Competitive binding of cleavage factors facilitates the translocation of an intact HIV-1 capsid through the nuclear pore complex

Recent experiments on HIV-1 have uncovered the translocation of an intact HIV-1 capsid through the nuclear pore complex (NPC) with the capsid disassembly occurring only within the nucleus near the integration site. How the HIV-1 capsid of diameter ~60 nm overcomes the steric barriers created by a dense arrangement of NPC proteins within the nuclear pore which is barely larger than the capsid is still an open question. Here, we address this question with an analytical model that accounts for the capsid geometry and its interactions with the NPC proteins. We show how the capsid docking to the pore is energetically favorable if the capsid's narrow end enters first. However, narrow-end-first entry alone is insufficient for the capsid's complete nuclear import, which critically requires a cleavage factor (CPSF6) concentration within the nucleus. Our results show how, with an increasing CPSF6 concentration within the nucleus, capsid translocation speeds up, while the capsid remains stalled near the nucleus if CPSF6 is depleted. Our results are in agreement with recent experimental results and shed light on the critical factors that govern intact viral entry into the nucleus.