Document 0001
 DOCN  M95A0001
 TI    Sensitivity/resistance profile of a simian immunodeficiency virus
       containing the reverse transcriptase gene of human immunodeficiency
       virus type 1 (HIV-1) toward the HIV-1-specific non-nucleoside reverse
       transcriptase inhibitors.
 DT    9510
 AU    Balzarini J; Weeger M; Camarasa MJ; De Clercq E; Uberla K; Rega
       Institute for Medical Research, Katholieke Universiteit; Leuven,
       Belgium.
 SO    Biochem Biophys Res Commun. 1995 Jun 26;211(3):850-6. Unique Identifier
       : AIDSLINE MED/95321948
 AB    To develop an animal model for the therapy of AIDS with human
       immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase
       (RT) inhibitors, we recently constructed a hybrid simian
       immunodeficiency virus (SIV)/HIV-1 in which the RT gene of SIV was
       replaced by the RT gene of HIV-1. This chimaeric virus, designated
       RT-SHIV, was found to be markedly sensitive to the inhibitory effects of
       both nucleoside (ddN) and non-nucleoside RT inhibitors (NNRTIs). In
       contrast, SIV was inhibited only by ddNs (i.e., 3TC and AZT), but not
       NNRTIs. When RT-SHIV was grown in the presence of 3TC, nevirapine,
       TSAO-m3T or the thiocarboxanilide UC-42 drug-resistant mutant virus
       strains emerged in cell culture as rapid as for HIV-1(IIIB). The
       antiviral sensitivity/resistance spectrum of the mutant RT-SHIV strains
       against NNRTIs and ddNs, and the nature of the mutations that appeared
       in their RT were similar to those of the mutant HIV-1 strains that were
       selected under identical experimental conditions. Infection of macaques
       with RT-SHIV may be a useful tool for studying the mechanism of
       NNRTI-resistance development and the therapy of NNRTI-resistant viruses
       in an animal model.
 DE    Acquired Immunodeficiency Syndrome/DRUG THERAPY  Antiviral
       Agents/*PHARMACOLOGY  Base Sequence  Comparative Study  Disease Models,
       Animal  Dose-Response Relationship, Drug  Drug Resistance, Microbial
       Drug Screening/*METHODS  HIV-1/ENZYMOLOGY/*GENETICS  Microbial
       Sensitivity Tests/*METHODS  Molecular Sequence Data  Mutation
       Recombinant Proteins/DRUG EFFECTS  Reverse Transcriptase/*ANTAGONISTS &
       INHIB/GENETICS  Support, Non-U.S. Gov't  SIV/DRUG EFFECTS/GENETICS
       JOURNAL ARTICLE

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