Send to

Choose Destination
See comment in PubMed Commons below
Sci Rep. 2013 Nov 22;3:3243. doi: 10.1038/srep03243.

HCV NS3 protease enhances liver fibrosis via binding to and activating TGF-β type I receptor.

Author information

1] Micro-signaling Regulation Technology Unit, RIKEN Center for Life Science Technologies, Saitama 351-0198, Japan [2] Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Kanagawa 223-8522, Japan [3] Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., Hiroshima 739-1195, Japan.


Viruses sometimes mimic host proteins and hijack the host cell machinery. Hepatitis C virus (HCV) causes liver fibrosis, a process largely mediated by the overexpression of transforming growth factor (TGF)-β and collagen, although the precise underlying mechanism is unknown. Here, we report that HCV non-structural protein 3 (NS3) protease affects the antigenicity and bioactivity of TGF-β2 in (CAGA)9-Luc CCL64 cells and in human hepatic cell lines via binding to TGF-β type I receptor (TβRI). Tumor necrosis factor (TNF)-α facilitates this mechanism by increasing the colocalization of TβRI with NS3 protease on the surface of HCV-infected cells. An anti-NS3 antibody against computationally predicted binding sites for TβRI blocked the TGF-β mimetic activities of NS3 in vitro and attenuated liver fibrosis in HCV-infected chimeric mice. These data suggest that HCV NS3 protease mimics TGF-β2 and functions, at least in part, via directly binding to and activating TβRI, thereby enhancing liver fibrosis.

[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center