Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes.
Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes.
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DOI：
10.1073/pnas.95.4.1758
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发表时间：
1998-02
影响因子：
11.1
通讯作者：
B. Sherry;G. Zybarth;M. Alfano;L. Dubrovsky;R. Mitchell;D. Rich;P. Ulrich;R. Bucala;A. Cerami;M. Bukrinsky
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文献类型：
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作者：
B. Sherry;G. Zybarth;M. Alfano;L. Dubrovsky;R. Mitchell;D. Rich;P. Ulrich;R. Bucala;A. Cerami;M. Bukrinsky
亲环蛋白是一种结合环孢素a （CsA）并具有肽基脯氨酸顺反异构酶活性的蛋白家族。此外，它们由活化的细胞分泌，并以细胞因子样的方式起作用，可能是通过细胞表面亲环蛋白受体的信号传导。最近，宿主源性亲环蛋白A （CyPA）已被证明可被整合到HIV-1病毒粒子中，其整合对病毒感染至关重要。在这里，我们提出证据支持病毒相关CyPA在HIV-1感染的早期事件中的作用。我们报道，HIV-1感染的初级外周血单个核细胞可以被抑制：(i)过量的外源性添加的CyPA；（ii） CsA类似物不能进入细胞；（iii）中和CyPA抗体。结合我们的观察结果，重组CyPA诱导永生化细胞和原代CD4+ T淋巴细胞中钙的动员，以及用碘化CyPA孵育T细胞，随后进行化学交联，导致在细胞表面形成高分子质量复合物，这些结果表明，hiv -1相关的CyPA通过与细胞受体的相互作用介导病毒感染的早期事件。这种相互作用可能成为抗艾滋病毒治疗和疫苗的靶点。
Cyclophilins are a family of proteins that bind cyclosporin A (CsA) and possess peptidyl-prolyl cis-trans isomerase activity. In addition, they are secreted by activated cells and act in a cytokine-like manner, presumably via signaling through a cell surface cyclophilin receptor. More recently, host-derived cyclophilin A (CyPA) has been shown to be incorporated into HIV-1 virions and its incorporation essential for viral infectivity. Here we present evidence supporting a role for viral-associated CyPA in the early events of HIV-1 infection. We report that HIV-1 infection of primary peripheral blood mononuclear cells can be inhibited by: (i) an excess of exogenously added CyPA; (ii) a CsA analogue unable to enter the cells; (iii) neutralizing antibodies to CyPA. Taken together with our observations that recombinant CyPA-induced mobilization of calcium in immortalized, as well as primary, CD4+ T lymphocytes, and that incubation of T cells with iodinated CyPA, followed by chemical cross-linking, resulted in the formation of a high molecular mass complex on the cell surface, these results suggest that HIV-1-associated CyPA mediates an early event in viral infection via interaction with a cellular receptor. This interaction may present a target for anti-HIV therapies and vaccines.