Lipoprotein receptors in hepatitis C virus entry — a structural view

Hepatitis C virus (HCV) exploits the physiological pathways of lipid uptake and transport via utilization of several lipoprotein receptors, including the low-density lipoprotein receptor (LDLR), very low-density lipoprotein receptor (VLDLR), and scavenger receptor class B type I (SR-BI). Together with essential entry receptors such as CD81, claudin-1, and occludin, these factors form a dynamic and interdependent network that enables efficient attachment and entry but also shapes viral tropism. Recent structural insights, particularly the high-resolution structures of LDLR and its complex with apoB-100, provide a molecular framework for understanding how apolipoproteins associated with lipoviral particles could engage lipoprotein receptors and may mimic native lipoprotein uptake. Major questions remain elusive - particularly regarding the precise role of SR-BI and how its activity contributes to HCV entry, as well as the exact sequence, kinetics, and interdependence of receptor interactions. This review aims to provide an overview of lipoprotein receptors involved in HCV entry, with a particular focus on structural and mechanistic insights.