This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by You, L.-R.
Right arrow Articles by Lee, Y.-H. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by You, L.-R.
Right arrow Articles by Lee, Y.-H. W.

 Previous Article  |  Next Article 

Journal of Virology, April 1999, p. 2841-2853, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Hepatitis C Virus Core Protein Interacts with Cellular Putative RNA Helicase

Li-Ru You,1 Chun-Ming Chen,1 Tien-Shun Yeh,1 Tzung-Yuan Tsai,1 Ru-Tsun Mai,1 Chi-Hung Lin,2 and Yan-Hwa Wu Lee1,*

Institute of Biochemistry1 and Institute of Microbiology and Immunology,2 National Yang-Ming University, Taipei, Taiwan 112, Republic of China

Received 6 October 1998/Accepted 7 January 1999

The nucleocapsid core protein of hepatitis C virus (HCV) has been shown to trans-act on several viral or cellular promoters. To get insight into the trans-action mechanism of HCV core protein, a yeast two-hybrid cloning system was used for identification of core protein-interacting cellular protein. One such cDNA clone encoding the DEAD box family of putative RNA helicase was obtained. This cellular putative RNA helicase, designated CAP-Rf, exhibits more than 95% amino acid sequence identity to other known RNA helicases including human DBX and DBY, mouse mDEAD3, and PL10, a family of proteins generally involved in translation, splicing, development, or cell growth. In vitro binding or in vivo coimmunoprecipitation studies demonstrated the direct interaction of the full-length/matured form and C-terminally truncated variants of HCV core protein with this targeted protein. Additionally, the protein's interaction domains were delineated at the N-terminal 40-amino-acid segment of the HCV core protein and the C-terminal tail of CAP-Rf, which encompassed its RNA-binding and ATP hydrolysis domains. Immunoblotting or indirect immunofluorescence analysis revealed that the endogenous CAP-Rf was mainly localized in the nucleus and to a lesser extent in the cytoplasm, and when fused with FLAG tag, it colocalized with the HCV core protein either in the cytoplasm or in the nucleus. Similar to other RNA helicases, this cellular RNA helicase has nucleoside triphosphatase-deoxynucleoside triphosphatase activity, but this activity is inhibited by various forms of homopolynucleotides and enhanced by the HCV core protein. Moreover, transient expression of HCV core protein in human hepatoma HuH-7 cells significantly potentiated the trans-activation effect of FLAG-tagged CAP-Rf or untagged CAP-Rf on the luciferase reporter plasmid activity. All together, our results indicate that CAP-Rf is involved in regulation of gene expression and that HCV core protein promotes the trans-activation ability of CAP-Rf, likely via the complex formation and the modulation of the ATPase-dATPase activity of CAP-Rf. These findings provide evidence that HCV may have evolved a distinct mechanism in alteration of host cellular gene expression regulation via the interaction of its nucleocapsid core protein and cellular putative RNA helicase known to participate in all aspects of cellular processes involving RNA metabolism. This feature of core protein may impart pleiotropic effects on host cells, which may partially account for its role in HCV pathogenesis.

* Corresponding author. Mailing address: Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan 112, Republic of China. Phone: 886-2-2826-7124. Fax: 886-2-2826-4843. E-mail: yhwulee{at}ym.edu.tw.

