Differential Activity of Polyanionic Compounds and Castanospermine against HIV Replication and HIV-Induced Syncytium Formation Depending on Virus Strain and Cell Type

Abstract

SummaryPolyanionic compounds [i.e. pentosan polysulphate, dextran sulphate, heparin, suramin, and aurintricarboxylic acid (ATA)) and castanospermine were examined for their inhibitory effect on human immunodeficiency virus (HIV) strains (HIV-1 I11B , HIV-1RF, HIV-2 ROD and HIV-2 EHO ) in two different assays (HIV cytopathicity in MT-4 cells and HIV antigen expression in CEM cells). In the MT-4 assay dextran sulphate and pentosan polysulphatewere more active against HIV-2 ROD , suramin was more active against HIV-1 RF , and ATA more active against HIV-2 EHo • Heparin was less, but castanospermine was more, active against the two HIV-2 strains. In the CEM assay dextran sulphate and suramin were equally active against all HIV strains, pentosan polysulphate was more active against both HIV-2 strains, whereas heparin was less active against HIV-2 ROD and ATA again was more active against HIV-2 EHO ' The compounds and soluble CD4 (sCD4)were also tested in the HIV-induced syncytium formation assay, where chronically infected HUT-78 cells were mixed with un infected MOLT-4 or CEM cells. The inhibitoryeffect of suramin and ATA on syncytium formation was independent of the virus strain or cell type. For dextran sulphate and pentosan polysulphate, it was dependent on virus strain, and for heparin, castanospermine, and sCD4, it was dependent on both the virus strain and cell type.

Anionic Liposomes Inhibit Human Immunodeficiency Virus Type 1 (HIV-1) Infectivity in CD4+A3.01 and H9 Cells

“…These findings were not unexpected, since strain specific antiviral effects of dextran sulphate (Busso and Resnick, 1990;Schols et al, 1992) and rsCD4 (Daar et al, 1990) have also been reported. Passage of HIV-1 isolates through various human cell lines can alter the cellular host range tropism (Cheng-Mayer et al, 1991;Peden et al, 1991), because of differences in the cell-type-dependent glycosylation of the same viral envelope protein (Cheng-Mayer et al, 1991).…”

A monoclonal antibody to the gp120-CD4 complex has differential effects on HIV-induced syncytium formation and viral infectivity

“…Thus, the presence of the antibody interferes effectively with an already inefficient process in H9 cells, while it cannot interfere with an efficient fusion reaction in the case of Sup-T1 cells. Similarly, the cell type used markedly affects the anti-HIV activity of polyanionic compounds and glycosylation inhibitors (Schols et al, 1992). Recently, Gershoni et al (1993) have described several MAbs against the CD4/gpl20 complex, some of which inhibit cell-~zell fusion to different degrees; however, their effect on HIV infection was not reported.…”

In vitro Activity of Polyhydroxycarboxylates against Herpesviruses and Hiv

“…The mechanism of action may be attributed to inhibition of the interaction between the viral glycoprotein gp120 and the cellular CD4 receptor. In general, polyanionic compounds exhibit their anti-HIV activity by binding to the V3 domain of gp120 (Baba et al, 1988b;Nakashima et al, 1989;Schols et al, 1991, 1992, Witvrouw et al, 1994. Although the polyanions inhibit the binding of herpesviruses and HIV, and thus indirectly prevent the subsequent fusion process as well, their effects on the replication of influenza virus can be ascribed primarily to inhibition of virus-cell fusion (Lüscher-Mattli & Glück, 1990;Ikeda et al, 1994).…”