Farquhar, M. J., Hu, K., Harris, H. J., Davis, C. , Brimacombe, C. L., Fletcher, S. J., Baumert, T. F., Rappoport, J. Z., Balfe, P. and McKeating, J. A. (2012) Hepatitis C virus induces CD81 and claudin-1 endocytosis. Journal of Virology, 86(8), pp. 4305-4316. (doi: 10.1128/JVI.06996-11) (PMID:22318146) (PMCID:PMC3318669)
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Abstract
Hepatitis C virus (HCV) leads to progressive liver disease and hepatocellular carcinoma. Current treatments are only partially effective, and new therapies targeting viral and host pathways are required. Virus entry into a host cell provides a conserved target for therapeutic intervention. Tetraspanin CD81, scavenger receptor class B member I, and the tight-junction proteins claudin-1 and occludin have been identified as essential entry receptors. Limited information is available on the role of receptor trafficking in HCV entry. We demonstrate here that anti-CD81 antibodies inhibit HCV infection at late times after virus internalization, suggesting a role for intracellular CD81 in HCV infection. Several tetraspanins have been reported to internalize via motifs in their C-terminal cytoplasmic domains; however, CD81 lacks such motifs, leading several laboratories to suggest a limited role for CD81 endocytosis in HCV entry. We demonstrate CD81 internalization via a clathrin- and dynamin-dependent process, independent of its cytoplasmic domain, suggesting a role for associated partner proteins in regulating CD81 trafficking. Live cell imaging demonstrates CD81 and claudin-1 coendocytosis and fusion with Rab5 expressing endosomes, supporting a role for this receptor complex in HCV internalization. Receptor-specific antibodies and HCV particles increase CD81 and claudin-1 endocytosis, supporting a model wherein HCV stimulates receptor trafficking to promote particle internalization.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Davis, Dr Chris |
| Authors: | Farquhar, M. J., Hu, K., Harris, H. J., Davis, C., Brimacombe, C. L., Fletcher, S. J., Baumert, T. F., Rappoport, J. Z., Balfe, P., and McKeating, J. A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Journal of Virology |
| Publisher: | American Society for Microbiology |
| ISSN: | 0022-538X |
| ISSN (Online): | 1098-5514 |
| Published Online: | 15 April 2012 |
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