Cyclophilin B enhances HIV-1 infection.
Cyclophilin B enhances HIV-1 infection.
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DOI：
10.1016/j.virol.2015.12.015
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发表时间：
2016-02
期刊：
影响因子：
3.7
通讯作者：
Belshan M
中科院分区：
文献类型：
--
作者：
DeBoer J;Madson CJ;Belshan M
亲环素B（CypB）是亲免素家族的成员和细胞内伴侣。它主要定位于ER，但也含有核定位信号并从细胞分泌。CypB已被证明与人类免疫缺陷1型（HIV-1）的Gag蛋白相互作用。一些蛋白质组学和遗传学研究将其确定为参与HIV复制的潜在因子。在此，我们表明CypB的过度表达通过增加病毒DNA的核输入来增强HIV感染。这种增强不受环孢菌素处理的影响，需要蛋白质的N-末端。N-末端含有ER前导序列，推定的核定位信号，并且是分泌所需的。N-末端的缺失导致从ER的错误定位和HIV感染的抑制。被动转移实验表明，分泌的CypB不影响HIV感染。结合起来，这些实验表明，细胞内CypB调节HIV核输入的途径。
Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import.