115 HIV-1 Rev and Regulation of Rev Nucleo-Cytoplasmic Shuttling
JAIDS Journal of Acquired Immune Deficiency Syndromes:
Centre for Research in Infectious Diseases, University College Dublin, Dublin, Ireland
The HIV-1 regulatory protein Rev is essential for viral replication and mediates the nuclear export of unspliced viral transcripts, a process that requires active nucleocytoplasmic shuttling. Rev nuclear import is facilitated by the recognition of its nuclear localisation signal (NLS) by a number of import factors, which include importin β and transportin. However it is unclear which nuclear import pathway(s) predominate in vivo, and whether other specific cellular factors can modulate Rev shuttling. In this study we have demonstrated an interaction of the cellular protein HIC (Human I-mfa domain-Containing protein) with Rev. It could be shown that HIC interferes with the Rev NLS - importin β interaction and inhibits nuclear import. In contrast HIC does not affect transportin mediated Rev nuclear import, suggesting that Rev-NLS recognition by the various import factors may involve distinct mechanisms. Our findings suggest that the cytoplasmic sequestration of Rev by HIC is one mechanism for the regulation of Rev function, and that the employment of different import factors by Rev enables the protein to change its nuclear trafficking strategy depending on the cellular environment.© 2011 Lippincott Williams & Wilkins, Inc.