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

来源：

SCIENCE | 1999年 / 285卷 / 5424期

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

页码：107 / 110

页数：4

共 23 条

[11] Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase (vol 397, pg 271, 1999)
Harding, HP
Zhang, YH
Ron, D
[J]. NATURE, 1999, 398 (6722) : 90 - 90
[12] Hepatitis C virus core protein interacts with heterogeneous nuclear ribonucleoprotein K
Hsieh, TY
Matsumoto, M
Chou, HC
Schneider, R
Hwang, SB
Lee, AS
Lai, MMC
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (28) : 17651 - 17659
[13] JIMENEZGARCIA LF, 1993, J CELL SCI, V106, P11
[14] FUNCTIONAL EXPRESSION AND RNA-BINDING ANALYSIS OF THE INTERFERON-INDUCED, DOUBLE-STRANDED RNA-ACTIVATED, 68,000-MR PROTEIN-KINASE IN A CELL-FREE SYSTEM
KATZE, MG
WAMBACH, M
WONG, ML
GARFINKEL, M
MEURS, E
CHONG, K
WILLIAMS, BRG
HOVANESSIAN, AG
BARBER, GN
[J]. MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (11) : 5497 - 5505
[15] MONOCLONAL-ANTIBODIES TO AN INTERFERON-INDUCED MR 68,000 PROTEIN AND THEIR USE FOR THE DETECTION OF DOUBLE-STRANDED RNA-DEPENDENT PROTEIN-KINASE IN HUMAN-CELLS
LAURENT, AG
KRUST, B
GALABRU, J
SVAB, J
HOVANESSIAN, AG
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (13) : 4341 - 4345
[16] ADENOVIRUS VIRUS-ASSOCIATED RNA AND TRANSLATION CONTROL
MATHEWS, MB
SHENK, T
[J]. JOURNAL OF VIROLOGY, 1991, 65 (11) : 5657 - 5662
[17] MATHEWS MB, 1996, TRANSLATIONAL CONTRO, P505
[18] Inhibition of the double-stranded RNA-dependent protein kinase PKR by mammalian ribosomes
Raine, DA
Jeffrey, IW
Clemens, MJ
[J]. FEBS LETTERS, 1998, 436 (03) : 343 - 348
[19] STRUCTURAL REQUIREMENTS FOR DOUBLE-STRANDED-RNA BINDING, DIMERIZATION, AND ACTIVATION OF THE HUMAN EIF-2-ALPHA KINASE DAI IN SACCHAROMYCES-CEREVISIAE
ROMANO, PR
GREEN, SR
BARBER, GN
MATHEWS, MB
HINNEBUSCH, AG
[J]. MOLECULAR AND CELLULAR BIOLOGY, 1995, 15 (01) : 365 - 378
[20] Taylor DR, 1996, MOL CELL BIOL, V16, P6295

← 1 2 3 →