title: Lipoprotein Receptors Redundantly Participate in Entry of Hepatitis C Virus.
abstract: Scavenger receptor class B type 1 (SR-B1) and low-density lipoprotein receptor (LDLR) are known to be involved in entry of hepatitis C virus (HCV), but their precise roles and their interplay are not fully understood. In this study, deficiency of both SR-B1 and LDLR in Huh7 cells was shown to impair the entry of HCV more strongly than deficiency of either SR-B1 or LDLR alone. In addition, exogenous expression of not only SR-B1 and LDLR but also very low-density lipoprotein receptor (VLDLR) rescued HCV entry in the SR-B1 and LDLR double-knockout cells, suggesting that VLDLR has similar roles in HCV entry. VLDLR is a lipoprotein receptor, but the level of its hepatic expression was lower than those of SR-B1 and LDLR. Moreover, expression of mutant lipoprotein receptors incapable of binding to or uptake of lipid resulted in no or slight enhancement of HCV entry in the double-knockout cells, suggesting that binding and/or uptake activities of lipid by lipoprotein receptors are essential for HCV entry. In addition, rescue of infectivity in the double-knockout cells by the expression of the lipoprotein receptors was not observed following infection with pseudotype particles bearing HCV envelope proteins produced in non-hepatic cells, suggesting that lipoproteins associated with HCV particles participate in the entry through their interaction with lipoprotein receptors. Buoyant density gradient analysis revealed that HCV utilizes these lipoprotein receptors in a manner dependent on the lipoproteins associated with HCV particles. Collectively, these results suggest that lipoprotein receptors redundantly participate in the entry of HCV.
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Takasuke
authors.initials: T
authors.lastname: Fukuhara
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Ono
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Uemura
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Kawachi
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Shiokawa
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mori
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Wada
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Shima
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiraga
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
mesh_terms: D002460:Cell Line; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D016133:Polymerase Chain Reaction; D011973:Receptors, LDL / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: C573412:LDLR protein, human; D011973:Receptors, LDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B