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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Mee, C. J.
Right arrow Articles by McKeating, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mee, C. J.
Right arrow Articles by McKeating, J. A.

 Previous Article  |  Next Article 

Journal of Virology, January 2008, p. 461-470, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01894-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Effect of Cell Polarization on Hepatitis C Virus Entry{triangledown}

Christopher J. Mee, Joe Grove, Helen J. Harris, Ke Hu, Peter Balfe,* and Jane A. McKeating

Division of Immunity and Infection, Institute for Biomedical Research, University of Birmingham, Birmingham, United Kingdom

Received 30 August 2007/ Accepted 12 October 2007

The primary reservoir for hepatitis C virus (HCV) replication in vivo is believed to be hepatocytes within the liver. Three host cell molecules have been reported to be important entry factors for receptors for HCV: the tetraspanin CD81, scavenger receptor BI (SR-BI), and the tight-junction (TJ) protein claudin 1 (CLDN1). The recent discovery of a TJ protein as a critical coreceptor highlighted the importance of studying the effect(s) of TJ formation and cell polarization on HCV entry. The colorectal adenocarcinoma Caco-2 cell line forms polarized monolayers containing functional TJs and was found to express the CD81, SR-BI, and CLDN1 proteins. Viral receptor expression levels increased upon polarization, and CLDN1 relocalized from the apical pole of the lateral cell membrane to the lateral cell-cell junction and basolateral domains. In contrast, expression and localization of the TJ proteins ZO-1 and occludin 1 were unchanged upon polarization. HCV infected polarized and nonpolarized Caco-2 cells to comparable levels, and entry was neutralized by anti-E2 monoclonal antibodies, demonstrating glycoprotein-dependent entry. HCV pseudoparticle infection and recombinant HCV E1E2 glycoprotein interaction with polarized Caco-2 cells occurred predominantly at the apical surface. Disruption of TJs significantly increased HCV entry. These data support a model where TJs provide a physical barrier for viral access to receptors expressed on lateral and basolateral cellular domains.

* Corresponding author. Mailing address: Division of Immunity and Infection, Institute for Biomedical Research, University of Birmingham, Vincent Drive, Birmingham B15 2TT, United Kingdom. Phone: (44) 121 414 8174. Fax: (44) 121 414 3599. E-mail: p.balfe{at}bham.ac.uk

{triangledown} Published ahead of print on 24 October 2007.

Journal of Virology, January 2008, p. 461-470, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01894-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Benedicto, I., Molina-Jimenez, F., Bartosch, B., Cosset, F.-L., Lavillette, D., Prieto, J., Moreno-Otero, R., Valenzuela-Fernandez, A., Aldabe, R., Lopez-Cabrera, M., Majano, P. L. (2009). The Tight Junction-Associated Protein Occludin Is Required for a Postbinding Step in Hepatitis C Virus Entry and Infection. J. Virol. 83: 8012-8020 [Abstract] [Full Text]  
  • Mee, C. J., Harris, H. J., Farquhar, M. J., Wilson, G., Reynolds, G., Davis, C., van IJzendoorn, S. C. D., Balfe, P., McKeating, J. A. (2009). Polarization Restricts Hepatitis C Virus Entry into HepG2 Hepatoma Cells. J. Virol. 83: 6211-6221 [Abstract] [Full Text]  
  • Liu, S., Yang, W., Shen, L., Turner, J. R., Coyne, C. B., Wang, T. (2009). Tight Junction Proteins Claudin-1 and Occludin Control Hepatitis C Virus Entry and Are Downregulated during Infection To Prevent Superinfection. J. Virol. 83: 2011-2014 [Abstract] [Full Text]  
  • Grove, J., Nielsen, S., Zhong, J., Bassendine, M. F., Drummer, H. E., Balfe, P., McKeating, J. A. (2008). Identification of a Residue in Hepatitis C Virus E2 Glycoprotein That Determines Scavenger Receptor BI and CD81 Receptor Dependency and Sensitivity to Neutralizing Antibodies. J. Virol. 82: 12020-12029 [Abstract] [Full Text]  
  • Timpe, J M, McKeating, J A (2008). Hepatitis C virus entry: possible targets for therapy. Gut 57: 1728-1737 [Full Text]  
  • Snooks, M. J., Bhat, P., Mackenzie, J., Counihan, N. A., Vaughan, N., Anderson, D. A. (2008). Vectorial Entry and Release of Hepatitis A Virus in Polarized Human Hepatocytes. J. Virol. 82: 8733-8742 [Abstract] [Full Text]  
  • Farquhar, M. J., Harris, H. J., Diskar, M., Jones, S., Mee, C. J., Nielsen, S. U., Brimacombe, C. L., Molina, S., Toms, G. L., Maurel, P., Howl, J., Herberg, F. W., van IJzendoorn, S. C. D., Balfe, P., McKeating, J. A. (2008). Protein Kinase A-Dependent Step(s) in Hepatitis C Virus Entry and Infectivity. J. Virol. 82: 8797-8811 [Abstract] [Full Text]  
  • Harris, H. J., Farquhar, M. J., Mee, C. J., Davis, C., Reynolds, G. M., Jennings, A., Hu, K., Yuan, F., Deng, H., Hubscher, S. G., Han, J. H., Balfe, P., McKeating, J. A. (2008). CD81 and Claudin 1 Coreceptor Association: Role in Hepatitis C Virus Entry. J. Virol. 82: 5007-5020 [Abstract] [Full Text]  
  • Yang, W., Qiu, C., Biswas, N., Jin, J., Watkins, S. C., Montelaro, R. C., Coyne, C. B., Wang, T. (2008). Correlation of the Tight Junction-like Distribution of Claudin-1 to the Cellular Tropism of Hepatitis C Virus. J. Biol. Chem. 283: 8643-8653 [Abstract] [Full Text]  
  • von Hahn, T., Rice, C. M. (2008). Hepatitis C Virus Entry. J. Biol. Chem. 283: 3689-3693 [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»