“…The pre-integration complex (PIC) has a mass of several million Daltons and a Stokes radius of 20-30 nm (it is roughly equivalent to or greater in size than a eukaryotic ribosome), so it is clear that, in directing import of this structure though the nuclear pore (Figure 1), lentiviruses have evolved to surmount a substantial problem (reviewed in [101][102][103]). For HIV-1, considerable evidence has been put forward for nuclear import determinants in virion proteins [98,99], and, more recently, for a role for a central plus-strand discontinuity, or flap [104], found in the PIC [61,105,106]. Retroviral (−)strand synthesis generates a (+)RNA/ (−)DNA duplex [107].…”