Lipoprotein Receptors and Lipid Enzymes in Hepatitis C Virus Entry and Early Steps of Infection

Figure 2

Architecture of human hepatocytes and proposed model for HCV LVPs. Interaction at the surface of the hepatocyte with their entry factors involved in lipid metabolism. For reasons of clarity, only lipoprotein receptors of HCV are indicated; also HCV is the only lipid particle depicted, transiting in the blood, where it would flow with lipoproteins. Two primary human hepatocytes are depicted (cells nos. 1 and 2), organized laterally around the apical membrane (bile pole). De, desmosome; TJ, tight junction; Mi, microvilli; Mito, mitochondria; RER, rough endoplasmic reticulum. Two nuclei per cell are represented, since hepatocytes are often bi-nucleated. HCV (depicted as an LVP) extravasates from blood to encounter the hepatocyte basolateral membrane. At this stage, it interacts with: (i) SR-BI in an apoE-dependent manner; this could be facilitated by HDL binding to their own attachement domain on SR-BI (through apoAI), and is most likely apoCI-dependent; (ii) LDL-R in an apoB-dependent manner. Normal lipoproteins are also depicted as HDL, LDL and VLDL. Corresponding marker apolipoproteins are indicated (apoAI, green; apoB, blue; apoCI, magenta; apoE, orange). NPC1L1 is present at the apical membrane of hepatocytes (red). Since the exact way HCV interacts with this receptor is currently unclear, no virion has been depicted in its vicinity. Photographic credit for TEM images: Perrault M and Pécheur EI, unpublished data.