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 Nakai, K.
Right arrow Articles by Matsuura, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakai, K.
Right arrow Articles by Matsuura, Y.

 Previous Article  |  Next Article 

Journal of Virology, November 2006, p. 11265-11273, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01203-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Oligomerization of Hepatitis C Virus Core Protein Is Crucial for Interaction with the Cytoplasmic Domain of E1 Envelope Protein{triangledown}

Kousuke Nakai,1 Toru Okamoto,1 Tomomi Kimura-Someya,2 Koji Ishii,2 Chang Kweng Lim,1 Hideki Tani,1 Eiko Matsuo,1 Takayuki Abe,1 Yoshio Mori,1 Tetsuro Suzuki,2 Tatsuo Miyamura,2 Jack H. Nunberg,3 Kohji Moriishi,1 and Yoshiharu Matsuura1*

Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka,1 Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan,2 Montana Biotechnology Center, The University of Montana, Missoula, Montana 598123

Received 9 June 2006/ Accepted 28 August 2006

Hepatitis C virus (HCV) contains two membrane-associated envelope glycoproteins, E1 and E2, which assemble as a heterodimer in the endoplasmic reticulum (ER). In this study, predictive algorithms and genetic analyses of deletion mutants and glycosylation site variants of the E1 glycoprotein were used to suggest that the glycoprotein can adopt two topologies in the ER membrane: the conventional type I membrane topology and a polytopic topology in which the protein spans the ER membrane twice with an intervening cytoplasmic loop (amino acid residues 288 to 360). We also demonstrate that the E1 glycoprotein is able to associate with the HCV core protein, but only upon oligomerization of the core protein in the presence of tRNA to form capsid-like structures. Yeast two-hybrid and immunoprecipitation analyses reveal that oligomerization of the core protein is promoted by amino acid residues 72 to 91 in the core. Furthermore, the association between the E1 glycoprotein and the assembled core can be recapitulated using a fusion protein containing the putative cytoplasmic loop of the E1 glycoprotein. This fusion protein is also able to compete with the intact E1 glycoprotein for binding to the core. Mutagenesis of the cytoplasmic loop of E1 was used to define a region of four amino acids (residues 312 to 315) that is important for interaction with the assembled HCV core. Taken together, our studies suggest that interaction between the self-oligomerized HCV core and the E1 glycoprotein is mediated through the cytoplasmic loop present in a polytopic form of the E1 glycoprotein.

* Corresponding author. Mailing address: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-8340. Fax: 81-6-6879-8269. E-mail: matsuura{at}biken.osaka-u.ac.jp.

{triangledown} Published ahead of print on 13 September 2006.

Journal of Virology, November 2006, p. 11265-11273, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01203-06
Copyright © 2006, 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]  
  • Phan, T., Beran, R. K. F., Peters, C., Lorenz, I. C., Lindenbach, B. D. (2009). Hepatitis C Virus NS2 Protein Contributes to Virus Particle Assembly via Opposing Epistatic Interactions with the E1-E2 Glycoprotein and NS3-NS4A Enzyme Complexes. J. Virol. 83: 8379-8395 [Abstract] [Full Text]  
  • Suzuki, R., Winkelmann, E. R., Mason, P. W. (2009). Construction and Characterization of a Single-Cycle Chimeric Flavivirus Vaccine Candidate That Protects Mice against Lethal Challenge with Dengue Virus Type 2. J. Virol. 83: 1870-1880 [Abstract] [Full Text]  
  • Zhang, C., Liu, Y., Liu, L., Lou, Z., Zhang, H., Miao, H., Hu, X., Pang, Y., Qiu, B. (2008). Rice black streaked dwarf virus P9-1, an {alpha}-helical protein, self-interacts and forms viroplasms in vivo. J. Gen. Virol. 89: 1770-1776 [Abstract] [Full Text]  
  • Aizaki, H., Morikawa, K., Fukasawa, M., Hara, H., Inoue, Y., Tani, H., Saito, K., Nishijima, M., Hanada, K., Matsuura, Y., Lai, M. M. C., Miyamura, T., Wakita, T., Suzuki, T. (2008). Critical Role of Virion-Associated Cholesterol and Sphingolipid in Hepatitis C Virus Infection. J. Virol. 82: 5715-5724 [Abstract] [Full Text]  
  • Murray, C. L., Jones, C. T., Tassello, J., Rice, C. M. (2007). Alanine Scanning of the Hepatitis C Virus Core Protein Reveals Numerous Residues Essential for Production of Infectious Virus. J. Virol. 81: 10220-10231 [Abstract] [Full Text]  
  • Jones, C. T., Murray, C. L., Eastman, D. K., Tassello, J., Rice, C. M. (2007). Hepatitis C Virus p7 and NS2 Proteins Are Essential for Production of Infectious Virus. J. Virol. 81: 8374-8383 [Abstract] [Full Text]  
  • Agnihothram, S. S., York, J., Trahey, M., Nunberg, J. H. (2007). Bitopic Membrane Topology of the Stable Signal Peptide in the Tripartite Junin Virus GP-C Envelope Glycoprotein Complex. J. Virol. 81: 4331-4337 [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»