Identification of Cellular Factors Capable of Enhancing Sip-L Assisted Hcv Replication (I)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

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
StatusFinished
Effective start/end date01/05/0630/04/07

Keywords

  • Hepatitis C virus
  • replication
  • hepatocellular carcinoma
  • Sip-L
  • cellular factor

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