FIG 8.

Working model for multimerization-dependent NES masking in Rev's nucleocytoplasmic trafficking scheme. Our data suggest Rev-Rev interactions promote Rev's nucleolar accumulation by inhibiting CRM1 from accessing Rev's NES prior to and during nuclear import (left NPC, green arrows). An unmasked NES disrupts Rev's capacity to accumulate in the nucleolus by blocking nuclear import (red arrow in cytoplasm, SNES) or driving immediate export of Rev from the nucleus (red arrow in nucleus, NES). In the nucleus, one or more Rev NES peptides are likely exposed through an unknown mechanism during formation of Rev/RNA complexes, thus serving as a signal for the recruitment of CRM1 (right NPC, green arrows). Nuclear export and dissolution of the complex promotes recycling of Rev and downstream events in the HIV-1 life cycle.