EFFECT OF 2 NOVEL INHIBITORS OF THE HUMAN-IMMUNODEFICIENCY-VIRUS PROTEASE ON THE MATURATION OF THE HIV GAG AND GAG-POL POLYPROTEINS

被引：21

作者：

OVERTON, HA ^{[1
]}

MCMILLAN, DJ ^{[1
]}

GRIDLEY, SJ ^{[1
]}

BRENNER, J ^{[1
]}

REDSHAW, S ^{[1
]}

MILLS, JS ^{[1
]}

机构：

[1] ROCHE PROD LTD,DEPT CHEM,WELWYN GARDEN CIT AL7 3AY,HERTS,ENGLAND

来源：

VIROLOGY | 1990年 / 179卷 / 01期

关键词：

D O I：

10.1016/0042-6822(90)90326-M

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The ability of two novel synthetic compounds to inhibit the HIV protease-mediated processing of HIV-1 precursor polyproteins was investigated in an in vitro gag-protease mixed lysate assay system and in an assay using recombinant baculoviruses engineered to express the HIV-1 gag and pol genes in cultured insect cells. With the in vitro mixed lysate assay we have shown that both compounds at 1 μM can completely inhibit the HIV-1 and HIV-2 protease-mediated release of p24 from the HIV-1 gag precursor at pH 5.5 and pH 7.0. In the intracellular baculovirus system these compounds were shown to inhibit the protease-mediated maturation of gag and also the excision of the protease moiety from its precursor. © 1990.

引用

页码：508 / 511

页数：4

共 11 条

[1] HUMAN IMMUNODEFICIENCY VIRUS PROTEASE EXPRESSED IN ESCHERICHIA-COLI EXHIBITS AUTOPROCESSING AND SPECIFIC MATURATION OF THE GAG PRECURSOR [J].

DEBOUCK, C ;

GORNIAK, JG ;

STRICKLER, JE ;

MEEK, TD ;

METCALF, BW ;

ROSENBERG, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (24) :8903-8906

[2] RAPID COLORIMETRIC ASSAY FOR CELL-GROWTH AND SURVIVAL - MODIFICATIONS TO THE TETRAZOLIUM DYE PROCEDURE GIVING IMPROVED SENSITIVITY AND RELIABILITY [J].

DENIZOT, F ;

LANG, R .

JOURNAL OF IMMUNOLOGICAL METHODS, 1986, 89 (02) :271-277

[3] AN 11-KDA FORM OF HUMAN IMMUNODEFICIENCY VIRUS PROTEASE EXPRESSED IN ESCHERICHIA-COLI IS SUFFICIENT FOR ENZYMATIC-ACTIVITY [J].

GRAVES, MC ;

LIM, JJ ;

HEIMER, EP ;

KRAMER, RA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (08) :2449-2453

[4] CHARACTERIZATION OF RIBOSOMAL FRAMESHIFTING IN HIV-1 GAG-POL EXPRESSION [J].

JACKS, T ;

POWER, MD ;

MASIARZ, FR ;

LUCIW, PA ;

BARR, PJ ;

VARMUS, HE .

NATURE, 1988, 331 (6153) :280-283

[5] ACTIVE HUMAN IMMUNODEFICIENCY VIRUS PROTEASE IS REQUIRED FOR VIRAL INFECTIVITY [J].

KOHL, NE ;

EMINI, EA ;

SCHLEIF, WA ;

DAVIS, LJ ;

HEIMBACH, JC ;

DIXON, RAF ;

SCOLNICK, EM ;

SIGAL, IS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (13) :4686-4690

[6] ACTIVE-SITE MUTAGENESIS OF THE AIDS VIRUS PROTEASE AND ITS ALLEVIATION BY TRANS COMPLEMENTATION [J].

LEGRICE, SFJ ;

MILLS, J ;

MOUS, J .

EMBO JOURNAL, 1988, 7 (08) :2547-2553

[7] A SINGLE 66-KILODALTON POLYPEPTIDE PROCESSED FROM THE HUMAN IMMUNODEFICIENCY VIRUS TYPE-2 POL POLYPROTEIN IN ESCHERICHIA-COLI DISPLAYS REVERSE-TRANSCRIPTASE ACTIVITY [J].

LEGRICE, SFJ ;

ZEHNLE, R ;

MOUS, J .

JOURNAL OF VIROLOGY, 1988, 62 (07) :2525-2529

[8]

LEGRICE SFJ, 1989, J BIOL CHEM, V264, P14092

[9] PROCESSING PROTEASE AND REVERSE-TRANSCRIPTASE FROM HUMAN IMMUNODEFICIENCY VIRUS TYPE-I POLYPROTEIN IN ESCHERICHIA-COLI [J].

MOUS, J ;

HEIMER, EP ;

LEGRICE, SFJ .

JOURNAL OF VIROLOGY, 1988, 62 (04) :1433-1436

[10] THE PROTEASE AND GAG GENE-PRODUCTS OF THE HUMAN IMMUNODEFICIENCY VIRUS - AUTHENTIC CLEAVAGE AND POST-TRANSLATIONAL MODIFICATION IN AN INSECT CELL EXPRESSION SYSTEM [J].

OVERTON, HA ;

FUJII, Y ;

PRICE, IR ;

JONES, IM .

VIROLOGY, 1989, 170 (01) :107-116

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