Inhibition of HIV type 1 production by hygromycin B.

Abstract

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.

• Authors: P J Gatti, B Choi, A M Haislip, C D Fermin, R F Garry
• Journal: AIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 14 Issue 10 Pg. 885-92 (Jul 01 1998) ISSN: 0889-2229 [Print] United States
• PMID: 9671217 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Bacterial Agents
• Anti-HIV Agents
• DNA, Viral
• Protein Synthesis Inhibitors
• Hygromycin B

Topics

• Anti-Bacterial Agents (pharmacology)
• Anti-HIV Agents (pharmacology)
• DNA, Viral (biosynthesis)
• HIV-1 (drug effects, genetics, growth & development, metabolism)
• Humans
• Hygromycin B (pharmacology)
• Protein Biosynthesis
• Protein Synthesis Inhibitors (pharmacology)
• Tumor Cells, Cultured