New Insights in Recurrent HCV Infection after Liver Transplantation

Hsu, Shih-Hsien; Yeh, Ming-Lun; Wang, Shen-Nien

Physiologically, SR-BI binds a variety of lipoproteins (e.g., HDL and LDL) and is involved in bidirectional cholesterol transport at the cell membrane. The LEL of SR-BI has been demonstrated to interact with E2 HVR1 [93] . Recent studies suggest that the interplay between lipoproteins, SR-BI, and HCV envelope glycoproteins is required for HCV entry [94, 95] . CLDNs are critical components of tight junctions, which regulate paracellular permeability and polarity. CLDN1, a 23 kDa four-transmembrane protein, is predominantly expressed in the liver [96] . Intriguingly, CLDN1 may localize to the tight junction and the basolateral surfaces of hepatocytes [97] . Recent studies suggest that nonjunctional CLDN1 may be also involved in HCV entry [48, 98] . OCLN is a 65 kDa four transmembrane protein expressed in the tight junction of polarized cells. Several studies have shown that OCLN is probably involved in the late postbinding event of HCV entry [99, 100] . As HCV circulates in the blood in association with LDL and VLDL, the LDL receptor has also been proposed as an attachment and/or entry factor for HCV [100] . The LDLR has been shown to mediate the internalization of serum-derived HCV into CD81-deficient HepG2 cells by binding virus-LDL particles [101] . Since cholesterol has been shown to be necessary for HCV cell entry, it is rational that other cholesterol-uptake receptors might also have a role in this process. More recently, Niemann-Pick C1-like 1 cholesterol absorption receptor (NPC1L1), a 13-transmembranedomain cell surface cholesterol-sensing receptor, has been demonstrated as a new HCV entry factor [102] .