Abstract
Genotypic surveys suggest that human immunodeficiency virus type 1 (HIV-1) and HIV-2 evolve different sets of mutations in response to nucleoside reverse-transcriptase inhibitors (NRTIs). We used site-directed mutagenesis, culture-based phenotyping, and cell-free assays to determine the resistance profiles conferred by specific amino acid replacements in HIV-2 reverse transcriptase. Although thymidine analogue mutations had no effect on zidovudine sensitivity, the addition of Q151M together with K65R or M184V was sufficient for high-level resistance to both lamivudine and zidovudine in HIV-2, and the combination of K65R, Q151M, and M184V conferred classwide NRTI resistance. These data suggest that current NRTI-based regimens are suboptimal for treating HIV-2 infection.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acquired Immunodeficiency Syndrome / drug therapy*
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Africa, Western / epidemiology
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Amino Acid Substitution
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Anti-HIV Agents / pharmacology
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Antiviral Agents / pharmacology*
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Drug Resistance, Viral / drug effects
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Genetic Predisposition to Disease
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HIV Infections / drug therapy*
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HIV-1 / drug effects
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HIV-1 / genetics
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HIV-2 / drug effects
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HIV-2 / enzymology
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HIV-2 / genetics*
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Humans
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Mutagenesis, Site-Directed
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Phenotype
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RNA-Directed DNA Polymerase / drug effects
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RNA-Directed DNA Polymerase / genetics*
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Reverse Transcriptase Inhibitors / therapeutic use*
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Zidovudine / pharmacology
Substances
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Anti-HIV Agents
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Antiviral Agents
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Reverse Transcriptase Inhibitors
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Zidovudine
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RNA-Directed DNA Polymerase