Low L, Parish C, Warren H, Mathijs JM, Kazazi F, Cunningham AL; International Conference on AIDS.
Int Conf AIDS. 1989 Jun 4-9; 5: 528 (abstract no. W.C.O.23).
Virology Unit, Westmead Hospital, Westmead, Sydney
A wide range of sulphated polyanions has been examined for inhibition of HIV infection of MT4 lymphoblastoid cell lines by wild and laboratory strains of HIV, as detected by cytopathic effect and extracellular HIV antigen levels at 6-8 days. The most potent inhibitors were dextran sulphate, polyanethole sulphonate and pentosan sulphate (ID50=10 and 1ug/ml respectively; antiviral index greater than 1000 for all compounds). Fucoidin sulphate, polyvinyl sulphate iota-carrageenan and dextran sulphate 5000 were less potent (ID50+100ug/ml). Potency of these compounds was increased by using serum depleted of polyanion binding proteins in the cell culture medium. Fucoidin sulphate, polyanethole sulphonate polyvinyl sulphate and a dextran sulphate 500,000 (not D.S.5000) inhibited binding of 11/12 anti-CD4 monoclonal antibodies (including anti-OKT4a but not anti OKT4) to T cells. However 20 anti CD8 monoclonal antibodies did not inhibit binding. Therefore a correlation between inhibition of anti OKT4a binding and HIV infection was demonstrated, with the exception of pentosan sulphate and the small dextran sulphate polymer. These anomalies are probably caused by the ability of these smaller polyanions to inhibit binding of large viral particles but not highly specific monoclonal antibodies. In addition, we have not been able to demonstrate binding of radio-labelled partially (lentil lectin) purified native gp120 to dextran sulphate immobilized on fibres. Competition between residual cell glycoproteins and gp120 is most unlikely because of the excess capacity of the polyanion conjugated fibres. Hence these sulphated polysaccharides may bind to basic amino acid residues in the first two domains of CD4, in close apposition to the gp120 binding sites.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Antibodies, Monoclonal
- Antigens, CD4
- Antiviral Agents
- Binding Sites
- Dextran Sulfate
- HIV
- HIV Antibodies
- HIV Antigens
- HIV Envelope Protein gp120
- HIV Infections
- In Vitro
- OKT4A
- Pentosan Sulfuric Polyester
- Polymers
- Polysaccharides
- Sulfates
- Sulfur Oxides
- Sulfuric Acid Esters
- fucoidan
- immunology
- polyanions
Other ID:
UI: 102178630
From Meeting Abstracts