Inhibition of lentiviral nuclear import pathways by Mx2

项目摘要/摘要 慢病毒，如HIV-1，在它们通过劫持感染未分裂细胞的能力方面是唯一有效的 细胞核质运输途径的一部分。灵长类慢病毒的核输入受到抑制 干扰素诱导的GTP酶MX2，定位于核孔复合体。然而，通过这个过程 HIV-1利用细胞核质转运，MX2如何抑制核进入仍然很差 已定义。此外，MX2与其他影响预整合的细胞蛋白的关系 HIV-1感染的不同阶段尚不清楚。我们之前已经证明了MX2的抗病毒活性 受细胞类型、细胞周期和HIV-1衣壳中核质运输途径的影响 依赖的态度。我们进一步确定MX2抑制非病毒货物的核质转运。 细胞类型依赖的方式，表明其在抗病毒干扰素应答中可能具有更广泛的功能。这里, 我们的目标是确定MX2是如何定位于核孔复合体的，核输入途径是 MX2的抑制作用、MX2在核质运输中的异质性以及MX2如何影响 HIV-1与其他抗病毒蛋白的相互作用。

PROJECT SUMMARY/ABSTRACT Lentiviruses such as HIV-1 are uniquely efficient in their ability to infect non-dividing cells through the hijacking of cellular nucleocytoplasmic trafficking pathways. Nuclear import of primate lentiviruses is inhibited by the interferon inducible GTPase Mx2, which localizes to the nuclear pore complex. However, the process by which HIV-1 utilizes cellular nucleocytoplasmic trafficking and how nuclear entry is inhibited by Mx2 remain poorly defined. Furthermore, the relationship between Mx2 and other cellular proteins that affect the pre-integration stages of HIV-1 infection is not understood. We have previously demonstrated that the antiviral activity of Mx2 is affected by cellular nucleocytoplasmic trafficking pathways in a cell-type, cell-cycle, and HIV-1 capsid- dependent manner. We further determined that Mx2 inhibits nucleocytoplasmic trafficking of non-viral cargo in a cell-type dependent manner, indicating that it may have broader functions in antiviral interferon responses. Here, we aim to determine how Mx2 is localized to the nuclear pore complex, the nuclear import pathways that are inhibited by Mx2, how Mx2 is affected be heterogeneity in nucleocytoplasmic trafficking, and how Mx2 affects the interaction of HIV-1 with other antiviral proteins.