Sulfated Polysaccharides as Potent Inhibitors of HIV-Induced Syncytium Formation

Multinucleated giant cell (syncytium) formation induced by the interaction between the gpl20 glycoprotein expressed on the surface of cells infected with human immunodeficiency virus type 1 (HIV-1) and the CD4 receptor of uninfected CD4-positive (CD4+ ) cells may play an important role in the depletion of T4 lymphocytes in acquired immune deficiency syndrome (AIDS) patients. Using a double fluorescence cell-staining technique and analysis of the cells by the fluorescence-activated cell sorter (FACS), we have demonstrated that giant cell formation between persistently HIV-1-infected HUT-78 cells and uninfected MOLT-4 cells results in a selective destruction of the uninfected CD4+ MOLT-4 cells. Apparently, bystander CD4+ cells may serve as targets for the killing effect of the HIV-1-infected cells, and this killing effect is preceded by fusion between the target (uninfected) and aggressor (infected) cells. Pentosan polysulfate, dextran sulfate, and various other sulfated polysaccharides, but not heparin, have proved to inhibit this cell fusion process and hence protect the target CD4+ cells against destruction by the killer HIV-1-infected cells. Azidothymidine does not interfere with this process. Assuming that fusion between HIV-infected and uninfected CD4+ cells is a crucial event in the pathogenesis of AIDS, any compounds that specifically interfere with this process may be therapeutically advantageous in the treatment of this disease.