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Journal of Virology, June 2009, p. 5477-5484, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02262-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Residues in a Highly Conserved Claudin-1 Motif Are Required for Hepatitis C Virus Entry and Mediate the Formation of Cell-Cell Contacts{triangledown}

Lisa Cukierman, Laurent Meertens, Claire Bertaux, Francis Kajumo, and Tatjana Dragic*

Albert Einstein College of Medicine, Department of Microbiology and Immunology, 1300 Morris Park Avenue, Bronx, New York 10461

Received 28 October 2008/ Accepted 13 March 2009

Claudin-1, a component of tight junctions between liver hepatocytes, is a hepatitis C virus (HCV) late-stage entry cofactor. To investigate the structural and functional roles of various claudin-1 domains in HCV entry, we applied a mutagenesis strategy. Putative functional intracellular claudin-1 domains were not important. However, we identified seven novel residues in the first extracellular loop that are critical for entry of HCV isolates drawn from six different subtypes. Most of the critical residues belong to the highly conserved claudin motif W30-GLW51-C54-C64. Alanine substitutions of these residues did not impair claudin-1 cell surface expression or lateral protein interactions within the plasma membrane, including claudin-1-claudin-1 and claudin-1-CD81 interactions. However, these mutants no longer localized to cell-cell contacts. Based on our observations, we propose that cell-cell contacts formed by claudin-1 may generate specialized membrane domains that are amenable to HCV entry.

* Corresponding author. Mailing address: Albert Einstein College of Medicine, Department of Microbiology and Immunology, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-3282. Fax: (718) 430-8711. E-mail: tdragic{at}aecom.yu.edu

{triangledown} Published ahead of print on 18 March 2009.

Journal of Virology, June 2009, p. 5477-5484, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02262-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Schwarz, A. K., Grove, J., Hu, K., Mee, C. J., Balfe, P., McKeating, J. A. (2009). Hepatoma Cell Density Promotes Claudin-1 and Scavenger Receptor BI Expression and Hepatitis C Virus Internalization. J. Virol. 83: 12407-12414 [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]  


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