title: Significance of palmitoylation of CD81 on its association with tetraspanin-enriched microdomains and mediating hepatitis C virus cell entry.
abstract: CD81, a co-receptor for hepatitis C virus (HCV), is a member of the tetraspanin superfamily and is heavily palmitoylated in the juxtamembrane cysteine residues. Palmitoylation plays an important role in protein-protein interactions and association with cholesterol-rich domains of membranes. In this study, Huh7 cells expressing wild-type or palmitoylation-defective CD81 were generated to analyze whether palmitoylation of CD81 is involved in HCV cell entry. Our data showed that de-palmitoylation of CD81 dramatically reduced its association with tetraspanin CD151, but did not influence CD81 partition in detergent-resistant membranes. Moreover, de-palmitoylated CD81 decreased the host cell susceptibility to HCV. Notably, CD151-specific antibodies and siRNA inhibited HCV cell entry, and detachment of CD81 with CD151 decreased the lateral movement of virus particle/CD81 complex to areas of cell-cell contact. These results suggest that palmitoylation of CD81 should facilitate HCV entry, at least in part, by regulating the association of CD81 with tetraspanin-enriched microdomains.
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yong-Zhe
authors.initials: YZ
authors.lastname: Zhu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Luo
authors.forename: Ming-Mei
authors.initials: MM
authors.lastname: Cao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Da-Ge
authors.initials: DG
authors.lastname: Wu
authors.forename: Mo
authors.initials: M
authors.lastname: Guan
authors.forename: Qing-Qiang
authors.initials: QQ
authors.lastname: Xu
authors.forename: Hao
authors.initials: H
authors.lastname: Ren
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.forename: Zhong-Tian
authors.initials: ZT
authors.lastname: Qi
mesh_terms: D002460:Cell Line; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D054878:Lipoylation; D021962:Membrane Microdomains / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011991:Receptors, Virus / Q000378:metabolism*; D060225:Tetraspanin 28 / Q000378:metabolism*; D059470:Tetraspanins / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: C554798:CD81 protein, human; D011991:Receptors, Virus; D060225:Tetraspanin 28; D059470:Tetraspanins