INHIBITION OF HIV TYPE-1 PRODUCTION BY HYGROMYCIN-B

HIV infection alters the cellular uptake of ions and other small molec ules. This study was designed to determine whether hygromycin B, a low molecular weight (MW 527) aminoglycoside protein synthesis inhibitor that is normally impermeable to mammalian cells at micromolar concentr ations, can selectively inhibit HIV expression and cytopathology, CD4( +) T lymphoblastoid cells (H9) and peripheral blood mononuclear cells (PBMCs) were infected with HIV-1, then incubated in medium containing various concentrations of hygromycin B, HIV-1-induced formation of mul tinucleated giant cells and single cell killing were dramatically redu ced in the presence of micromolar concentrations of hygromycin B, Hygr omycin B also inhibited HIV-1 production in a dose-dependent manner du ring acute infection, G418, a larger and more hydrophobic aminoglycosi de (MW 692), did not display the same selective inhibition of HIV-1 pr oduction as hygromycin B, Relative to mock-infected cells, protein syn thesis in acutely infected H9 cells was selectively inhibited by hygro mycin B, Hygromycin B also reduced HIV production in PBMCs and in H9 c ells persistently infected with HIV, PCR analysis demonstrated that hy gromycin B did not inhibit HIV-1 reverse transcription, These results demonstrate that HIV-1 infection renders cells more sensitive to hygro mycin B than uninfected cells, and provides support for the hypothesis that HIV-1 induces an alteration of plasma membrane permeability. The HIV-modified cell membrane may be a potential target for antiviral in tervention and chemotherapy.