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
  • [1] The PKR protein kinase - An interferon-inducible regulator of cell growth and differentiation
    Samuel, CE
    Kuhen, KL
    George, CX
    Ortega, LG
    RendeFournier, R
    Tanaka, H
    [J]. INTERNATIONAL JOURNAL OF HEMATOLOGY, 1997, 65 (03) : 227 - 237
  • [2] A diminished activation capacity of the interferon-inducible protein kinase PKR in human T lymphocytes
    Li, SY
    Nagai, K
    Koromilas, AE
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 2000, 267 (06): : 1598 - 1606
  • [3] Dominant negative function by an alternatively spliced form of the interferon-inducible protein kinase PKR
    Li, SY
    Koromilas, AE
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (17) : 13881 - 13890
  • [4] Activation of the interferon-inducible protein kinase PKR by Hepatocellular carcinoma derived-Hepatitis C virus core protein
    Delhem, N
    Sabile, A
    Gajardo, R
    Podevin, P
    Abadie, A
    Blaton, MA
    Kremsdorf, D
    Beretta, L
    Brechot, C
    [J]. ONCOGENE, 2001, 20 (41) : 5836 - 5845
  • [5] Activation of the interferon-inducible protein kinase PKR by Hepatocellular carcinoma derived-Hepatitis C virus core protein
    Nadvia Delhem
    Abdelmajid Sabile
    Rodrigo Gajardo
    Philippe Podevin
    Annie Abadie
    Maria Agnes Blaton
    Dina Kremsdorf
    Laura Beretta
    Christian Brechot
    [J]. Oncogene, 2001, 20 : 5836 - 5845
  • [6] Interferon-inducible ubiquitin E2, Ubc8, is a conjugating enzyme for protein ISGylation
    Kim, KI
    Giannakopoulos, NV
    Virgin, HW
    Zhang, DE
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (21) : 9592 - 9600
  • [7] Ebola virus protein VP35 inhibits activation of the interferon-inducible kinase PKR by RNA
    Eitan, Maayan
    Osman, Farhat
    Namer, Lise Sarah
    Eliahu, Einav
    Banai, Yona
    Kaempfer, Raymond
    [J]. CYTOKINE, 2008, 43 (03) : 298 - 298
  • [8] Characterization of the heparin-mediated activation of PKR, the interferon-inducible RNA-dependent protein kinase
    George, CX
    Thomis, DC
    McCormack, SJ
    Svahn, CM
    Samuel, CE
    [J]. VIROLOGY, 1996, 221 (01) : 180 - 188
  • [9] THE INTERFERON-INDUCIBLE PROTEIN-KINASE PKR MODULATES THE TRANSCRIPTIONAL ACTIVATION OF IMMUNOGLOBULIN-KAPPA GENE
    KOROMILAS, AE
    CANTIN, C
    CRAIG, AWB
    JAGUS, R
    HISCOTT, J
    SONENBERG, N
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (43) : 25426 - 25434
  • [10] Human interferon-γ mRNA autoregulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR
    Ben-Asouli, Y
    Banai, Y
    Pel-Or, Y
    Shir, A
    Kaempfer, R
    [J]. CELL, 2002, 108 (02) : 221 - 232