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Molecular and Cellular Biology, September 1998, p. 5208-5218, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Control of PKR Protein Kinase by Hepatitis C Virus Nonstructural 5A Protein: Molecular Mechanisms of Kinase Regulation

Michael Gale Jr.,1 Collin M. Blakely,2 Bart Kwieciszewski,2 Seng-Lai Tan,1 Michelle Dossett,1 Norina M. Tang,1 Marcus J. Korth,2 Stephen J. Polyak,3 David R. Gretch,3 and Michael G. Katze1,2,*

Department of Microbiology, School of Medicine,1 and Regional Primate Research Center,2 University of Washington, Seattle, Washington 98195, and Department of Laboratory Medicine, University of Washington and Pacific Medical Center, Seattle, Washington 981443

Received 13 February 1998/Returned for modification 13 April 1998/Accepted 16 June 1998

The PKR protein kinase is a critical component of the cellular antiviral and antiproliferative responses induced by interferons. Recent evidence indicates that the nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) can repress PKR function in vivo, possibly allowing HCV to escape the antiviral effects of interferon. NS5A presents a unique tool by which to study the molecular mechanisms of PKR regulation in that mutations within a region of NS5A, termed the interferon sensitivity-determining region (ISDR), are associated with sensitivity of HCV to the antiviral effects of interferon. In this study, we investigated the mechanisms of NS5A-mediated PKR regulation and the effect of ISDR mutations on this regulatory process. We observed that the NS5A ISDR, though necessary, was not sufficient for PKR interactions; we found that an additional 26 amino acids (aa) carboxyl to the ISDR were required for NS5A-PKR complex formation. Conversely, we localized NS5A binding to within PKR aa 244 to 296, recently recognized as a PKR dimerization domain. Consistent with this observation, we found that NS5A from interferon-resistant HCV genotype 1b disrupted kinase dimerization in vivo. NS5A-mediated disruption of PKR dimerization resulted in repression of PKR function and inhibition of PKR-mediated eIF-2alpha phosphorylation. Introduction of multiple ISDR mutations abrogated the ability of NS5A to bind to PKR in mammalian cells and to inhibit PKR in a yeast functional assay. These results indicate that mutations within the PKR-binding region of NS5A, including those within the ISDR, can disrupt the NS5A-PKR interaction, possibly rendering HCV sensitive to the antiviral effects of interferon. We propose a model of PKR regulation by NS5A which may have implications for therapeutic strategies against HCV.

* Corresponding author. Mailing address: Department of Microbiology, School of Medicine, University of Washington, Box 357242, Seattle, WA 98195. Phone: (206) 543-8837. Fax: (206) 685-0305. E-mail: honey{at}u.washington.edu.

