(A) The early phase of the retroviral lifecycle is divided into nine steps, spanning from step 1, when the extracellular virus initially engages its cellular receptor, to step 9, with the completion of provirus formation. Steps 5–8, which encompass IN 3′ processing of the nascent reverse transcript in the cytoplasm to the formation of the DNA strand transfer reaction product in the nucleus (highlighted in blue font), could potentially be affected by the IN–LEDGF/p75 interaction. Among these steps, lentiviruses display unique nuclear import and chromatin targeting properties (blue boxes). (B) Details of phosphodiester bond breakage and joining during HIV-1 integration. Small vertical arrows denote the bonds cleaved by IN, using water as the chemical nucleophile for 3′ processing, and the OH groups at the 3′ ends of the processed viral DNA for DNA strand transfer [4]. Results of in vitro experiments indicate that a dimer of HIV-1 IN suffices to process each viral DNA end, whereas a tetramer is required for DNA strand transfer activity [92]–[94]. IN is known to function as a multimer during infection [95],[96]; notably, though, its functional PIC-associated multimeric form has not been determined. A tetramer is represented at each step here for simplicity. The open and filled triangles at the ends of the viral DNA represent U3 and U5 sequences, respectively, important for IN function (reviewed in [97]). Host cell factors are likely to repair the single strand gaps present within the DNA recombination intermediate (reviewed in [5]).