Hepatoma cell density promotes claudin-1 and scavenger receptor BI expression and hepatitis C virus internalization

Schwarz, A.K., Grove, J. , Hu, K., Mee, C.J., Balfe, P. and McKeating, J.A. (2009) Hepatoma cell density promotes claudin-1 and scavenger receptor BI expression and hepatitis C virus internalization. Journal of Virology, 83(23), pp. 12407-12414. (doi: 10.1128/JVI.01552-09) (PMID:19776133) (PMCID:PMC2786758)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Grove, Dr Joe
Authors: Schwarz, A.K., Grove, J., Hu, K., Mee, C.J., Balfe, P., and McKeating, J.A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1098-5514

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