Molecular and Cellular Biology, September 1998, p. 5208-5218, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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  • Su, A. I., Pezacki, J. P., Wodicka, L., Brideau, A. D., Supekova, L., Thimme, R., Wieland, S., Bukh, J., Purcell, R. H., Schultz, P. G., Chisari, F. V. (2002). Genomic analysis of the host response to hepatitis C virus infection. Proc. Natl. Acad. Sci. USA 99: 15669-15674 [Abstract] [Full Text]  
  • Bukh, J., Pietschmann, T., Lohmann, V., Krieger, N., Faulk, K., Engle, R. E., Govindarajan, S., Shapiro, M., St. Claire, M., Bartenschlager, R. (2002). Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees. Proc. Natl. Acad. Sci. USA 99: 14416-14421 [Abstract] [Full Text]  
  • Rivas-Estilla, A. M., Svitkin, Y., Lopez Lastra, M., Hatzoglou, M., Sherker, A., Koromilas, A. E. (2002). PKR-Dependent Mechanisms of Gene Expression from a Subgenomic Hepatitis C Virus Clone. J. Virol. 76: 10637-10653 [Abstract] [Full Text]  
  • Sarrazin, C., Herrmann, E., Bruch, K., Zeuzem, S. (2002). Hepatitis C Virus Nonstructural 5A Protein and Interferon Resistance: a New Model for Testing the Reliability of Mutational Analyses. J. Virol. 76: 11079-11090 [Abstract] [Full Text]  
  • Takahashi, A., Iwasaki, Y., Miyaike, J., Taniguchi, H., Shimomura, H., Hanafusa, T., Yumoto, Y., Moriya, A., Koide, N., Tsuji, T. (2002). Quantitative Analysis of p40/p46 and p69/p71 Forms of 2',5'-Oligoadenylate Synthetase mRNA by Competitive PCR and Its Clinical Application. Clin. Chem. 48: 1551-1559 [Abstract] [Full Text]  
  • He, Y., Nakao, H., Tan, S.-L., Polyak, S. J., Neddermann, P., Vijaysri, S., Jacobs, B. L., Katze, M. G. (2002). Subversion of Cell Signaling Pathways by Hepatitis C Virus Nonstructural 5A Protein via Interaction with Grb2 and P85 Phosphatidylinositol 3-Kinase. J. Virol. 76: 9207-9217 [Abstract] [Full Text]  
  • Pietschmann, T., Lohmann, V., Kaul, A., Krieger, N., Rinck, G., Rutter, G., Strand, D., Bartenschlager, R. (2002). Persistent and Transient Replication of Full-Length Hepatitis C Virus Genomes in Cell Culture. J. Virol. 76: 4008-4021 [Abstract] [Full Text]  
  • Friebe, P., Lohmann, V., Krieger, N., Bartenschlager, R. (2001). Sequences in the 5' Nontranslated Region of Hepatitis C Virus Required for RNA Replication. J. Virol. 75: 12047-12057 [Abstract] [Full Text]  
  • Gil, J., Rullas, J., Alcami, J., Esteban, M. (2001). MC159L protein from the poxvirus molluscum contagiosum virus inhibits NF-{kappa}B activation and apoptosis induced by PKR. J. Gen. Virol. 82: 3027-3034 [Abstract] [Full Text]  
  • Lusida, M. I., Nagano-Fujii, M., Nidom, C. A., Soetjipto, , Handajani, R., Fujita, T., Oka, K., Hotta, H. (2001). Correlation between Mutations in the Interferon Sensitivity-Determining Region of NS5A Protein and Viral Load of Hepatitis C Virus Subtypes 1b, 1c, and 2a. J. Clin. Microbiol. 39: 3858-3864 [Abstract] [Full Text]  
  • Samuel, C. E. (2001). Antiviral Actions of Interferons. Clin. Microbiol. Rev. 14: 778-809 [Abstract] [Full Text]  
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  • Chung, R. T., He, W., Saquib, A., Contreras, A. M., Xavier, R. J., Chawla, A., Wang, T. C., Schmidt, E. V. (2001). Hepatitis C virus replication is directly inhibited by IFN-alpha in a full-length binary expression system. Proc. Natl. Acad. Sci. USA 10.1073/pnas.171319698v1 [Abstract] [Full Text]  
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  • Pietschmann, T., Lohmann, V., Rutter, G., Kurpanek, K., Bartenschlager, R. (2001). Characterization of Cell Lines Carrying Self-Replicating Hepatitis C Virus RNAs. J. Virol. 75: 1252-1264 [Abstract] [Full Text]  
  • Lohmann, V., Körner, F., Dobierzewska, A., Bartenschlager, R. (2001). Mutations in Hepatitis C Virus RNAs Conferring Cell Culture Adaptation. J. Virol. 75: 1437-1449 [Abstract] [Full Text]  
  • Bergqvist, A., Rice, C. M. (2001). Transcriptional Activation of the Interleukin-2 Promoter by Hepatitis C Virus Core Protein. J. Virol. 75: 772-781 [Abstract] [Full Text]  
  • Nousbaum, J.-B., Polyak, S. J., Ray, S. C., Sullivan, D. G., Larson, A. M., Carithers, R. L. Jr., Gretch, D. R. (2000). Prospective Characterization of Full-Length Hepatitis C Virus NS5A Quasispecies during Induction and Combination Antiviral Therapy. J. Virol. 74: 9028-9038 [Abstract] [Full Text]  
  • Schlender, J., Bossert, B., Buchholz, U., Conzelmann, K.-K. (2000). Bovine Respiratory Syncytial Virus Nonstructural Proteins NS1 and NS2 Cooperatively Antagonize Alpha/Beta Interferon-Induced Antiviral Response. J. Virol. 74: 8234-8242 [Abstract] [Full Text]  
