Abstract
Human immunodeficiency virus type 1 (HIV-1) replication is shown to be sensitive to the intracellular concentration of deoxynucleoside triphosphate substrates. Addition of thymidine to established cell lines resulted in a dramatic reduction of virus production. The effect could be substantially alleviated by addition of deoxycytidine, which, alone, enhanced viral titers by a factor of 2 to 3. Hydroxyurea treatment abolished HIV-1 replication in peripheral blood mononuclear cells and could be reversed by deoxyadenosine. These data show that HIV-1 replication occurs under suboptimal DNA precursor conditions.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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CD4 Antigens / metabolism
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Cells, Cultured
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Deoxyadenine Nucleotides / metabolism
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Deoxycytidine / pharmacology*
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Deoxycytosine Nucleotides / metabolism
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Deoxyguanine Nucleotides / metabolism
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HIV-1 / drug effects
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HIV-1 / growth & development*
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Humans
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Proviruses / genetics
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Thymidine / pharmacology*
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Thymine Nucleotides / metabolism
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Transcription, Genetic / drug effects
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Virus Replication / drug effects
Substances
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CD4 Antigens
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Deoxyadenine Nucleotides
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Deoxycytosine Nucleotides
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Deoxyguanine Nucleotides
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Thymine Nucleotides
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Deoxycytidine
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2'-deoxycytidine 5'-triphosphate
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deoxyguanosine triphosphate
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thymidine 5'-triphosphate
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Thymidine