Tetraspanin CD63 is a regulator of HIV-1 replication.
Tetraspanin CD63 is a regulator of HIV-1 replication.
复制标题
四跨膜蛋白 CD63 是 HIV-1 复制的调节因子。
DOI：
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发表时间：
2015
影响因子：
1.4
通讯作者：
X. Bai
中科院分区：
文献类型：
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作者：
Enqing Fu;L. Pan;Yonghong Xie;D. Mu;W. Liu;F. Jin;X. Bai
巨噬细胞和CD 4（+）T细胞是HIV-1感染的主要宿主。CD 63是一种四跨膜蛋白，已被证明在巨噬细胞中HIV-1复制过程中发挥重要作用。在这项研究中，我们进一步证实了在原代人CD 4（+）T细胞、树突状细胞和CD 4（+）细胞系中HIV-1复制事件中CD 63的需要。最有趣的是，我们还显示了共聚焦显微镜和免疫共沉淀实验的证据，CD 63和HIV-1的主要受体CD 4在原代人巨噬细胞和CD 4（+）细胞系的共定位和内化。分析显示，CD 63耗尽的CD 4（+）T细胞，树突状细胞和细胞系显示HIV-1的产生显著减少。进一步的分析表明，CD 63下调减少了早期HIV蛋白达特的产生，并通过CD 63-Gag相互作用影响HIV蛋白Gag。与此一致，CD 63沉默也抑制了晚期蛋白p24的产生。此外，我们揭示了CD 63沉默对具有广泛病毒攻击（MOI > 0.2）的HIV-1复制没有影响。这些结果表明，CD 63在HIV-1感染的早期和晚期（MOI < 0.2）起双重作用。
Macrophages and CD4(+) T-cells are the major reservoirs for HIV-1 infection. CD63 is a tetraspanin transmembrane protein, which has been shown to play an essential role during HIV-1 replication in macrophages. In this study, we further confirm the requirement of CD63 in HIV-1 replication events in primary human CD4(+) T-cells, dendritic cells, and a CD4(+) cell line. Most interestingly, we also show the evidences for the co-localization and internalization of CD63 and HIV-1 major receptor CD4 in primary human macrophages and CD4(+) cell line by confocal microscopy and Co-Immunoprecipitation assay. Analysis revealed that CD63-depleted CD4(+) T-cells, dendritic cells, and a cell line showed significant decrease in HIV-1 production. Further analysis showed that CD63 down regulation reduced production of the early HIV protein Tat, and affected HIV protein Gag by CD63-Gag interaction. In agreement, CD63 silencing also inhibited production of the late protein p24. Furthermore, we revealed that CD63 silencing has no effect on HIV-1 replication with extensive viral challenge (MOI > 0.2). These findings suggest that CD63 plays a dual-role both in early and late HIV-1 life cycle with a range of HIV-1 infection (MOI < 0.2).