CURDLAN SULFATE AND HIV-1 .2. INVITRO LONG-TERM TREATMENT OF HIV-1 INFECTION WITH CURDLAN SULFATE

Short-term (1 h) treatment with a newly synthesized sulfated polysaccharide, curdlan sulfate (CRDS), showed relatively weak blocking effects on the binding of human immunodeficiency virus type 1 (HIV-1) to the surface of H9 cells. To investigate whether long-term treatment with CRDS could strengthen this effect, CRDS in various doses (0. 1, 1, 10, and 100-mu-g/ml) was used in 2-week treatment periods in four separate protocols or "Procedures." SF titers and p24 antigen levels were partially suppressed during long-term CRDS treatment but returned to control levels after the treatment was terminated. In addition, no direct cytotoxicity of CRDS to H9 cells or H9/HIV-1 cells was observed in vitro in the course of continuous exposure to 100-mu-g/ml CRDS for 2 weeks. These results demonstrate the effectiveness of long-term treatment of cells infected with HIV-1 in inhibiting virus expression. The most dramatic inhibition results were obtained when the compound was present both at the time of exposure of cells to virus and during a long-term follow-up treatment. These results show that CRDS inhibits both the cell-free and cell-associated transmission of HIV-1 to host cells and interferes with early events in virus infection. In contrast, CRDS exhibits no significant virucidal activity and has little e Tect on already infected cells.