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
Google Scholar
Right arrow Articles by Schwarz, A. K.
Right arrow Articles by McKeating, J. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schwarz, A. K.
Right arrow Articles by McKeating, J. A.

 Previous Article  |  Next Article 

Journal of Virology, December 2009, p. 12407-12414, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01552-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Hepatoma Cell Density Promotes Claudin-1 and Scavenger Receptor BI Expression and Hepatitis C Virus Internalization{triangledown}

Anne K. Schwarz, Joe Grove, Ke Hu, Christopher J. Mee, Peter Balfe,* and Jane A. McKeating

Hepatitis C Research Group, Institute For Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom

Received 27 July 2009/ Accepted 15 September 2009

Hepatitis C virus (HCV) entry occurs via a pH- and clathrin-dependent endocytic pathway and requires a number of cellular factors, including CD81, the tight-junction proteins claudin 1 (CLDN1) and occludin, and scavenger receptor class B member I (SR-BI). HCV tropism is restricted to the liver, where hepatocytes are tightly packed. Here, we demonstrate that SR-BI and CLDN1 expression is modulated in confluent human hepatoma cells, with both receptors being enriched at cell-cell junctions. Cellular contact increased HCV pseudoparticle (HCVpp) and HCV particle (HCVcc) infection and accelerated the internalization of cell-bound HCVcc, suggesting that the cell contact modulation of receptor levels may facilitate the assembly of receptor complexes required for virus internalization. CLDN1 overexpression in subconfluent cells was unable to recapitulate this effect, whereas increased SR-BI expression enhanced HCVpp entry and HCVcc internalization, demonstrating a rate-limiting role for SR-BI in HCV internalization.


* Corresponding author. Mailing address: Hepatitis C Research Group, Institute for Biomedical Research, University of Birmingham, 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 23 September 2009.


Journal of Virology, December 2009, p. 12407-12414, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01552-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.