Maleylated human serum albumin inhibits HIV-1 infection in vitro.

Abstract

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.

• Authors: M Takami, T Sone, K Mizumoto, K Kino, H Tsunoo
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1180 Issue 2 Pg. 180-6 (Dec 10 1992) ISSN: 0006-3002 [Print] Netherlands
• PMID: 1281431 (Publication Type: Journal Article)

Chemical References

• Maleates
• Polysaccharides
• Serum Albumin
• maleylated serum albumin, human
• Carrageenan
• Dextran Sulfate
• fucoidan
• HIV Reverse Transcriptase
• RNA-Directed DNA Polymerase
• Serum Albumin, Human

Topics

• Acquired Immunodeficiency Syndrome (prevention & control)
• Binding Sites
• CD4-Positive T-Lymphocytes (drug effects, metabolism, microbiology)
• Carrageenan (pharmacology)
• Cell Fusion (drug effects)
• Cell Line (drug effects)
• Dextran Sulfate (pharmacology)
• HIV Reverse Transcriptase
• HIV-1 (drug effects, enzymology, physiology)
• Humans
• Maleates (antagonists & inhibitors, metabolism, pharmacology)
• Polysaccharides (pharmacology)
• RNA-Directed DNA Polymerase (metabolism)
• Serum Albumin (antagonists & inhibitors, metabolism, pharmacology)
• Serum Albumin, Human