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J Virol. 2009 Jun;83(11):5477-84. doi: 10.1128/JVI.02262-08. Epub 2009 Mar 18.

Residues in a highly conserved claudin-1 motif are required for hepatitis C virus entry and mediate the formation of cell-cell contacts.

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  • 1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Abstract

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 W(30)-GLW(51)-C(54)-C(64). 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.

PMID:
19297469
[PubMed - indexed for MEDLINE]
PMCID:
PMC2681980
Free PMC Article
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