Document 0809
 DOCN  M94B0809
 TI    Novel mutation (V75T) in human immunodeficiency virus type 1 reverse
       transcriptase confers resistance to
       2',3'-didehydro-2',3'-dideoxythymidine in cell culture.
 DT    9412
 AU    Lacey SF; Larder BA; Antiviral Therapeutic Research Unit, Wellcome
       Research; Laboratories, Beckenham, United Kingdom.
 SO    Antimicrob Agents Chemother. 1994 Jun;38(6):1428-32. Unique Identifier :
       AIDSLINE MED/94379807
 AB    We have selected a human immunodeficiency virus type 1 (HIV-1) mutant
       strain with a moderate (sevenfold) level of resistance to the nucleoside
       analog 2',3'-didehydro-2',3'-dideoxythymidine (D4T or stavudine). After
       serial passage of the HXB2 strain of HIV-1 in MT4 cells, a novel
       mutation involving two nucleotide substitutions in codon 75 of the viral
       reverse transcriptase, altering valine to threonine, was seen. When
       introduced into a wild-type HIV-1 background by site-directed
       mutagenesis, the T-75 mutation conferred cross-resistance to the
       dideoxynucleosides dideoxyinosine and dideoxycytosine as well as to
       2',3'-didehydro-2',3'-dideoxycytosine.
 DE    Base Sequence  Cells, Cultured  Drug Resistance, Microbial  Hela Cells
       Human  HIV-1/*DRUG EFFECTS/ENZYMOLOGY/GENETICS  Molecular Sequence Data
       *Mutation  Reverse Transcriptase/ANTAGONISTS & INHIB/*GENETICS
       Stavudine/*PHARMACOLOGY  Zalcitabine/ANALOGS & DERIVATIVES/PHARMACOLOGY
       Zidovudine/PHARMACOLOGY  JOURNAL ARTICLE

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