INFECTION BY HIV-1 BLOCKED BY BINDING OF DEXTRIN 2-SULFATE TO THE CELL-SURFACE OF ACTIVATED HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS AND CULTURED T-CELLS

1 Structural analogues of a sulphated polysaccharide, dextrin sulphate, were synthesized and tested for their ability to block infection by HIV-1. Using the T-cell lines, C8166 and HPB-ALL, and the laboratory adapted strains of HIV-1.MN, HIV-1.IIIb and HIV-1.RF, dextrin 2-sulphate (D2S) combined the best combination of high anti-HIV-1 activity (95% inhibitory concentration (IC95) = 230 nM) and low anticoagulant activity. It also blocked infection of activated peripheral blood mononuclear (PBMN) cells by five primary viral isolates at an IC95, of 230- 3700 nM depending upon the primary viral isolate tested. 2 In saturation binding studies, [H-3]-D2S bound to a cell surface protein on HPB-ALL cells in a specific and saturable manner with a K-d of 82 +/- 14 nM and a B-max of 4.8 +/- 0.3 pmol/10(6) cells. It bound to other human T-cell lines in a similar manner. 3 There was very little binding of [H-3]-D2S to freshly isolated PBMN cells (B-max 0.18 +/- 0.03 pmol/10(6) cells) and these cells could not be infected by HIV-1. Culture of PBMN cells in lymphocyte growth medium (LGM) containing IL-2 did not significantly change the B-max of[H-3]-D2S. In contrast, PBMN cells which had been cultured with phytohaemagglutinin (PHA; 5 mu ml(-1)) for 72 h had a B-max of [H-3]-D2S binding of 7.2 +/- 0.1 pmol/10(6) cells and these cells could be infected by HIV-1. Removal of the PHA and further culture of the PBMN cells in LGM containing IL-2 resulted in a fall in the B-max to 2.0 +/- 0.1 pmol/10(6) cells. The K-d Of binding did not change significantly during the course of these experiments. 4 [H-3]-D2S did not bind to freshly isolated erythrocytes or to erythrocytes which had been cultured in PHA for 72 h. 5 These results suggest that there is a relationship between the expression of the [H-3]-D2S binding protein on the plasma membrane of PBMN cells and the susceptibility of these cells to infection by HIV-1.