COPII cargo claudin-12 promotes hepatitis C virus entry.

Hepatitis C virus (HCV) is one of major cause of liver diseases worldwide. Claudin-1 (CLDN1), CLDN6 and CLDN9 have been identified as COPII cargoes and co-receptors for HCV. However, whether CLDN12 is a COPII cargo and whether CLDN12 promotes HCV entry remain to be elucidated. Although CLDN12 does not contain a critical valine residue the carboxy terminus, CLDN 12 was found to associate with Sec24C, a key cargo sorting component of COPII transport machinery. Perturbation of Sec24C reduced the surface level of CLDN12. Silencing CLDN12 reduces HCV entry, while overexpression of CLDN12 promotes HCV entry. Moreover, CLDN12 was revealed to interact with CD81, a major HCV receptor. Collectively, we propose that CLDN12 is important for HCV entry and is a cargo of COPII transport. This article is protected by copyright. All rights reserved.