       Document 0211
 DOCN  M9630211
 TI    Clinical isolates of HIV-1 contain few pre-existing proteinase inhibitor
       resistance-conferring mutations.
 DT    9603
 AU    Yamaguchi K; Byrn RA; Division of Hematology/Oncology, Deaconess
       Hospital, Harvard; Medical School, Boston, MA 02215, USA.
 SO    Biochim Biophys Acta. 1995 Dec 6;1253(2):136-40. Unique Identifier :
       AIDSLINE +
 AB    Proteinase inhibitors are an important new class of antiviral agents for
       AIDS, however, in vitro experiments have identified proteinase mutations
       that confer resistance to several different families of the inhibitors.
       This study was undertaken to determine if these resistance-conferring
       amino-acid substitutions occur in HIV strains before the application of
       selective pressure. We determined the nucleic acid sequence of the
       proteinase gene from the 23 clinical isolates of HIV-1 and three
       laboratory-adapted strains using a method that detects the majority
       species present in viral populations. Analysis of minor subpopulations
       will require alternative strategies. The clinical isolates studied
       contained an average of 3 (range 1-8) amino-acid substitutions as
       compared to the prototypical BH10 sequence. We did not detect
       substitutions characteristic of reported highly proteinase-resistant
       strains. These results suggest significant variation occurs in the HIV-1
       proteinase gene but pre-existing highly proteinase-resistant strains are
       uncommon.
 DE    Amino Acid Sequence  Base Sequence  Comparative Study  Drug Resistance,
       Microbial/GENETICS  Human  HIV Protease/*GENETICS  HIV Protease
       Inhibitors/*PHARMACOLOGY  HIV Seropositivity  HIV-1/ENZYMOLOGY/*GENETICS
       Molecular Sequence Data  *Mutation  Polymerase Chain Reaction  Sequence
       Analysis, DNA/METHODS  Sequence Homology, Amino Acid  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, Non-P.H.S.  Support, U.S. Gov't, P.H.S.
       JOURNAL ARTICLE

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

