Abstract
Serial passage of human immunodeficiency virus type 1 in MT-2 cells in increasing concentrations of the d- and l-enantiomers of beta-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (d4FC) resulted in the selection of viral variants with reverse transcriptase substitutions M184I or M184V for l-d4FC and I63L, K65R, K70N, K70E, or R172K for d-d4FC. Phenotypic analysis of site-directed mutants defined the role of these mutations in reducing susceptibility to l- or d-d4FC.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Substitution
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Anti-HIV Agents / pharmacology*
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Cell Line
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Cytidine Triphosphate / analogs & derivatives*
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Cytidine Triphosphate / pharmacology
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Drug Resistance, Viral
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HIV Reverse Transcriptase / genetics
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HIV Reverse Transcriptase / metabolism
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HIV-1 / drug effects*
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HIV-1 / enzymology
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HIV-1 / genetics
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Humans
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Mutagenesis, Site-Directed
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Mutation / genetics
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Reverse Transcriptase Inhibitors / pharmacology*
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Stereoisomerism
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Structure-Activity Relationship
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Zalcitabine / analogs & derivatives
Substances
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Anti-HIV Agents
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Reverse Transcriptase Inhibitors
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Cytidine Triphosphate
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Zalcitabine
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HIV Reverse Transcriptase
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dexelvucitabine