title: The tight junction proteins claudin-1, -6, and -9 are entry cofactors for hepatitis C virus.
abstract: Hepatitis C virus (HCV) is a major cause of liver disease in humans. The CD81 tetraspanin is necessary but not sufficient for HCV penetration into hepatocytes, and it was recently reported that the tight junction protein claudin-1 is a critical HCV entry cofactor. Here, we confirm the role of claudin-1 in HCV entry. In addition, we show that claudin-6 and claudin-9 expressed in CD81(+) cells also enable the entry of HCV pseudoparticles derived from six of the major genotypes. Whereas claudin-1, -6, and -9 function equally well as entry cofactors in endothelial cells, claudin-1 is more efficient in hepatoma cells. This suggests that additional cellular factors modulate the ability of claudins to function as HCV entry cofactors. Our work has generated novel and essential means to investigate the mechanism of HCV penetration into hepatocytes and the role of the claudin protein family in HCV dissemination, replication, and pathogenesis.
authors.affiliation: Albert Einstein College of Medicine, Department of Microbiology and Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Meertens
authors.forename: Claire
authors.initials: C
authors.lastname: Bertaux
authors.forename: Lisa
authors.initials: L
authors.lastname: Cukierman
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Cormier
authors.forename: Dimitri
authors.initials: D
authors.lastname: Lavillette
authors.forename: François-Loïc
authors.initials: FL
authors.lastname: Cosset
authors.forename: Tatjana
authors.initials: T
authors.lastname: Dragic
mesh_terms: D002460:Cell Line; D062445:Claudin-1; D057167:Claudins; D042783:Endothelial Cells / Q000821:virology; D020868:Gene Silencing; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000502:physiology*; D053586:Virus Internalization
chemical_list: C568108:CLDN1 protein, human; C524757:CLDN9 protein, human; D062445:Claudin-1; D057167:Claudins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D011991:Receptors, Virus; C122101:claudin 6