Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Maleylated human serum albumin inhibits HIV-1 infection in vitro. 128 31

Succinylated human serum albumin (Suc-HSA) was synthesized by treating human serum albumin with succinic anhydride. Among similar proteins and neo(glyco)proteins tested, Suc-HSA exhibits a pronounced net negative charge, a feature that largely contributes to its efficacy against replication of human immunodeficiency virus type 1 (HIV-1). To assess further the antiviral effect of Suc-HSA, the effect on HIV-1 replication was studied in the presence of whole human plasma. Pretreatment of MT2 cells with Suc-HSA was more efficacious than direct Suc-HSA treatment of HIV prior to addition to the cells. No changes in the antiviral effect of Suc-HSA were observed in tissue culture medium, 30% plasma, or whole plasma when CPDA-1 (citrate-phosphate-dextrose-adenine 1) was used as the anticoagulant. However, a dramatic decrease (greater than 99%) in the antiviral activity was observed when these experiments were performed in plasma prepared from blood using heparin as anticoagulant. The antagonistic effect by heparin was observed both in the case that heparin was added prior to or after addition of Suc-HSA to the test system. In the present study we demonstrate that heparin largely reduces Suc-HSA activity on HIV replication in the same concentration in which if affects binding of Suc-HSA to the envelope protein gp120 and in particular its V3 domain. In the same concentration range, heparin reduced binding of Suc-HSA to MT4 cells, another HTLV-I-transformed cell line. It is concluded that heparin can displace Suc-HSA from its binding sites on hybrid lymphoid cells as well as on HIV-1 particles. Therefore, we conclude that both the binding to cells and to virus contribute to the potent anti-HIV-1 effect. The fact that heparin and heparin degradation products antagonize Suc-HSA without having a significant anti-HIV-1 effect indicates that the anticoagulant acts as a relatively weak partial inhibitor.
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PMID:The in vitro anti-HIV efficacy of negatively charged human serum albumin is antagonized by heparin. 916 36

Negatively charged albumins (NCAs) have been identified as potent inhibitors of HIV-1 replication in vitro. Time of addition studies suggest that succinylated and aconitylated human serum albumin (Suc-HSA and Aco-HSA) act at an early stage of the virus life cycle, and surface plasmon resonance (BIAcore) experiments have confirmed a direct interaction of NCAs with HIV-1 gp120. Resistance to Suc-HSA and Aco-HSA was analyzed by characterizing HIV-1 variants that were selected in cell culture after serial passage of the NL4-3 strain in the presence of the compounds. After 24 passages (126 days) we isolated variants that were resistant to Suc-HSA (>27-fold) and Aco-HSA (37-fold), as compared with the wild-type NL4-3 virus. The binding of the NCA-resistant HIV strains to CD4+ MT-4 cells could no longer be inhibited by either Suc- or Aco-HSA. The emergence of mutations in the envelope gp120 of the resistant virus paralleled the emergence of the resistant phenotype. The Suc-HSA-resistant strain was 100-fold cross-resistant to the G quartet-containing oligonucleotide AR177 (Zintevir, an HIV-binding inhibitor), and partially cross-resistant to dextran sulfate, but remained sensitive to the bicyclam AMD3100 and the chemokine SDF-1alpha, which block HIV replication by interaction with the chemokine receptor CXCR4. Furthermore, neither Suc-HSA nor Aco-HSA inhibited the binding of monoclonal antibodies 12G5 and 2D7 (directed to CXCR4 and CCR5, respectively) in SUPT-1 cells or THP-1 cells. These results confirm that NCAs bind primarily to gp120 and do not interact directly with the HIV chemokine receptor but block the binding of the virus particles (through gp120) with CD4+ cells.
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PMID:Resistance of the human immunodeficiency virus to the inhibitory action of negatively charged albumins on virus binding to CD4. 1058 Apr 4