Journal of Virology, April 1999, p. 2841-2853, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Goulet, I., Boisvenue, S., Mokas, S., Mazroui, R., Cote, J. (2008). TDRD3, a novel Tudor domain-containing protein, localizes to cytoplasmic stress granules. Hum Mol Genet 17: 3055-3074 [Abstract] [Full Text]  
  • Huang, W.-H., Mai, R.-T., Wu Lee, Y.-H. (2008). Transcription Factor YY1 and Its Associated Acetyltransferases CBP and p300 Interact with Hepatitis Delta Antigens and Modulate Hepatitis Delta Virus RNA Replication. J. Virol. 82: 7313-7324 [Abstract] [Full Text]  
  • Lee, C.-S., Dias, A. P., Jedrychowski, M., Patel, A. H., Hsu, J. L., Reed, R. (2008). Human DDX3 functions in translation and interacts with the translation initiation factor eIF3. Nucleic Acids Res 36: 4708-4718 [Abstract] [Full Text]  
  • Kang, B.-Y., Tsoi, S., Shan Zhu, , Shenghui Su, , Kay, H. H. (2008). Differential Gene Expression Profiling in HELLP Syndrome Placentas. Reproductive Sciences 15: 285-294 [Abstract]  
  • Beckham, C., Hilliker, A., Cziko, A.-M., Noueiry, A., Ramaswami, M., Parker, R. (2008). The DEAD-Box RNA Helicase Ded1p Affects and Accumulates in Saccharomyces cerevisiae P-Bodies. Mol. Biol. Cell 19: 984-993 [Abstract] [Full Text]  
  • Ariumi, Y., Kuroki, M., Abe, K.-i., Dansako, H., Ikeda, M., Wakita, T., Kato, N. (2007). DDX3 DEAD-Box RNA Helicase Is Required for Hepatitis C Virus RNA Replication. J. Virol. 81: 13922-13926 [Abstract] [Full Text]  
  • Chao, C.-H., Chen, C.-M., Cheng, P.-L., Shih, J.-W., Tsou, A.-P., Wu Lee, Y.-H. (2006). DDX3, a DEAD Box RNA Helicase with Tumor Growth-Suppressive Property and Transcriptional Regulation Activity of the p21waf1/cip1 Promoter, Is a Candidate Tumor Suppressor.. Cancer Res. 66: 6579-6588 [Abstract] [Full Text]  
  • Nashchekin, D., Zhao, J., Visa, N., Daneholt, B. (2006). A Novel Ded1-like RNA Helicase Interacts with the Y-box Protein ctYB-1 in Nuclear mRNP Particles and in Polysomes. J. Biol. Chem. 281: 14263-14272 [Abstract] [Full Text]  
  • Sato, S., Fukasawa, M., Yamakawa, Y., Natsume, T., Suzuki, T., Shoji, I., Aizaki, H., Miyamura, T., Nishijima, M. (2006). Proteomic profiling of lipid droplet proteins in hepatoma cell lines expressing hepatitis C virus core protein.. J Biochem 139: 921-930 [Abstract] [Full Text]  
  • Klein, K. C., Dellos, S. R., Lingappa, J. R. (2005). Identification of Residues in the Hepatitis C Virus Core Protein That Are Critical for Capsid Assembly in a Cell-Free System. J. Virol. 79: 6814-6826 [Abstract] [Full Text]  
  • Schwer, B., Ren, S., Pietschmann, T., Kartenbeck, J., Kaehlcke, K., Bartenschlager, R., Yen, T. S. B., Ott, M. (2004). Targeting of Hepatitis C Virus Core Protein to Mitochondria through a Novel C-Terminal Localization Motif. J. Virol. 78: 7958-7968 [Abstract] [Full Text]  
  • Kikuma, T., Ohtsu, M., Utsugi, T., Koga, S., Okuhara, K., Eki, T., Fujimori, F., Murakami, Y. (2004). Dbp9p, a Member of the DEAD Box Protein Family, Exhibits DNA Helicase Activity. J. Biol. Chem. 279: 20692-20698 [Abstract] [Full Text]  
  • Chong, J.-L., Chuang, R.-Y., Tung, L., Chang, T.-H. (2004). Ded1p, a conserved DExD/H-box translation factor, can promote yeast L-A virus negative-strand RNA synthesis in vitro. Nucleic Acids Res 32: 2031-2038 [Abstract] [Full Text]  
