Abstract
The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels and enhances the process of virion budding and release. Mutagenesis studies have shown that the N-terminal transmembrane domain primarily controls both of these activities. Here we report that the Vpu ion channel is inhibited by the amiloride derivatives 5-(N,N-hexamethylene)amiloride and 5-(N,N-dimethyl)amiloride but not by amiloride itself, nor by amantadine. Hexamethyleneamiloride also inhibits budding of virus-like particles from HeLa cells expressing HIV-1 Gag and Vpu proteins. These results confirm the link between Vpu ion channel activity and the budding process and also suggest that amiloride derivatives might have useful anti-HIV-1 properties.
MeSH terms
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Amiloride / analogs & derivatives*
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Amiloride / pharmacology
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Amino Acid Sequence
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Anti-HIV Agents / pharmacology*
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Base Sequence
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Biophysical Phenomena
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Biophysics
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DNA, Viral / genetics
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HIV-1 / drug effects*
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HIV-1 / genetics
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HIV-1 / growth & development
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HIV-1 / physiology*
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HeLa Cells
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Human Immunodeficiency Virus Proteins
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Humans
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Ion Channels / antagonists & inhibitors*
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Ion Channels / metabolism
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Microscopy, Electron
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Molecular Sequence Data
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Viral Regulatory and Accessory Proteins / antagonists & inhibitors*
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Viral Regulatory and Accessory Proteins / genetics
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Viral Regulatory and Accessory Proteins / physiology
Substances
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Anti-HIV Agents
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DNA, Viral
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Human Immunodeficiency Virus Proteins
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Ion Channels
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Peptide Fragments
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Recombinant Proteins
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Viral Regulatory and Accessory Proteins
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vpu protein, Human immunodeficiency virus 1
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5-(N,N-hexamethylene)amiloride
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5-dimethylamiloride
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Amiloride