potential target for the design of anti-HIV drugs. Soluble recombinant CD 4 efficiently blocks HIV infection in vitro and is the least toxic anti-HIV drug in humans. However, this molecule has a short half-life in vivo, and poorly neutralizes fresh isolates of HIV-1. Modifications of soluble CD 4 have been constructed, aimed at increasing its half life and other anti-viral properties. We have previously described an efficient method to cross-link soluble CD 4 to human red blood cells. We show here that these cells are uniformly coated as observed by immunofluorescence staining. Each of 8 different anti-CD 4 monoclonal antibodies stained these cells indicating that the epitopes recognized by these antibodies are correctly exposed at the cell membrane. These CD 4-expressing RBC inhibit specifically and in a dose dependent manner the HIV binding to, and infection of, CD 4+ target cells. On a CD 4 molar basis, this inhibition is approximately 15 times more efficient with CD 4-coated red blood cells than with soluble CD 4.
Idziorek
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T
Laboratoire de Biologie et Génétique des Infections Rétrovirales, CNRS URA 1463, Hôpital de la Pitié, Paris, France.
Chams
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V
Klatzmann
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D
D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology*; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007700:Kinetics
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes