Inhibitory effect of the oral immune response modifier, bestatin, on cell-mediated and cell-free HIV infection in vitro

The antiviral effect of the immunomodulating anti-cancer agent, bestatin, was examined in vitro by exposing MT-4 lymphocytes to HIV in the presence of 10-fold dilutions of drug (range 100 μg-100 pg/ml). The reduction in infectivity was measured by p24 ELISA and compared to the effect of established anti-HIV drugs-azidothymidine (AZT) and dextran sulfate. The results indicate that low doses of bestatin (1 μg/ml) can completely inhibit viral infection resulting either from inoculation with free virus or coculture with infected lymphocytes. Unlike AZT or dextran sulfate, bestatin prevents HIV infection without interfering with the rate of cell growth. No appreciable decrease in HIV production was observed when chronically infected virus-producing T cell lines ie, H9, MOLT 4, HPB-ALL, 8E5 and MT -2 were treated with bestatin. Bestatin appears to act in the early stages of viral penetration, possibly through inhibition of lymphocyte-associated aminopeptidases.