Significance of palmitoylation of CD81 on its association with tetraspanin-enriched microdomains and mediating hepatitis C virus cell entry
Significance of palmitoylation of CD81 on its association with tetraspanin-enriched microdomains and mediating hepatitis C virus cell entry
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CD81 的棕榈酰化对其与富含四跨膜蛋白的微结构域和介导丙型肝炎病毒细胞进入的关联的意义。
DOI：
10.1016/j.virol.2012.03.002
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发表时间：
2012-08-01
期刊：
影响因子：
3.7
通讯作者：
Qi, Zhong-Tian
中科院分区：
文献类型：
--
作者：
Zhu, Yong-Zhe;Luo, Yuan;Qi, Zhong-Tian
CD81 是丙型肝炎病毒 (HCV) 的共同受体，是四跨膜蛋白超家族的成员，在近膜半胱氨酸残基中被严重棕榈酰化。棕榈酰化在蛋白质-蛋白质相互作用以及与富含胆固醇的膜结构域的关联中发挥着重要作用。在本研究中，生成了表达野生型或棕榈酰化缺陷型 CD81 的 Huh7 细胞，以分析 CD81 的棕榈酰化是否参与 HCV 细胞进入。我们的数据表明，CD81 的去棕榈酰化显着降低了其与四跨膜蛋白 CD151 的关联，但不影响 CD81 在耐洗涤剂膜中的分配。此外，去棕榈酰化的CD81降低了宿主细胞对HCV的易感性。值得注意的是，CD151特异性抗体和siRNA抑制HCV细胞进入，并且CD81与CD151的分离减少了病毒颗粒/CD81复合物向细胞-细胞接触区域的横向移动。这些结果表明，CD81 的棕榈酰化至少部分是通过调节 CD81 与富含四跨膜蛋白的微结构域的关联来促进 HCV 进入。 (C) 2012 Elsevier Inc. 保留所有权利。
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. (C) 2012 Elsevier Inc. All rights reserved.