HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection.
HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection.
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DOI：
10.1101/gad.12.2.175
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发表时间：
1998-01
影响因子：
10.5
通讯作者：
Marie A. Vodicka;D. Koepp;P. Silver;M. Emerman
中科院分区：
文献类型：
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作者：
Marie A. Vodicka;D. Koepp;P. Silver;M. Emerman
HIV-1 Vpr促进病毒核酸进入非分裂巨噬细胞的细胞核，并引起G2细胞周期阻滞。与它在核运输中的作用一致，我们发现Vpr在人和酵母细胞中都定位于核膜。与核输入受体的进口蛋白- β亚基一样，Vpr也与酵母进口蛋白- α亚基和核孔蛋白相互作用。此外，酵母中Vpr或importin- β的过表达会阻断mrna的核转运。Vpr的突变形式（Vpr F34I）不定位于核膜，也不与进口蛋白和核孔蛋白结合，使HIV-1无法有效感染巨噬细胞。然而，Vpr F34I仍然引起G2阻滞，这表明Vpr的双重功能在遗传上是可分离的。我们的数据表明Vpr在功能上类似于HIV-1预整合复合体的核输入中的importin-beta，这一功能对于Vpr在巨噬细胞感染中的作用至关重要，但不是G2阻滞。
HIV-1 Vpr promotes nuclear entry of viral nucleic acids in nondividing macrophages and also causes a G2 cell-cycle arrest. Consistent with its role in nuclear transport, we show Vpr localizes to the nuclear envelope in both human and yeast cells. Like the importin-beta subunit of the nuclear import receptor, Vpr also interacts with the yeast importin-alpha subunit and nucleoporins. Moreover, overexpression of either Vpr or importin-beta in yeast blocks nuclear transport of mRNAs. A mutant form of Vpr (Vpr F34I) that does not localize at the nuclear envelope, or bind to importin-alpha and nucleoporins, renders HIV-1 incapable of infecting macrophages efficiently. Vpr F34I, however, still causes a G2 arrest, demonstrating that the dual functions of Vpr are genetically separable. Our data suggest Vpr functionally resembles importin-beta in nuclear import of the HIV-1 pre-integration complex and this function is essential for the role of Vpr in macrophage infection, but not G2 arrest.