HIV-1 accesses the nuclear DNA of interphase cells via a poorly defined process involving functional interactions between the capsid protein (CA) and nucleoporins (Nups). Here, we show that HIV-1 CA can bind multiple Nups, and that both natural and manipulated variation in Nup levels impacts HIV-1 infection in a manner that is strikingly dependent on cell-type, cell-cycle, and cyclophilin A (CypA). We also show that Nups mediate the function of the antiviral protein MX2, and that MX2 can variably inhibit non-viral NLS function. Remarkably, both enhancing and inhibiting effects of cyclophilin A and MX2 on various HIV-1 CA mutants could be induced or abolished by manipulating levels of the Nup93 subcomplex, the Nup62 subcomplex, NUP88, NUP21, RANBP2, or NUP153. Our findings suggest that several Nup-dependent 'pathways' are variably exploited by HIV-1 to target host DNA in a cell-type, cell-cycle, CypA and CA-sequence dependent manner, and are differentially inhibited by MX2.

HIV-1通过一个衣壳蛋白（CA）与核孔蛋白（Nups）之间的功能性相互作用的定义不明确的过程访问相间细胞的核DNA。在这里，我们证明HIV-1 CA可以结合多个Nups，并且Nup水平的自然变化和受控变化都以显着依赖于细胞类型，细胞周期和亲环蛋白A（CypA）的方式影响HIV-1感染。 ）。我们还显示，Nups介导抗病毒蛋白MX2的功能，并且MX2可以可变地抑制非病毒NLS功能。值得注意的是，通过控制Nup93亚复合物，Nup62亚复合物，NUP88，NUP21，RANBP2或NUP153的水平，可以诱导或废除亲环蛋白A和MX2对各种HIV-1 CA突变体的增强和抑制作用。我们的发现表明，有几种依赖于Nup的“途径”