ANTI-HIV-1 ACTIVITY OF INORGANIC POLYPHOSPHATES

Human blood plasma, serum, peripheral blood mononuclear cells, and ery throcytes contain significant amounts of inorganic polyphosphates (ran ging from 53 to 116 mu M, in terms of phosphate residues). Here we dem onstrate that at higher concentrations linear polyphosphates display c ytoprotective and antiviral activity. Sodium tetrapolyphosphate and th e longer polymers, with average chain lengths of 15, 34, and 91 phosph ate residues, significantly inhibited human immunodeficiency virus typ e 1 (HIV-1) infection of cells in vitro at concentrations greater than or equal to 33.3 mu g/ml (greater than or equal to 283-324 mu M phosp hate residues), whereas sodium tripolyphosphate was ineffective. In th e tested concentration range, these compounds had no effect on cell gr owth. The longer-chain polyphosphates (polyphosphates with mean chain lengths of 15 and 34) but not sodium tripolyphosphate and sodium tetra polyphosphate also inhibited HIV-1-induced syncytium formation at a co ncentration of 160 mu g/ml (1.51-1.54 mM phosphate residues). The resu lts obtained with the syncytium assay and by cell-virus binding experi ments indicate that the anti-HIV effect of these nontoxic polyanions m ay be caused by binding of the compounds to both the host cell surface and the virus, thereby inhibiting adsorption of the virus. Competitio n experiments revealed that binding of [P-32]polyphosphate to Molt-3 c ells was only partially inhibited by the antibody OKT4A.