A CD 4: immunoglobulin fusion protein with antiviral effects against HIV.
Antibody-like molecules consisting of the human CD 4 extracellular domain fused to human IgG1 heavy chain constant regions were genetically constructed and expressed in a BHK cell stable transfectant. Purified chimeric antibodies bound to HIV particles as it was shown by immuno electron microscopy, inhibited fusions of HIV-1-infected cells with uninfected cells, neutralized HIV-1, and were able to inhibit the spread of a cellular HIV-1 infection in CD 4+ cells. Plaque reduction assays with CD 4(+)-transfected Hela-cells showed a comparable inhibition of HIV-1 and HIV-2. Inhibitory functions were enhanced in the presence of complement. HIV-1- and HIV-2-infected CD 4+ cells were efficiently lysed by a slow, complement-dependent mechanism, whereas uninfected CD 4+ cells and HLA-DR+ cells were not affected.
Gregersen
J P
JP
Research Laboratories, Behringwerke AG, Marburg, Federal Republic of Germany.
Mehdi
S
S
Gelderblom
H
H
Zettlmeissl
G
G
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology; D015704:CD4 Antigens / Q000494:pharmacology*; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006168:Guinea Pigs; D006678:HIV / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000494:pharmacology*; D007142:Immunoglobulin gamma-Chains; D008264:Macrophages / Q000382:microbiology; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology*; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D015704:CD4 Antigens; C063735:CD4-IgG1 hinge fusion protein, recombinant; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D011993:Recombinant Fusion Proteins; D003165:Complement System Proteins