  • Naganuma, A., Nozaki, A., Tanaka, T., Sugiyama, K., Takagi, H., Mori, M., Shimotohno, K., Kato, N. (2000). Activation of the Interferon-Inducible 2'-5'-Oligoadenylate Synthetase Gene by Hepatitis C Virus Core Protein. J. Virol. 74: 8744-8750 [Abstract] [Full Text]  
  • Bartenschlager, R., Lohmann, V. (2000). Replication of hepatitis C virus. J. Gen. Virol. 81: 1631-1648 [Full Text]  
  • François, C., Duverlie, G., Rebouillat, D., Khorsi, H., Castelain, S., Blum, H. E., Gatignol, A., Wychowski, C., Moradpour, D., Meurs, E. F. (2000). Expression of Hepatitis C Virus Proteins Interferes with the Antiviral Action of Interferon Independently of PKR-Mediated Control of Protein Synthesis. J. Virol. 74: 5587-5596 [Abstract] [Full Text]  
  • Gale, M. Jr., Tan, S.-L., Katze, M. G. (2000). Translational Control of Viral Gene Expression in Eukaryotes. Microbiol. Mol. Biol. Rev. 64: 239-280 [Abstract] [Full Text]  
  • Chung, K. M., Lee, J., Kim, J.-E., Song, O.-K., Cho, S., Lim, J., Seedorf, M., Hahm, B., Jang, S. K. (2000). Nonstructural Protein 5A of Hepatitis C Virus Inhibits the Function of Karyopherin beta 3. J. Virol. 74: 5233-5241 [Abstract] [Full Text]  
  • Leyssen, P., De Clercq, E., Neyts, J. (2000). Perspectives for the Treatment of Infections with Flaviviridae. Clin. Microbiol. Rev. 13: 67-82 [Abstract] [Full Text]  
  • Neddermann, P., Clementi, A., De Francesco, R. (1999). Hyperphosphorylation of the Hepatitis C Virus NS5A Protein Requires an Active NS3 Protease, NS4A, NS4B, and NS5A Encoded on the Same Polyprotein. J. Virol. 73: 9984-9991 [Abstract] [Full Text]  
  • Heim, M. H., Moradpour, D., Blum, H. E. (1999). Expression of Hepatitis C Virus Proteins Inhibits Signal Transduction through the Jak-STAT Pathway. J. Virol. 73: 8469-8475 [Abstract] [Full Text]  
  • Oliver Koch, J., Bartenschlager, R. (1999). Modulation of Hepatitis C Virus NS5A Hyperphosphorylation by Nonstructural Proteins NS3, NS4A, and NS4B. J. Virol. 73: 7138-7146 [Abstract] [Full Text]  
  • Chung, R. Y., Saeki, Y., Chiocca, E. A. (1999). B-myb Promoter Retargeting of Herpes Simplex Virus gamma 34.5 Gene-Mediated Virulence toward Tumor and Cycling Cells. J. Virol. 73: 7556-7564 [Abstract] [Full Text]  
  • Pawlotsky, J.-M., Germanidis, G., Frainais, P.-O., Bouvier, M., Soulier, A., Pellerin, M., Dhumeaux, D. (1999). Evolution of the Hepatitis C Virus Second Envelope Protein Hypervariable Region in Chronically Infected Patients Receiving Alpha Interferon Therapy. J. Virol. 73: 6490-6499 [Abstract] [Full Text]  
  • Gale, M. Jr., Kwieciszewski, B., Dossett, M., Nakao, H., Katze, M. G. (1999). Antiapoptotic and Oncogenic Potentials of Hepatitis C Virus Are Linked to Interferon Resistance by Viral Repression of the PKR Protein Kinase. J. Virol. 73: 6506-6516 [Abstract] [Full Text]  
  • Patel, R. C., Vestal, D. J., Xu, Z., Bandyopadhyay, S., Guo, W., Erme, S. M., Williams, B. R. G., Sen, G. C. (1999). DRBP76, a Double-stranded RNA-binding Nuclear Protein, Is Phosphorylated by the Interferon-induced Protein Kinase, PKR. J. Biol. Chem. 274: 20432-20437 [Abstract] [Full Text]  
  • Taylor, D. R., Shi, S. T., Romano, P. R., Barber, G. N., Lai, M. M. (1999). Inhibition of the Interferon- Inducible Protein Kinase PKR by HCV E2 Protein. Science 285: 107-110 [Abstract] [Full Text]  
  • Tan, S.-L., Nakao, H., He, Y., Vijaysri, S., Neddermann, P., Jacobs, B. L., Mayer, B. J., Katze, M. G. (1999). NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-dependent manner and perturbs mitogenic signaling. Proc. Natl. Acad. Sci. USA 96: 5533-5538 [Abstract] [Full Text]  
  • Ghosh, A., Steele, R, Meyer, K, Ray, R, Ray, R. (1999). Hepatitis C virus NS5A protein modulates cell cycle regulatory genes and promotes cell growth. J. Gen. Virol. 80: 1179-1183 [Abstract]  
  • Song, J, Fujii, M, Wang, F, Itoh, M, Hotta, H (1999). The NS5A protein of hepatitis C virus partially inhibits the antiviral activity of interferon. J. Gen. Virol. 80: 879-886 [Abstract]  
  • Ueda, Y., Chaudhuri, G. (2000). Differential Expression of B1-containing Transcripts in Leishmania-exposed Macrophages. J. Biol. Chem. 275: 19428-19432 [Abstract] [Full Text]  
  • Daher, A., Longuet, M., Dorin, D., Bois, F., Segeral, E., Bannwarth, S., Battisti, P.-L., Purcell, D. F., Benarous, R., Vaquero, C., Meurs, E. F., Gatignol, A. (2001). Two Dimerization Domains in the Trans-activation Response RNA-binding Protein (TRBP) Individually Reverse the Protein Kinase R Inhibition of HIV-1 Long Terminal Repeat Expression. J. Biol. Chem. 276: 33899-33905 [Abstract] [Full Text]  
  • Gong, G., Waris, G., Tanveer, R., Siddiqui, A. (2001). Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proc. Natl. Acad. Sci. USA 98: 9599-9604 [Abstract] [Full Text]  


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