Maleylated human serum albumin inhibits HIV-1 infection in vitro.
Maleylated-human serum albumin (Mal-HSA) inhibited human immunodeficiency virus type-1 (HIV-1) infection of MT-4 cells in vitro. It was also found to inhibit the fusion between uninfected CD4+ cells (Molt-4 clone 8 cells) and HIV-1 infected cells (Molt-4/HIV-1) to form syncytia. To investigate the mechanism of the inhibition, a study was designed to determine whether Mal-HSA could bind to CD4+ cells. Mal-HSA could bind to both MT-4 cells and Molt-4 clone 8 cells with high affinity, Kd = 2.0 nM and Kd = 5.8 nM, respectively. However, Mal-HSA could neither inhibit anti CD4 antibody Leu 3a binding to Molt-4 clone 8 cells nor modulate the expression of CD4 molecules on the surface of the cells. Mal-HSA binding to Molt-4 clone 8 cells was completely inhibited by sulfated polysaccharides bearing anti-HIV activity, such as dextran sulfate, fucoidan and carrageenan. Other HIV-1 susceptible human T-cell lines, such as Molt-4, CEM-5, H-9 and HuT-78 cells, also have Mal-HSA binding sites showing a high affinity, Kd = 0.9 +/- 0.4 nM. Mal-HSA binding proteins of Molt-4 clone 8 cells were identified by ligand blotting as 155 and 220 kDa proteins. Unlike dextran sulfate, Mal-HSA could not inhibit reverse transcriptase activity of HIV-1. These results indicate that Mal-HSA inhibits HIV-1 infection and syncytia formation, and suggest that 155 and/or 220 kDa proteins of target cells are involved in HIV-1 adsorption and/or the membrane fusion between HIV-1 and target cells.
D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D002351:Carrageenan / Q000494:pharmacology; D002459:Cell Fusion / Q000187:drug effects*; D002460:Cell Line / Q000187:drug effects; D016264:Dextran Sulfate / Q000494:pharmacology; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D008298:Maleates / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D012709:Serum Albumin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000075462:Serum Albumin, Human
D008298:Maleates; D011134:Polysaccharides; D012709:Serum Albumin; C078756:maleylated serum albumin, human; D002351:Carrageenan; D016264:Dextran Sulfate; C007789:fucoidan; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D000075462:Serum Albumin, Human