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Hepatitis C virus (HCV) is a major cause of post-transfusion and community-acquired hepatitis in the world. 1 HCV is a plus-stranded RNA virus that infects approximately 2-4% of the world population and causes a variety of liver diseases; including chronic hepatitis, cirrhosis, liver failure and hepatocellular carcinoma. 2 Interferon α (IFNα) with or without ribavirin is the only clinically licensed agent for treatment of patients with HCV infection. IFNs are well-characterised components of the innate host defence against viral infections. Many studies have shown that the Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT) signalling pathway plays an important role in the biological activity of IFNs. The requirement for STAT1 and STAT2 in IFN signalling and action has been well documented through gene knockout studies. 3 4
The selective association of a virus with a target cell is usually determined by an interaction between the viral glycoproteins (E1 and E2) and specific cell surface receptor(s). It is likely that a two-step process defines the event leading to virus entry into a cell. As the first step for HCV to recognise a cell, it may bind to the mannose-binding lectins DC-SIGN and L-SIGN. These cell surface proteins are believed to function as HCV capture receptors. 5 The second step of viral entry is not as clear, and several candidate receptors for HCV have recently been proposed. For example, the CD81 tetraspanin, 6 scavenger receptor class B type I (SR-BI), 7 low-density lipoprotein (LDL) receptor 8 and asialoglycoprotein receptor 9 may serve as potential candidate receptors for HCV. Among these molecules there is mounting evidence that CD81 and SR-BI are necessary for HCV entry. 10 Whereas the role of CD81 in HCV entry is now well documented, 10 11 the contribution of SR-BI in this process remains unclear.
SR-BI is a 509 amino acid glycoprotein with two cytoplasmic C-terminal and N-terminal domains separated by a large extracellular domain. The mouse SR-BI mediates selective uptake of high-density lipoprotein (HDL) cholesterol ester (CE) into transfected Chinese hamster ovary (CHO) cells. 12 Our previous report shows that the human homologue of SR-BI, CD36 and LIMPII Analogous-1 (hSR-BI/CLA-1), like the mouse homologue, functions as a receptor for HDL. 13 - 19 hSR-BI/CLA-1 is like the mouse homologue because...