LDL receptor

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The LDL receptor (LDLR) transports cholesterol-containing lipoproteins into the cell by endocytosis via clathrin-coated pits. Receptor-ligand complexes are delivered into endosomes where low pH induces the release of lipoproteins which then proceed to lysosomes where free cholesterol is generated by cholesterol ester hydrolysis (65). The apolipoprotein B (apoB)-containing LDL and apolipoprotein E (apoE)-containing very low-density lipoproteins (VLDL) are the major LDLR ligands. As HCV is able to associate with LDL and VLDL in serum (66, 67), the LDLR was suggested to be a putative HCV receptor candidate. The LDLR has been shown to mediate internalize serum-derived HCV by binding virus-LDL particles (31). Anti-LDLR antibodies as well as anti-apoB and apoE antibodies were able to inhibit HCV endocytosis (17, 31, 40, 68). It could also be demonstrated that LDLR plays a role in an early step of serum-derived HCV infection of primary human hepatocytes (64). However, studies using the HCVpp system where HCV is not associated with lipoproteins suggest that LDLR does not appear to play a role for infection of Huh7 cells with HCVpp (17). Further studies using HCVcc and human hepatocytes will allow gaining more insight into the role of LDLR in HCV infection.

Despite the numerous experimental data demonstrating the importance of the above described receptors in HCV infection, none of these molecules has a liver-specific expression profile as it would be expected for receptors of a hepatotropic virus. Moreover, all HCV permissive cell lines identified so far express CD81, SR-BI and CLDN1 and are of hepatic origin but various cell lines of non-hepatic origin expressing these receptors are non permissive for HCV (17, 22, 27, 47), suggesting that additional liver specific factor(s) which are still to be discovered are required for HCV infection.