Significance of palmitoylation of CD81 on its association with tetraspanin-enriched microdomains and mediating hepatitis C virus cell entry

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• 作者：Yong-Zhe Zhu¹ ; Yuan Luo¹ ; Ming-Mei Cao¹ ; Yuan Liu ; Xiao-Qing Liu ; Wen Wang ; Da-Ge Wu ; Mo Guan ; Qing-Qiang Xu ; Hao Ren ; Ping Zhao ; ^{pnzhao@163.com} ; Zhong-Tian Qi ; ^{qizt@smmu.edu.cn}
• 关键词：Hepatitis C virus ; CD81 ; Palmitoylation ; Tetraspanin-enriched microdomains ; Cell entry
• 刊名：Virology
• 出版年：2012
• 期刊代码：108_00426822
• 类别：imm
• 出版时间：1 August, 2012
• 卷：429
• 期：2
• 页码：112-123
• 文件大小：2557 K

摘要

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.