A hallmark feature of lentiviruses, which separates them from other members of the retrovirus family, is their ability to infect non-dividing cells by traversing the nuclear pore complex. The viral determinant that mediates HIV-1 nuclear import is the viral capsid (CA) protein, which forms the conical core protecting the HIV-1 genome in a mature virion. Recently, a series of novel approaches developed to monitor post-fusion events in infection have challenged previous textbook models of the viral life cycle, which envisage reverse transcription and disassembly of the capsid core as events that complete in the cytoplasm. In this review, we summarize these recent findings and describe their implications on our understanding of the spatiotemporal staging of HIV-1 infection with a focus on the nuclear import and its implications in other aspects of the viral lifecycle.
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