       Document 1204
 DOCN  M9591204
 TI    [Molecular basis and clinical significance of HIV-1 resistance to
       nucleoside compounds]
 DT    9509
 AU    Wainberg MA; Gu Z; Salomon H; Arts EJ; Kleiman L; Parniak MA; Morin N;
       Centre SIDA de l'Universite McGill, Institut Lady Davis-Hopital; general
       juif, Montreal, Quebec, Canada.
 SO    C R Acad Sci III. 1995 Mar;318(3):315-28. Unique Identifier : AIDSLINE
       MED/95308297
 AB    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.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY  Drug Resistance,
       Multiple  English Abstract  Genotype  HIV-1/*DRUG
       EFFECTS/ENZYMOLOGY/GENETICS  Human  Mutation  Nucleosides/*PHARMACOLOGY
       Reverse Transcriptase/GENETICS/METABOLISM  Support, Non-U.S. Gov't
       JOURNAL ARTICLE  REVIEW  REVIEW, ACADEMIC

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

