ANTIVIRAL ACTIVITY OF DERIVATIZED DEXTRANS ON HIV-1 INFECTION OF PRIMARY MACROPHAGES AND BLOOD-LYMPHOCYTES

The present study demonstrates at the molecular level that dextran der ivatives carboxymethyl dextran benzylamine (CMDB) and carboxymethyl de xtran benzylamine sulfonate (CMDBS), characterized by a statistical di stribution of anionic carboxylic groups, hydrophobic benzylamide units , and/or sulfonate moieties, interact with HIV-1 LAI gp120 and V3 cons ensus clades B domain. Only limited interaction was observed with carb oxy-methyl dextran (CMD) or dextran (D) under the same conditions. CMD BS and CMDB (1 mu M) strongly inhibited HIV-1 infection of primary mac rophages and primary CD4(+) lymphocytes by macrophage-tropic and T lym phocyte-tropic strains, respectively, while D or CMD had more limited effects on M-tropic infection of primary macrophages and exert no inhi bitory effect on M- or T-tropic infection of primary lymphocytes, CMDB S and CMDB (1 mu M) had limited but significant effect on oligomerized soluble recombinant gp120 binding to primary macrophages while they c learly inhibit (> 50%) such binding to primary lymphocytes. In conclus ion, the inhibitory effect of CMDB and the CMDBS, is observed for HIV M- and T-tropic strain infections of primary lymphocytes and macrophag es which indicates that these compounds interfere with steps of HIV re plicative cycle which neither depend on the virus nor on the cell. (C) 1997 Elsevier Science B.V.