Inhibition of HIV type 1 production by hygromycin B.
HIV infection alters the cellular uptake of ions and other small molecules. 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 concentrations, 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 multinucleated giant cells and single cell killing were dramatically reduced in the presence of micromolar concentrations of hygromycin B. Hygromycin B also inhibited HIV-1 production in a dose-dependent manner during acute infection. G418, a larger and more hydrophobic aminoglycoside (MW 692), did not display the same selective inhibition of HIV-1 production as hygromycin B. Relative to mock-infected cells, protein synthesis in acutely infected H9 cells was selectively inhibited by hygromycin B. Hygromycin B also reduced HIV production in PBMCs and in H9 cells persistently infected with HIV. PCR analysis demonstrated that hygromycin B did not inhibit HIV-1 reverse transcription. These results demonstrate that HIV-1 infection renders cells more sensitive to hygromycin 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 intervention and chemotherapy.
Department of Microbiology and Immunology, Tulane Medical School, New Orleans, Louisiana 70112, USA.
P J
PJ
Gatti
B
B
Choi
A M
AM
Haislip
C D
CD
Fermin
R F
RF
Garry
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004279:DNA, Viral / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D006921:Hygromycin B / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D004279:DNA, Viral; D011500:Protein Synthesis Inhibitors; D006921:Hygromycin B