Inhibition of the Interferon- Inducible Protein Kinase PKR by HCV E2 Protein-Reference-Cited by-同舟云学术

Inhibition of the Interferon- Inducible Protein Kinase PKR by HCV E2 Protein

Published:1999-07-02 Issue:5424 Volume:285 Page:107-110
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Taylor Deborah R.¹,Shi Stephanie T.¹,Romano Patrick R.²,Barber Glen N.³,Lai Michael M. C.¹⁴

Affiliation:

1. Department of Molecular Microbiology and Immunology and

2. Small Molecule Therapeutics, Monmouth Junction, NJ 08852, USA.

3. University of Miami, School of Medicine, Miami, FL 33136, USA.

4. Howard Hughes Medical Institute, University of Southern California, School of Medicine, Los Angeles, CA 90089, USA.

Abstract

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 eIF2α, 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference28 articles.

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5. M. J. Clemens in (2) pp. 575–605. Four autophosphorylation sites (serine 83 and threonines 88 89 and 90) have been identified in the RNA-binding domain of PKR (D. R. Taylor and M. B. Mathews in preparation). These sequences are not conserved between human and rodent species. These sites and 10 others have been observed by mass spectroscopy by X. Zhang et al. [ Anal. Chem. 70 2050 (1998)].

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