Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein

被引:571
作者
Taylor, DR
Shi, ST
Romano, PR
Barber, GN
Lai, MMC [1 ]
机构
[1] Univ So Calif, Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90089 USA
[2] Univ So Calif, Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90089 USA
[3] Small Mol Therapeut, Monmouth Junction, NJ 08852 USA
[4] Univ Miami, Sch Med, Miami, FL 33136 USA
关键词
D O I
10.1126/science.285.5424.107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Most isolates of hepatitis C virus (HCV) infections are resistant to interferon, the only available therapy, but the mechanism underlying this resistance has not been defined. Here it is shown that the HCV envelope protein E2 contains a sequence identical with phosphorylation sites of the interferon-inducible protein kinase PKR and the translation initiation factor eIF2 alpha, a target of PKR. E2 inhibited the kinase activity of PKR and blocked its inhibitory effect on protein synthesis and cell growth. This interaction of E2 and PKR may be one mechanism by which HCV circumvents the antiviral effect of interferon.
引用
收藏
页码:107 / 110
页数:4
相关论文
共 23 条
  • [1] Ultrastructural localization of interferon-inducible double-stranded RNA-activated enzymes in human cells
    Besse, S
    Rebouillat, D
    Marie, I
    Francine-Puvion-Dutilleul
    Hovanessian, AG
    [J]. EXPERIMENTAL CELL RESEARCH, 1998, 239 (02) : 379 - 392
  • [2] GENETIC ORGANIZATION AND DIVERSITY OF THE HEPATITIS-C VIRUS
    CHOO, QL
    RICHMAN, KH
    HAN, JH
    BERGER, K
    LEE, C
    DONG, C
    GALLEGOS, C
    COIT, D
    MEDINASELBY, A
    BARR, PJ
    WEINER, AJ
    BRADLEY, DW
    KUO, G
    HOUGHTON, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (06) : 2451 - 2455
  • [3] CLEMENS MJ, 1996, TRANSLATIONAL CONTRO, P575
  • [4] A retention signal necessary and sufficient for endoplasmic reticulum localization maps to the transmembrane domain of hepatitis C virus glycoprotein E2
    Cocquerel, L
    Meunier, JC
    Pillez, A
    Wychowski, C
    Dubuisson, J
    [J]. JOURNAL OF VIROLOGY, 1998, 72 (03) : 2183 - 2191
  • [5] MAMMALIAN EUKARYOTIC INITIATION FACTOR-2-ALPHA KINASES FUNCTIONALLY SUBSTITUTE FOR GCN2 PROTEIN-KINASE IN THE GCN4 TRANSLATIONAL CONTROL MECHANISM OF YEAST
    DEVER, TE
    CHEN, JJ
    BARBER, GN
    CIGAN, AM
    FENG, L
    DONAHUE, TF
    LONDON, IM
    KATZE, MG
    HINNEBUSCH, AG
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (10) : 4616 - 4620
  • [6] Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection
    Enomoto, N
    Sakuma, I
    Asahina, Y
    Kurosaki, M
    Murakami, T
    Yamamoto, C
    Ogura, Y
    Izumi, N
    Marumo, F
    Sato, C
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (02) : 77 - 81
  • [7] Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: Molecular mechanisms of kinase regulation
    Gale, M
    Blakely, CM
    Kwieciszewski, B
    Tan, SL
    Dossett, M
    Tang, NM
    Korth, MJ
    Polyak, SJ
    Gretch, DR
    Katze, MG
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (09) : 5208 - 5218
  • [8] Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein
    Gale, MJ
    Korth, MJ
    Tang, NM
    Tan, SL
    Hopkins, DA
    Dever, TE
    Polyak, SJ
    Gretch, DR
    Katze, MG
    [J]. VIROLOGY, 1997, 230 (02) : 217 - 227
  • [9] 2 RNA-BINDING MOTIFS IN THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN-KINASE, DAI
    GREEN, SR
    MATHEWS, MB
    [J]. GENES & DEVELOPMENT, 1992, 6 (12B) : 2478 - 2490
  • [10] Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
    Harding, HP
    Zhang, YH
    Ron, D
    [J]. NATURE, 1999, 397 (6716) : 271 - 274