Project Details
Abstract
Hepatitis C virus (HCV) is a major cause of chronic non-A, non-B hepatitis. Patients with
chronic HCV infection are at increased risk of developing liver cirrhosis and hepatocellular
carcinoma. To study the molecular mechanism of HCV infection and replication, a selectable,
subgenomic HCV replication system, named replicon, has been developed. Recently, by
replacing the coding areas of non-structural proteins with those from a particular clone
derived from fulminant hepatitis C, complete HCV infection and replication cycles can be
achieved in cell culture. Although much progress has been achieved, the present systems
cannot support HCV infection and replication with HCV-positive serum samples as an
infection source, hindering their usefulness in clinical applications. By use of a molecular
screening strategy, a hepatic factor, Sip-L, was found capable of supporting HCV replication
in an otherwise non-permissive cell line (Yeh et al., J. Virol. 2001). The Sip-L expressing
cells could be infected by half of the HCV-positive serum samples tested (preliminary data).
Sip-L is a member of the Cupin superfamily. Homologs of Sip-L were found among
evolutionally distance species, indicating a yet unidentified important function. An isoform
of Sip-L, named eSip-L or MTCBP-1, has recently been found to be a binding protein of the
membrane-type 1 matrix metalloprotenase (MT1-MMP, a membranous protein), suggesting
a possible role of Sip-L in cell entry of HCV. Our laboratory has recently discovered that the
Sip-L expressing cells could be used to propagate HCV indefinitely, albeit in a low
replication level (preliminary data). It is therefore possible that Sip-L is a
cofactor/co-receptor for HCV infection. To investigate the molecular mechanism whereby
Sip-L assists HCV infection and to further modify this system to achieve a higher HCV
replication level, we wish to identify the cellular factors involved in Sip-L assisted HCV
replication.
Project IDs
Project ID:PA9506-0072
External Project ID:NSC95-3112-B182-008
External Project ID:NSC95-3112-B182-008
Status | Finished |
---|---|
Effective start/end date | 01/05/06 → 30/04/07 |
Keywords
- Hepatitis C virus
- replication
- hepatocellular carcinoma
- Sip-L
- cellular factor
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.