The activity of the human immunodeWciency virus (HIV)-1 Rev protein is essential for virus replication. Its subcellular localization is nucleolar, but it has the ability to shuttle continuously between the nucleus and the cytoplasm (Felber et al. 1989; Kalland et al. 1994) . Rev possesses both an NES and an NLS; the NLS is associated with importin-as well as with B23 (Fankhauser et al. 1991; Henderson and Percipalle 1997) . Rev-GFP movement in the nucleolus is very slow, implying that it is attached to aYnity binding sites in this subcellular compartment (Daelemans et al. 2004 ). In addition, the transport of Rev from the nucleolus to the cytoplasm can be aVected negatively by NF90, a cellular protein that colocalizes with Rev in the nucleolus (Urcuqui-Inchima et al. 2006) (Fig. 4) . This indicates that the transport of HIV transcripts by Rev to the cytoplasm is a regulated process. Because Rev is concentrated in the nucleolus, it was suggested that the passage of Rev to the nucleolus is an indispensable step for Rev function, and hence for HIV-1 replication. Indeed, based on HIV-1 RNA traYcking through the nucleolus, this organelle is an essential participant of HIV-1 RNA export (Michienzi et al. 2000) .