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

被引:572
|
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 50 条
  • [21] SEQUENCE OF THE MURINE INTERFERON-INDUCIBLE RNA-DEPENDENT PROTEIN-KINASE (PKR) DEDUCED FROM GENOMIC CLONES
    TANAKA, H
    SAMUEL, CE
    [J]. GENE, 1995, 153 (02) : 283 - 284
  • [22] Inhibition of interferon-inducible MxA protein expression by hepatitis B virus capsid protein
    Rosmorduc, O
    Sirma, H
    Soussan, P
    Gordien, E
    Lebon, P
    Horisberger, M
    Bréchot, C
    Kremsdorf, D
    [J]. JOURNAL OF GENERAL VIROLOGY, 1999, 80 : 1253 - 1262
  • [23] Structural organization of the human gene (PKR) encoding an interferon-inducible RNA-Dependent protein kinase (PKR) and differences from its mouse homolog
    Kuhen, KL
    Shen, XY
    Carlisle, ER
    Richardson, AL
    Weier, HUG
    Tanaka, H
    Samuel, CE
    [J]. GENOMICS, 1996, 36 (01) : 197 - 201
  • [25] Inhibition of hepatitis B virus replication by the interferon-inducible MxA protein
    Gordien, E
    Rosmorduc, O
    Peltekian, C
    Garreau, F
    Bréchot, C
    Kremsdorf, D
    [J]. JOURNAL OF VIROLOGY, 2001, 75 (06) : 2684 - 2691
  • [26] THE LA ANTIGEN INHIBITS THE ACTIVATION OF THE INTERFERON-INDUCIBLE PROTEIN-KINASE PKR BY SEQUESTERING AND UNWINDING DOUBLE-STRANDED-RNA
    XIAO, QR
    SHARP, TV
    JEFFREY, IW
    JAMES, MC
    PRUIJN, GJM
    VANVENROOIJ, WJ
    CLEMENS, MJ
    [J]. NUCLEIC ACIDS RESEARCH, 1994, 22 (13) : 2512 - 2518
  • [27] The fragile X syndrome repeats form RNA hairpins that do not activate the interferon-inducible protein kinase, PKR, but are cut by Dicer
    Handa, V
    Saha, T
    Usdin, K
    [J]. NUCLEIC ACIDS RESEARCH, 2003, 31 (21) : 6243 - 6248
  • [28] Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways
    Wong, AHT
    Tam, NWN
    Yang, YL
    Cuddihy, AR
    Li, SY
    Kirchhoff, S
    Hauser, H
    Decker, T
    Koromilas, AE
    [J]. EMBO JOURNAL, 1997, 16 (06): : 1291 - 1304
  • [29] REGULATION OF THE INTERFERON-INDUCIBLE EIF-2-ALPHA PROTEIN-KINASE BY SMALL RNAS
    CLEMENS, MJ
    LAING, KG
    JEFFREY, IW
    SCHOFIELD, A
    SHARP, TV
    ELIA, A
    MATYS, V
    JAMES, MC
    TILLERAY, VJ
    [J]. BIOCHIMIE, 1994, 76 (08) : 770 - 778
  • [30] Induction of CD4 expression and human immunodeficiency virus type 1 replication by mutants of the interferon-inducible protein kinase PKR
    Nagai, K
    Wong, AHT
    Li, SY
    Tam, NWN
    Cuddihy, AR
    Sonenberg, N
    Mathews, MB
    Hiscott, J
    Wainberg, MA
    Koromilas, AE
    [J]. JOURNAL OF VIROLOGY, 1997, 71 (02) : 1718 - 1725