Lipoprotein Receptors Redundantly Participate in Entry of Hepatitis C Virus

PLoS Pathogens

Kazuaki Chayama¹  Nobuhiko Hiraga¹  Toru Okamoto²  Masami Wada²  Yukako Kawachi²  Takasuke Fukuhara²  Kentaro Uemura²  Mai Shiokawa²  Chikako Ono²  Hiroyuki Mori²  Satomi Yamamoto²  Yoshiharu Matsuura²  Ryoichi Shima²  Ryosuke Suzuki³  Takaji Wakita³ 

[1] Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan;Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan;Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan

关键词: Hepatitis C virus;    Lipoprotein receptors;    Lipids;    Immunoblotting;    Lipoproteins;    Small interfering RNAs;    Cell binding;    Vector-borne diseases;   

DOI  :  10.1371/journal.ppat.1005610

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY