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 Suzuki, R.
Right arrow Articles by Suzuki, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Suzuki, R.
Right arrow Articles by Suzuki, T.

 Previous Article  |  Next Article 

Journal of Virology, January 2005, p. 1271-1281, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.1271-1281.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Molecular Determinants for Subcellular Localization of Hepatitis C Virus Core Protein

Ryosuke Suzuki,1 Shinichiro Sakamoto,1 Takeya Tsutsumi,1 Akiko Rikimaru,1,2 Keiko Tanaka,3 Takashi Shimoike,1 Kohji Moriishi,4 Takuya Iwasaki,3,5 Kiyohisa Mizumoto,2 Yoshiharu Matsuura,4 Tatsuo Miyamura,1 and Tetsuro Suzuki1*

Department of Virology II, National Institute of Infectious Diseases, Shinjuku-ku,1 Department of Biochemistry, School of Pharmaceutical Sciences, Kitasato University, Minato-ku,2 Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo,3 Research Center for Emerging Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita-shi, Osaka,4 Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki-shi, Nagasaki, Japan5

Received 21 June 2004/ Accepted 26 July 2004

Hepatitis C virus (HCV) core protein is a putative nucleocapsid protein with a number of regulatory functions. In tissue culture cells, HCV core protein is mainly located at the endoplasmic reticulum as well as mitochondria and lipid droplets within the cytoplasm. However, it is also detected in the nucleus in some cells. To elucidate the mechanisms by which cellular trafficking of the protein is controlled, we performed subcellular fractionation experiments and used confocal microscopy to examine the distribution of heterologously expressed fusion proteins involving various deletions and point mutations of the HCV core combined with green fluorescent proteins. We demonstrated that a region spanning amino acids 112 to 152 can mediate association of the core protein not only with the ER but also with the mitochondrial outer membrane. This region contains an 18-amino-acid motif which is predicted to form an amphipathic {alpha}-helix structure. With regard to the nuclear targeting of the core protein, we identified a novel bipartite nuclear localization signal, which requires two out of three basic-residue clusters for efficient nuclear translocation, possibly by occupying binding sites on importin-{alpha}. Differences in the cellular trafficking of HCV core protein, achieved and maintained by multiple targeting functions as mentioned above, may in part regulate the diverse range of biological roles of the core protein.

* Corresponding author. Mailing address: Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, Japan 162-8640. Phone: (81) 3-5285-1111. Fax: (81) 3-5285-1161. E-mail: tesuzuki{at}nih.go.jp.

