       Document 1098
 DOCN  M9591098
 TI    Impaired infectivity of HIV-1 after a single point mutation in the POL
       gene to escape the effect of a protease inhibitor in vitro.
 DT    9509
 AU    Kuroda MJ; el-Farrash MA; Choudhury S; Harada S; Department of
       Biodefence and Medical Virology, Kumamoto; University School of
       Medicine, Japan.
 SO    Virology. 1995 Jun 20;210(1):212-6. Unique Identifier : AIDSLINE
       MED/95313357
 AB    To examine whether the mutation of protease in an HIV-1 resistant to a
       protease inhibitor affects the virus phenotype in vitro, the infectivity
       of the protease inhibitor-escape-virus was compared to that of the
       parent virus. In different T-cell lines, the infectivity of the escape
       virus was impaired by 10-fold compared to the parent virus. MT-4 cell
       killing by the escape virus, measured using the MTT assay, was much
       weaker than that by the parent virus. The escape virus contained more
       unprocessed Pr55gag than the parent virus. A delayed appearance of
       mature p24 in cells chronically infected with the escape virus was also
       noticed by the pulse-chase method. The same findings were obtained using
       pNL432 (HIV-1 DNA molecular clone) with the same mutation in the
       protease gene. Despite the lack of a significant difference in virus
       binding, less unintegrated and integrated DNA was detected in MT-4 cells
       infected with the escape virus compared to the parent virus. The
       impaired infectivity of the escape virus may be explained by the
       inefficient maturation of Gag proteins, due to the mutated protease,
       which may affect an early step in the virus life cycle.
 DE    Antigens, CD/ANALYSIS/PHYSIOLOGY  Antigens, CD4/ANALYSIS/PHYSIOLOGY
       Cell Line  Comparative Study  DNA, Viral/ANALYSIS/BIOSYNTHESIS  *Genes,
       pol  Human  HIV Core Protein p24/ANALYSIS/BIOSYNTHESIS  HIV Protease
       Inhibitors/*PHARMACOLOGY  HIV-1/DRUG EFFECTS/*PHYSIOLOGY/*PATHOGENICITY
       Kinetics  *Point Mutation  Support, Non-U.S. Gov't  Time Factors  *Virus
       Replication  JOURNAL ARTICLE

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

