Document 0785
 DOCN  M9650785
 TI    Identification of a clinical isolate of HIV-1 with an isoleucine at
       position 82 of the protease which retains susceptibility to protease
       inhibitors.
 DT    9605
 AU    King RW; Winslow DL; Garber S; Scarnati HT; Bachelor L; Stack S; Otto
       MJ; DuPont Merck Pharmaceutical Company, Glenolden, PA 19036, USA.
 SO    Antiviral Res. 1995 Sep;28(1):13-24. Unique Identifier : AIDSLINE
       MED/96105494
 AB    The HIV-1 protease (PR) is essential for the production of mature
       virions. As such, it has become a target for the development of anti-HIV
       chemotherapeutics. Multiple passages of virus in cell culture in the
       presence of PR inhibitors have resulted in the selection of variants
       with decreased sensitivity to inhibitors of the PR. The most common
       alteration observed is a single amino acid change at position 82. This
       particular position has been well characterized by several laboratories
       as being important for the susceptibility of the virus to inhibitors of
       PR function. Mutations which result in the substitution of the wild-type
       valine with alanine, phenylalanine, threonine or isoleucine at position
       82 of the PR have been associated with decreased sensitivity to several
       PR inhibitors. We describe here a clinical strain of HIV-1 that contains
       an isoleucine at position 82 of the PR instead of the usual valine. This
       strain is unique in that it was isolated from a patient that was
       anti-retroviral naive, and in the past, variants at position 82 of the
       PR have only been found after treatment of patients or cell culture with
       PR inhibitors. Moreover, this virus remains sensitive to PR inhibitors
       of the cyclic urea and C-2 symmetrical diol classes.
 DE    Amino Acid Sequence  Base Sequence  Binding Sites  Cell Line  DNA, Viral
       Genes, Viral  Human  HIV Protease/*CHEMISTRY/DRUG EFFECTS/GENETICS  HIV
       Protease Inhibitors/*PHARMACOLOGY  HIV-1/DRUG EFFECTS/*ENZYMOLOGY/GROWTH
       & DEVELOPMENT/ISOLATION &  PURIF  *Isoleucine  Male  Molecular Sequence
       Data  Recombination, Genetic  Sequence Homology, Nucleic Acid
       Structure-Activity Relationship  Thailand  Tumor Cells, Cultured
       JOURNAL ARTICLE

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