title: [Molecular basis and clinical significance of HIV-1 resistance to nucleoside compounds].
abstract: The prolonged use of anti-viral nucleosides (ZDV, ddI, ddC) in HIV-infected patients has given rise to the isolation of viral variants that display resistance against these compounds. Tissue culture selection experiments, involving increasing concentrations of anti-viral compounds, have likewise been shown to select for drug-resistant strains of HIV. Cloning, sequencing and site-directed mutagenesis have shown that a series of point mutations in the viral reverse transcriptase (RT) are responsible for this phenomenon. A different series of mutations in RT are responsible for resistance against non-nucleoside inhibitors of this enzyme. These mutations are due to the error-prone nature of RT during viral replication. Mutated forms of recombinant RT, that derive from drug-resistant viruses, have reduced affinity for relevant triphosphorylated nucleosides.
authors.affiliation: Centre SIDA de l'Université McGill, Institut Lady Davis-Hôpital général juif, Montréal, Québec, Canada.
authors.forename: M A
authors.initials: MA
authors.lastname: Wainberg
authors.forename: Z
authors.initials: Z
authors.lastname: Gu
authors.forename: H
authors.initials: H
authors.lastname: Salomon
authors.forename: E J
authors.initials: EJ
authors.lastname: Arts
authors.forename: L
authors.initials: L
authors.lastname: Kleiman
authors.forename: M A
authors.initials: MA
authors.lastname: Parniak
authors.forename: N
authors.initials: N
authors.lastname: Morin
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D018432:Drug Resistance, Multiple; D005838:Genotype; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D009154:Mutation; D009705:Nucleosides / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism
chemical_list: D009705:Nucleosides; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase