The human I-mfa domain containing protein, HIC, interacts with HIV-1 Tat and Rev and sequesters them in the cytoplasm

Tat and Rev are equally critical for HIV-1 replication and work in a sequential manner: first, transactivation of the HIV-1 LTR by Tat, followed by nuclear export of partially spliced and unspliced viral transcripts by Rev. Both functions require Tat and Rev to be imported to the nucleus, a process mediated by molecular recognition of their homologous arginine-rich NLS domains by importin-β.

Here, we report the interaction of the human I-mfa domain containing protein, HIC, with Tat and Rev resulting in the cytoplasmic redistribution of Tat and Rev with a concomitant reduction in their nuclear accumulation. We will discuss our data resulting from colocalisation studies and competitive in vitro nuclear import assays, which collectively support a model where HIC would mask Tat and Rev NLS domains, thereby impairing their nuclear import via rendering the NLS inaccessible to importin-β.

Functionally, this cytoplasmic sequestration could appear to represent a novel mechanism for the control of Tat and Rev activities and ultimately the regulation of HIV-1 replication.