Cyclophilin interactions with incoming human immunodeficiency virus type 1 capsids with opposing effects on infectivity in human cells
Cyclophilin interactions with incoming human immunodeficiency virus type 1 capsids with opposing effects on infectivity in human cells
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DOI：
10.1128/jvi.79.1.176-183.2005
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发表时间：
2005-01-01
影响因子：
5.4
通讯作者：
Bieniasz, PD
中科院分区：
文献类型：
--
作者：
Hatziioannou, T;Perez-Caballero, D;Bieniasz, PD
亲环蛋白A （CypA）是一种肽基脯氨酸异构酶，与人类免疫缺陷病毒1型（HIV-1）的衣壳蛋白（CA）结合，并通过这样做促进HIV-1的复制。尽管在病毒粒子组装过程中，CypA通过CypA- gag相互作用被整合到HIV-1病毒粒子中，但在本研究中，我们发现在病毒衣壳进入靶细胞后发生的CypA- ca相互作用是CypA影响HIV-1复制的主要决定因素。具体来说，通过使用正常和缺乏CypA的Jurkat细胞，我们证明CypA存在于靶细胞而不是产生病毒的细胞中，增强了HIV-1的感染性。此外，CypA- ca与环孢素A （CsA）相互作用的破坏仅在靶细胞表达CypA时才能抑制HIV-1的感染性。CsA对人类细胞HIV-1感染的影响取决于使用哪种特定的细胞系作为靶点，而赋予CsA抗性和依赖性的CA突变只有在靶细胞（而不是产病毒细胞）接受CsA处理时才会发挥作用。CsA在不同人类细胞中对HIV-1感染的不同影响似乎不是由最近描述的逆转录病毒限制因子trim5 α的多态性引起的。我们推测CypA和/或CypA相关蛋白直接或通过调节与未知宿主细胞因子的相互作用影响传入HIV-1衣壳的命运。
Cyclophilin A (CypA) is a peptidyl-prolyl isomerase that binds to the capsid protein (CA) of human immunodeficiency virus type 1 (HIV-1) and by doing so facilitates HIV-1 replication. Although CypA is incorporated into HIV-1 virions by virtue of CypA-Gag interactions that occur during virion assembly, in this study we show that the CypA-CA interaction that occurs following the entry of the viral capsid into target cells is the major determinant of CypA's effects on HIV-1 replication. Specifically, by using normal and CypA-deficient Jurkat cells, we demonstrate that the presence of CypA in the target and not the virus-producing cell enhances HIV-1 infectivity. Moreover, disruption of the CypA-CA interaction with cyclosporine A (CsA) inhibits HIV-1 infectivity only if the target cell expresses CypA. The effect of CsA on HIV-1 infection of human cells varies according to which particular cell line is used as a target, and CA mutations that confer CsA resistance and dependence exert their effects only if target cells, and not if virus-producing cells, are treated with CsA. The differential effects of CsA on HIV-1 infection in different human cells appear not to be caused by polymorphisms in the recently described retrovirus restriction factor TRIM5alpha. We speculate that CypA and/or CypA-related proteins affect the fate of incoming HIV-1 capsid either directly or by modulating interactions with unidentified host cell factors.