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Infection by HIV‐1 blocked by binding of dextrin 2‐sulphate to the cell surface of activated human peripheral blood mononuclear cells and cultured T‐cells
Author(s) -
Shaunak Sunil,
Gooderham Nigel J.,
Edwards Robert J.,
Payvandi Nassrin,
Javan Caroline M.,
Baggett Neil,
MacDermot John,
Weber Jonathan N.,
Davies Donald S.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb16187.x
Subject(s) - peripheral blood mononuclear cell , biology , phytohaemagglutinin , cell culture , microbiology and biotechnology , lymphocyte , in vitro , immunology , biochemistry , genetics
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 (IC 95 ) = 230 nM) and low anticoagulant activity. It also blocked infection of activated peripheral blood mononuclear (PBMN) cells by five primary viral isolates at an IC 95 of 230–3700 nM depending upon the primary viral isolate tested. 2 In saturation binding studies, [ 3 H]‐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 [ 3 H]‐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 [ 3 H]‐D2S. In contrast, PBMN cells which had been cultured with phytohaemagglutinin (PHA; 5 μg ml −1 ) for 72 h had a B max of [ 3 H]‐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 [ 3 H]‐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 [ 3 H]‐D2S binding protein on the plasma membrane of PBMN cells and the susceptibility of these cells to infection by HIV‐1.