Figure 9.

An updated model for HIV-1 intracellular transport and DNA Flap-dependent nuclear import. (1) HIV-1 viruses enter target cells by receptor-mediated fusion and need to cross and/or interact with the actin cortex underlying the plasma membrane for productive infection to take place (Campbell et al, 2004). Post-fusion uncoating does not take place at this stage. (2) HIV-1 RTCs proceeding directly from the core of the particle undergo rapid and saltatory microtubule-directed movement towards the nuclear compartment (McDonald et al, 2002; Arhel et al, 2006b). (3) RTCs undergo transition from microtubules onto actin filaments at close proximity to the nuclear compartment and then (4) slow actin-directed movements towards the nuclear membrane (Arhel et al, 2006b). (5) HIV-1 CAs containing viral genome dock at NPCs. Interaction with cytoplasmic filaments emanating from NPCs is hypothetical. (6) As docking of RTCs at the nuclear pore is more rapid than RT°, we surmise that most of viral DNA synthesis occurs within an integral CA core docked at the NPC. Upon RT° completion and formation of the central DNA Flap, which is consequent upon the final strand displacement event, (7) docked RTCs can undergo DNA-Flap-dependent maturation, leading to PIC formation lacking the CA shell. Complexes that lack DNA Flap formation accumulate within intact HIV-1 CAs that forbid translocation through the nuclear pore. (8) The HIV-1 PIC is translocated through the nuclear pore. The folded structure of the PIC via integrase dimerization is hypothetical (Zennou et al, 2000). (9) The HIV-1 PIC undergoes a poorly characterized diffusive intranuclear transport (Arhel et al, 2006b) and (10) either integrates into host cell chromatin or circularizes into 1- or 2-LTR circles.