Figure 7.

A schematic model explaining the involvement of Rev in nucleocytoplasmic trafficking of IN in HIV-1 infected cells. In the cytoplasmic pre-integration complex, the IN molecules (red circle) are bound to viral DNA (double black lines) resulting in the formation of an IN-DNA complex. A certain amounts of the IN-DNA complexes are translocated into the nucleus (blue arrow) (I) (presumably up to 10 h PI) before sufficient amount of Rev molecules are synthesized. Binding of Rev molecules (green triangle) to the IN induces dissociation of the IN-DNA complex (magenta arrow) (II) and blocks nuclear import (orange blocked arrow) of the IN (III) (from 6 h PI). Within the nucleus, the IN is able to mediate integration of only one or two viral DNA molecules (black arrow) into the host genome (double brown line) (IV) (10–16 h PI). The IN of the remaining IN-DNA complexes interacts with the intranuclear Rev, thus blocking its enzymatic activity and consequently the integration process (red blocked arrow) (V). Similar to the cytoplasmic Rev also the intranuclear Rev molecules promote dissociation of the IN-DNA complex (green arrow) (VI) and mediate nuclear export of the free IN (brown arrow) (VII) (from 16 h PI).