title: Role of low-density lipoprotein receptor in the hepatitis C virus life cycle.
abstract: Hepatitis C virus (HCV) particles are known to be in complex with lipoproteins. As a result of this interaction, the low-density lipoprotein (LDL) receptor (LDLR) has been proposed as a potential entry factor for HCV; however, its implication in virus entry remains unclear. Here, we reinvestigated the role of the LDLR in the HCV life cycle by comparing virus entry to the mechanism of lipoprotein uptake. A small interfering RNA targeting the LDLR in Huh-7 cells reduced HCV infectivity, confirming that this receptor plays a role in the life cycle of HCV generated in cell culture. However, kinetics of internalization were much faster for lipoproteins than for infectious HCV particles. Furthermore, a decrease in HCV RNA replication was observed by blocking the LDLR with a specific antibody, and this was associated with an increase in the ratio of phosphatidylethanolamine to phosphatidylcholine in host cells. Nevertheless, a soluble form of the LDLR inhibited both HCV entry into the hepatocytes and its binding to the LDLR expressed on Chinese hamster ovary cells, suggesting a direct interaction between the HCV particle and the LDLR. Finally, we showed that modification of HCV particles by lipoprotein lipase (LPL) reduces HCV infectivity and increases HCV binding to LDLR. Importantly, LPL treatment also induced an increase in RNA internalization, suggesting that LDLR, at least in some conditions, leads to nonproductive internalization of HCV.
  
  
  CONCLUSIONS
  The LDLR is not essential for infectious HCV particle entry, whereas the physiological function of this receptor is important for optimal replication of the HCV genome.
authors: Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors: Anna
authors: A
authors: Albecka
authors: Sandrine
authors: S
authors: Belouzard
authors: Anne
authors: A
authors: Op de Beeck
authors: Véronique
authors: V
authors: Descamps
authors: Lucie
authors: L
authors: Goueslain
authors: Justine
authors: J
authors: Bertrand-Michel
authors: François
authors: F
authors: Tercé
authors: Gilles
authors: G
authors: Duverlie
authors: Yves
authors: Y
authors: Rouillé
authors: Jean
authors: J
authors: Dubuisson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D057809:HEK293 Cells; D016174:Hepacivirus / Q000254:growth & development* / Q000472:pathogenicity / Q000502:physiology*; D022781:Hepatocytes / Q000473:pathology / Q000821:virology; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000821:virology; D008018:Life Cycle Stages / Q000502:physiology*; D010053:Ovary / Q000166:cytology / Q000821:virology; D012367:RNA, Viral / Q000378:metabolism; D011973:Receptors, LDL / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D000906:Antibodies; D012367:RNA, Viral; D011973:Receptors, LDL