The ability of TNPO3-depleted cells to inhibit HIV-1 infection requires CPSF6.
The ability of TNPO3-depleted cells to inhibit HIV-1 infection requires CPSF6.
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DOI：
10.1186/1742-4690-10-46
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发表时间：
2013-04-26
期刊：
影响因子：
3.3
通讯作者：
Diaz-Griffero F
中科院分区：
文献类型：
--
作者：
Fricke T;Valle-Casuso JC;White TE;Brandariz-Nuñez A;Bosche WJ;Reszka N;Gorelick R;Diaz-Griffero F
细胞核转运蛋白TNPO 3/transportin-SR 2/Tnp 3的表达是HIV-1感染所必需的。哺乳动物细胞中TNPO 3表达的耗竭在逆转录后但在整合前抑制HIV-1感染。这项工作探讨了切割和多聚腺苷酸化特异性因子亚基6（CPSF 6）在TNPO 3耗尽细胞抑制HIV-1感染的能力中的作用。我们的研究结果表明，TNPO 3表达的耗竭抑制HIV-1感染，而TNPO 3和CPSF 6表达的同时耗竭拯救HIV-1感染。进行了几个实验以了解CPSF 6对感染性的拯救。我们的实验显示，与来自野生型细胞的CPSF 6相比，来自TNPO 3耗尽细胞的内源性表达的CPSF 6的HIV-1衣壳结合能力没有改变。与我们以前的结果一致，TNPO 3的耗尽并没有改变CPSF 6的核定位。对HIV-1感染期间2-LRT环形成的研究表明，TNPO 3耗尽的细胞在整合过程中受损或在2-LTR环形成中表现出缺陷。为了了解CPSF 6的胞质部分是否负责TNPO 3耗尽细胞中的HIV-1抑制，我们测试了胞质全长CPSF 6阻断HIV-1感染的能力。这些结果表明，胞浆全长CPSF 6的过表达可以在核输入步骤中阻断HIV-1感染。衣壳测定的命运揭示了CPSF 6的胞质表达增强了感染期间HIV-1核心的稳定性。这些结果表明TNPO 3耗尽的细胞对HIV-1的抑制需要CPSF 6。
Expression of the cellular karyopherin TNPO3/transportin-SR2/Tnp3 is necessary for HIV-1 infection. Depletion of TNPO3 expression in mammalian cells inhibits HIV-1 infection after reverse transcription but prior to integration. This work explores the role of cleavage and polyadenylation specificity factor subunit 6 (CPSF6) in the ability of TNPO3-depleted cells to inhibit HIV-1 infection. Our findings showed that depletion of TNPO3 expression inhibits HIV-1 infection, while the simultaneous depletion of TNPO3 and CPSF6 expression rescues HIV-1 infection. Several experiments to understand the rescue of infectivity by CPSF6 were performed. Our experiments revealed that the HIV-1 capsid binding ability of the endogenously expressed CPSF6 from TNPO3-depleted cells does not change when compared to CPSF6 from wild type cells. In agreement with our previous results, depletion of TNPO3 did not change the nuclear localization of CPSF6. Studies on the formation of 2-LRT circles during HIV-1 infection revealed that TNPO3-depleted cells are impaired in the integration process or exhibit a defect in the formation of 2-LTR circles. To understand whether the cytosolic fraction of CPSF6 is responsible for the inhibition of HIV-1 in TNPO3-depleted cells, we tested the ability of a cytosolic full-length CPSF6 to block HIV-1 infection. These results demonstrated that overexpression of a cytosolic full-length CPSF6 blocks HIV-1 infection at the nuclear import step. Fate of the capsid assays revealed that cytosolic expression of CPSF6 enhances stability of the HIV-1 core during infection. These results suggested that inhibition of HIV-1 by TNPO3-depleted cells requires CPSF6.
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