Novel evidence for the nucleocytoplasmic shuttling of HIV-1 Tat by Importin13

Abstract

Background HIV-1 encodes an essential regulatory protein, Tat which orchestrates viral gene expression from the HIV-1 promoter. Tat activity depends on Tat hijacking the nuclear transport system to gain access to the transcriptional machinery. The sole import factor identified for Tat to date, Importin b, directly interacts with Tat-NLS to mediate its active nuclear import. While Tat localises in the nucleoli & nucleoplasm of transformed cells, in HIV-1 infected primary T-cells, Tat accumulates at the plasma membrane, where it is secreted. The different subcellular accumulation of Tat could be due to selective enhancement of the nuclear import machinery in transformed cells or alternatively, an increase in Tat nuclear export or its specific cytosolic retention in primary T cells. Of note, Tat does not contain a classical NES and its nuclear export remains to be established. Here, we characterise the bidirectional transport receptor, Importin 13 (IPO13) as a novel transport receptor mediating the nucleo-cytoplasmic shuttling of Tat.