Journal of Virology, January 2005, p. 1271-1281, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.1271-1281.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ai, L.-S., Lee, Y.-W., Chen, S. S.-L. (2009). Characterization of Hepatitis C Virus Core Protein Multimerization and Membrane Envelopment: Revelation of a Cascade of Core-Membrane Interactions. J. Virol. 83: 9923-9939 [Abstract] [Full Text]  
  • Freundt, E. C., Yu, L., Park, E., Lenardo, M. J., Xu, X.-N. (2009). Molecular Determinants for Subcellular Localization of the Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame 3b Protein. J. Virol. 83: 6631-6640 [Abstract] [Full Text]  
  • Kota, S., Coito, C., Mousseau, G., Lavergne, J.-P., Strosberg, A. D. (2009). Peptide inhibitors of hepatitis C virus core oligomerization and virus production. J. Gen. Virol. 90: 1319-1328 [Abstract] [Full Text]  
  • Roohvand, F., Maillard, P., Lavergne, J.-P., Boulant, S., Walic, M., Andreo, U., Goueslain, L., Helle, F., Mallet, A., McLauchlan, J., Budkowska, A. (2009). Initiation of Hepatitis C Virus Infection Requires the Dynamic Microtubule Network: ROLE OF THE VIRAL NUCLEOCAPSID PROTEIN. J. Biol. Chem. 284: 13778-13791 [Abstract] [Full Text]  
  • Eng, F. J., Walewski, J. L., Klepper, A. L., Fishman, S. L., Desai, S. M., McMullan, L. K., Evans, M. J., Rice, C. M., Branch, A. D. (2009). Internal Initiation Stimulates Production of p8 Minicore, a Member of a Newly Discovered Family of Hepatitis C Virus Core Protein Isoforms. J. Virol. 83: 3104-3114 [Abstract] [Full Text]  
  • Okamoto, K., Mori, Y., Komoda, Y., Okamoto, T., Okochi, M., Takeda, M., Suzuki, T., Moriishi, K., Matsuura, Y. (2008). Intramembrane Processing by Signal Peptide Peptidase Regulates the Membrane Localization of Hepatitis C Virus Core Protein and Viral Propagation. J. Virol. 82: 8349-8361 [Abstract] [Full Text]  
  • Hourioux, C, Patient, R, Morin, A, Blanchard, E, Moreau, A, Trassard, S, Giraudeau, B, Roingeard, P (2007). The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164 increases steatosis in an in vitro cellular model. Gut 56: 1302-1308 [Abstract] [Full Text]  
  • Boulant, S., Targett-Adams, P., McLauchlan, J. (2007). Disrupting the association of hepatitis C virus core protein with lipid droplets correlates with a loss in production of infectious virus. J. Gen. Virol. 88: 2204-2213 [Abstract] [Full Text]  
  • Li, Y., Boehning, D. F., Qian, T., Popov, V. L., Weinman, S. A. (2007). Hepatitis C virus core protein increases mitochondrial ROS production by stimulation of Ca2+ uniporter activity. FASEB J. 21: 2474-2485 [Abstract] [Full Text]  
  • Miyamoto, H., Moriishi, K., Moriya, K., Murata, S., Tanaka, K., Suzuki, T., Miyamura, T., Koike, K., Matsuura, Y. (2007). Involvement of the PA28{gamma}-Dependent Pathway in Insulin Resistance Induced by Hepatitis C Virus Core Protein. J. Virol. 81: 1727-1735 [Abstract] [Full Text]  
  • Shirakura, M., Murakami, K., Ichimura, T., Suzuki, R., Shimoji, T., Fukuda, K., Abe, K., Sato, S., Fukasawa, M., Yamakawa, Y., Nishijima, M., Moriishi, K., Matsuura, Y., Wakita, T., Suzuki, T., Howley, P. M., Miyamura, T., Shoji, I. (2007). E6AP Ubiquitin Ligase Mediates Ubiquitylation and Degradation of Hepatitis C Virus Core Protein. J. Virol. 81: 1174-1185 [Abstract] [Full Text]  
  • Moriishi, K., Mochizuki, R., Moriya, K., Miyamoto, H., Mori, Y., Abe, T., Murata, S., Tanaka, K., Miyamura, T., Suzuki, T., Koike, K., Matsuura, Y. (2007). Critical role of PA28{gamma} in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis. Proc. Natl. Acad. Sci. USA 104: 1661-1666 [Abstract] [Full Text]  
  • Lin, W., Kim, S. S., Yeung, E., Kamegaya, Y., Blackard, J. T., Kim, K. A., Holtzman, M. J., Chung, R. T. (2006). Hepatitis C Virus Core Protein Blocks Interferon Signaling by Interaction with the STAT1 SH2 Domain.. J. Virol. 80: 9226-9235 [Abstract] [Full Text]  
  • Boulant, S., Montserret, R., Hope, R. G., Ratinier, M., Targett-Adams, P., Lavergne, J.-P., Penin, F., McLauchlan, J. (2006). Structural Determinants That Target the Hepatitis C Virus Core Protein to Lipid Droplets. J. Biol. Chem. 281: 22236-22247 [Abstract] [Full Text]  
  • Korenaga, M., Wang, T., Li, Y., Showalter, L. A., Chan, T., Sun, J., Weinman, S. A. (2005). Hepatitis C Virus Core Protein Inhibits Mitochondrial Electron Transport and Increases Reactive Oxygen Species (ROS) Production. J. Biol. Chem. 280: 37481-37488 [Abstract] [Full Text]  
  • Boulant, S., Vanbelle, C., Ebel, C., Penin, F., Lavergne, J.-P. (2005). Hepatitis C Virus Core Protein Is a Dimeric Alpha-Helical Protein Exhibiting Membrane Protein Features. J. Virol. 79: 11353-11365 [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»