Multiple importins function as nuclear transport receptors for the rev protein of human immunodeficiency virus type 1

Abstract

The Rev protein of human immunodeficiency virus type 1 is an RNA-binding protein that is required for nuclear export of unspliced and partially spliced viral mRNAs. Nuclear import of human immunodeficiency virus type 1 Rev has been suggested to depend on the classic nuclear transport receptor importin β, but not on the adapter protein importin α. We now show that, similar to importin α, Rev is able to dissociate RanGTP from recycling importin β, a reaction that leads to the formation of a novel import complex. Besides importin β, the transport receptors transportin, importin 5, and importin 7 specifically interact with Rev and promote its nuclear import in digitonin-permeabilized cells. A single arginine-rich nuclear localization sequence of Rev is required for interaction with all importins tested so far. In contrast to the importin β-binding domain of importin α, Rev interacts with an N-terminal fragment of importin β. Transportin contains two independent binding sites for Rev. Hence, the mode of interaction of importin β and transportin with Rev is clearly distinct from that with their classic import cargoes. Taken together, the viral protein takes advantage of multiple cellular transport pathways for its nuclear accumulation. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.