Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion
Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion
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DOI：
10.4049/jimmunol.177.8.5129
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发表时间：
2006-10-15
影响因子：
4.4
通讯作者：
Sanchez-Madrid, Francisco
中科院分区：
文献类型：
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作者：
Gordon-Alonso, Monica;Yanez-Mo, Maria;Sanchez-Madrid, Francisco
靶细胞膜上的蛋白质组织可能调节HIV-1的传播。由于四联蛋白CD81与HIV-1包膜蛋白受体CD4 （Env; gp120/gp41）相关，我们已经探索了这种分子可能调节HIV-1感染初始步骤的可能性。另一方面，CD81属于四白蛋白家族，该家族被描述为质膜上蛋白质微结构域的组织者。因此，我们研究了CD81和其他相关的四联蛋白CD9在HIV-1介导的细胞间融合过程中的作用。我们发现抗tetraspanin抗体增强了HIV-1包膜蛋白诱导的合胞体形成和病毒进入人T淋巴细胞。此外，抗cd81抗体触发其在补丁中聚集，其中包括CD4和CXCR4。此外，CD81和CD9表达的下调导致合胞体形成和病毒进入的增加。因此，CD81和CD9的过表达使细胞对环境介导的合胞体形成不那么敏感。这些数据表明CD9和CD81在HIV-1包膜诱导的膜融合中起重要作用。
Protein organization on the membrane of target cells may modulate HIV-1 transmission. Since the tetraspanin CD81 is associated to CD4, the receptor of HIV-1 envelope protein (Env; gp120/gp41), we have explored the possibility that this molecule may modulate the initial steps of HIV-1 infection. On the other hand, CD81 belongs to the tetraspanin family, which has been described as organizers of protein microdomains on the plasma membrane. Therefore, the role of CD81 and other related tetraspanin, CD9, on the cell-to-cell fusion process mediated by HIV-1 was studied. We found that anti-tetraspanin Abs enhanced the syncytia formation induced by HIV-1 envelope proteins and viral entry in human T lymphoblasts. In addition, anti-CD81 Abs triggered its clustering in patches, where CD4 and CXCR4 were included. Moreover, the knocking down of CD81 and CD9 expression resulted in an increase in syncytia formation and viral entry. Accordingly, overexpression of CD81 and CD9 rendered cells less susceptible to Env-mediated syncytia formation. These data indicate that CD9 and CD81 have an important role in membrane fusion induced by HIV-1 envelope.