  • Ohkawa, K., Ishida, H., Nakanishi, F., Hosui, A., Ueda, K., Takehara, T., Hori, M., Hayashi, N. (2004). Hepatitis C Virus Core Functions as a Suppressor of Cyclin-dependent Kinase-activating Kinase and Impairs Cell Cycle Progression. J. Biol. Chem. 279: 11719-11726 [Abstract] [Full Text]  
  • Cocude, C., Truong, M.-J., Billaut-Mulot, O., Delsart, V., Darcissac, E., Capron, A., Mouton, Y., Bahr, G. M. (2003). A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication. J. Gen. Virol. 84: 3215-3225 [Abstract] [Full Text]  
  • Moriishi, K., Okabayashi, T., Nakai, K., Moriya, K., Koike, K., Murata, S., Chiba, T., Tanaka, K., Suzuki, R., Suzuki, T., Miyamura, T., Matsuura, Y. (2003). Proteasome Activator PA28{gamma}-Dependent Nuclear Retention and Degradation of Hepatitis C Virus Core Protein. J. Virol. 77: 10237-10249 [Abstract] [Full Text]  
  • Chen, S.-Y., Kao, C.-F., Chen, C.-M., Shih, C.-M., Hsu, M.-J., Chao, C.-H., Wang, S.-H., You, L.-R., Lee, Y.-H. W. (2003). Mechanisms for Inhibition of Hepatitis B Virus Gene Expression and Replication by Hepatitis C Virus Core Protein. J. Biol. Chem. 278: 591-607 [Abstract] [Full Text]  
  • Mahalingam, S., Meanger, J., Foster, P. S., Lidbury, B. A. (2002). The viral manipulation of the host cellular and immune environments to enhance propagation and survival: a focus on RNA viruses. J. Leukoc. Biol. 72: 429-439 [Abstract] [Full Text]  
  • Yague, J., Marina, A., Vazquez, J., Lopez de Castro, J. A. (2001). Major Histocompatibility Complex Class I Molecules Bind Natural Peptide Ligands Lacking the Amino-terminal Binding Residue in Vivo. J. Biol. Chem. 276: 43699-43707 [Abstract] [Full Text]  
  • Moriya, K., Nakagawa, K., Santa, T., Shintani, Y., Fujie, H., Miyoshi, H., Tsutsumi, T., Miyazawa, T., Ishibashi, K., Horie, T., Imai, K., Todoroki, T., Kimura, S., Koike, K. (2001). Oxidative Stress in the Absence of Inflammation in a Mouse Model for Hepatitis C Virus-associated Hepatocarcinogenesis. Cancer Res. 61: 4365-4370 [Abstract] [Full Text]  
  • Wang, T.-H., Rijnbrand, R. C. A., Lemon, S. M. (2000). Core Protein-Coding Sequence, but Not Core Protein, Modulates the Efficiency of Cap-Independent Translation Directed by the Internal Ribosome Entry Site of Hepatitis C Virus. J. Virol. 74: 11347-11358 [Abstract] [Full Text]  
  • Yague, J., Alvarez, I., Rognan, D., Ramos, M., Vazquez, J., de Castro, J. A. L. (2000). An N-Acetylated Natural Ligand of Human Histocompatibility Leukocyte Antigen (Hla)-B39: Classical Major Histocompatibility Complex Class I Proteins Bind Peptides with a Blocked Nh2 Terminus in Vivo. JEM 191: 2083-2092 [Abstract] [Full Text]  
  • Askjaer, P., Rosendahl, R., Kjems, J. (2000). Nuclear Export of the DEAD Box An3 Protein by CRM1 Is Coupled to An3 Helicase Activity. J. Biol. Chem. 275: 11561-11568 [Abstract] [Full Text]  
  • Aoki, H., Hayashi, J., Moriyama, M., Arakawa, Y., Hino, O. (2000). Hepatitis C Virus Core Protein Interacts with 14-3-3 Protein and Activates the Kinase Raf-1. J. Virol. 74: 1736-1741 [Abstract] [Full Text]  
  • Huang, W.-H., Yung, B. Y. M., Syu, W.-J., Lee, Y.-H. W. (2001). The Nucleolar Phosphoprotein B23 Interacts with Hepatitis Delta Antigens and Modulates the Hepatitis Delta Virus RNA Replication. J. Biol. Chem. 276: 25166-25175 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»