Anti-human immunodeficiency virus effects of dextran sulfate are strain dependent and synergistic or antagonistic when dextran sulfate is given in combination with dideoxynucleosides

101

Polysulfates are highly potent and selective inhibitors of the in vitro replication of HIV and other enveloped viruses. They not only inhibit the cytopathic effect of HIV, but also prevent HIV-induced syncytium (giant cell) formation. They also act synergistically with other anti-HIV drugs. The anti-HIV activity of polysulfates is a result of their shielding of the positively charged sites in the V3 loop of the viral envelope glycoprotein gp120. When polysulfates were administered intravenously to rabbits, their half-life was approximately 2h. Although they are very poorly absorbed following oral administration, they can be made orally bioavailable with the appropriate chemical modifications. Also, polysulfates may lose (much of) their anticoagulant activity upon chemical modification without giving up their anti-HIV activity. Their efficacy in the therapy and/or prophylaxis of retroviral infections remains to be demonstrated both in animal models and in humans.

Section: In Vitro Anti-hiv Activity Of Polysulfates In Combination Wisupporting

confidence: 65%

Antiviral Portrait Series: 4. Polysuifates as Inhibitors of HIV and Other Enveloped Viruses

Witvrouw¹,

Desmyter²,

Clercq

1994

101

“…It has been described that the susceptibility to the antiviral effects of dextran sulphate varies among different HIV isolates and strains (Busso et al, 1990;Witvrouw et aI., 1990Witvrouw et aI., , 1991. These findings can be extended to other polyanionic compounds and most probably reflect differences in the interaction of these polyanions with the HIV envelope glycoproteins.…”

Section: Discussionmentioning

confidence: 99%

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

Schols

Pauwels

Witvrouw

et al. 1992

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.

“…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).…”

Section: Discussionmentioning

confidence: 53%

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

Konopka

Davis

Larsen

et al. 1993

Immunodeficiency viruses undergo fusion with liposomes containing anionic phospholipids (Larsen etal., 1990). We have investigated the effect of liposomes composed of cardiolipin, phosphatidylserine or phosphatidylinositol, on the infectivity of three strains of HIV-1 in A3.01 and H9 cells, measured by p24 (gag) production in the medium. The infectivity of HIV-1 in A3.01 or H9 cells was inhibited by the presence of cardiolipin liposomes during a 2 h infection period, with IC50's of 23.0, 4.8, and 5.0 μM phospholipid, respectively, for the different strains. Liposomes composed of phosphatidylserine or phosphatidylinositol were ineffective under similar conditions. However, prolonged pre-incubation of the virus with these liposomes also inhibited infectivity. Inhibition of virus binding to cells could not account for the inhibition of infectivity. We propose that the fusion products of HIV-1 and anionic liposomes are impaired in their ability to fuse with the plasma membrane.